Pediatric Board Review CoursePediatric Board Review CoursePediatric Hematology/OncologyPediatric Hematology/Oncology

Kusum Viswanathan, MDKusum Viswanathan, MDVice Chair, Dept of PediatricsVice Chair, Dept of Pediatrics

Brookdale Univ Hospital and Medical CenterBrookdale Univ Hospital and Medical Center

Case 1Case 1

6 week old term infant 6 week old term infant refd for anemia. Hb 7.5, refd for anemia. Hb 7.5, Retic 2 %. Mother O+, Retic 2 %. Mother O+, Baby A -, Direct Coombs Baby A -, Direct Coombs +, Cord blood Hb 14.2 +, Cord blood Hb 14.2 g/dL. Jaundice of g/dL. Jaundice of 15mg/dL at 48 hours of 15mg/dL at 48 hours of life, recd photo Rx and life, recd photo Rx and discharged at 5 days. No discharged at 5 days. No complaints, pale, Bili 3.5, complaints, pale, Bili 3.5, Direct 0.5. Direct 0.5.

Blood smear shows Blood smear shows spherocytesspherocytes

Most likely Most likely explanantion:explanantion:

1.1. Rh hemolytic Rh hemolytic diseasedisease

2.2. G 6 PD deficiencyG 6 PD deficiency

3.3. Hereditary Hereditary spherocytosisspherocytosis

4.4. Physiologic anemiaPhysiologic anemia

5.5. ABO incompatibiltyABO incompatibilty

Newborn -anemiaNewborn -anemia

Hemoglobin at birth is 17 g/dl, MCV over Hemoglobin at birth is 17 g/dl, MCV over 100.100.Falls to 11-12 by 6 weeks of age- nadir.Falls to 11-12 by 6 weeks of age- nadir.Erythropoietin production shifts from liver to kidneys and Erythropoietin production shifts from liver to kidneys and reduces because of increase in PaO2.reduces because of increase in PaO2.Anemia at birth could be :Anemia at birth could be :– May not have equilibrated- May not have equilibrated- repeatrepeat– Hemorrhage, may not have had time to mount a retic responseHemorrhage, may not have had time to mount a retic response– Acute hemorrhage- pallor and tachypneaAcute hemorrhage- pallor and tachypnea– Look at MCV- Look at MCV- low MCV-suggestivelow MCV-suggestive of of

chronic feto-maternal hemorrhage chronic feto-maternal hemorrhage Alpha Thalassemia trait.Alpha Thalassemia trait.

– Kleihauer-Betke- Hb F resistance to acid elutionKleihauer-Betke- Hb F resistance to acid elution

Newborn-ThrombocytopeniaNewborn-Thrombocytopenia

A newborn has a completely normal physical exam A newborn has a completely normal physical exam except for a few petechiae. Platelet 50,000.except for a few petechiae. Platelet 50,000.Differential diagnosis:Differential diagnosis:– Production defects: Production defects:

TAR, Magakaryocytic hypoplasia, Trisomy 13, 18.TAR, Magakaryocytic hypoplasia, Trisomy 13, 18.Wiskott-Aldrich(small plt, X-linked, Ezcema , SCT cure) Wiskott-Aldrich(small plt, X-linked, Ezcema , SCT cure) Infections- viral, bacterial, Infiltration (Gauchers, Niemann Infections- viral, bacterial, Infiltration (Gauchers, Niemann Paick, Leukemia)Paick, Leukemia)

– Destruction: Destruction: Allo-immune- Platelet group incompatibiltyAllo-immune- Platelet group incompatibiltyAuto-immune: Mat ITP, Drugs (thiazide, tolbutamide), SLEAuto-immune: Mat ITP, Drugs (thiazide, tolbutamide), SLEInfections: CMV, Rubella, herpes, DICInfections: CMV, Rubella, herpes, DICLoss: Kasabach- Merritt syndrome (hemangiomas, DIC- Rx Loss: Kasabach- Merritt syndrome (hemangiomas, DIC- Rx DIC and hemangioma with Steroids, interferon, VCR)DIC and hemangioma with Steroids, interferon, VCR)

Immune thrombocytopeniaImmune thrombocytopenia

Auto-immune: Pregnant women with ITP/Hx of ITP Auto-immune: Pregnant women with ITP/Hx of ITP – Passive transfer of antibodies (IgG) from mother. Passive transfer of antibodies (IgG) from mother. – Even when mother has a normal platelet count (Splenectomy)Even when mother has a normal platelet count (Splenectomy)– Nadir-few days; Platelets < 50,00 have 1% risk of ICH.Nadir-few days; Platelets < 50,00 have 1% risk of ICH.– IVIG to mother, Fetal platelet counts, C sec, US, IVGG to babyIVIG to mother, Fetal platelet counts, C sec, US, IVGG to baby

Iso-Immune: Normal platelet count in motherIso-Immune: Normal platelet count in mother– Similar to Rh disease; PL A1 antigen/ Zw a negative mother.Similar to Rh disease; PL A1 antigen/ Zw a negative mother.– 97% of population is PL A 1 positive97% of population is PL A 1 positive– Sensitization early in pregnancySensitization early in pregnancy– Plt function defect because Anti-PL A1 interferes w/aggregation.Plt function defect because Anti-PL A1 interferes w/aggregation.– Severe bleeding more likely; first born affected; Severe bleeding more likely; first born affected; – Recovery in 2-3 weeksRecovery in 2-3 weeks– Mother’s washed (PLA1 neg) platelets; IVIG; Ultrasound; Mother’s washed (PLA1 neg) platelets; IVIG; Ultrasound;

SteroidsSteroids

Kasabach- MerrittKasabach- Merritt, TAR, TAR

Older child-ThrombocytopeniaOlder child-Thrombocytopenia

10 year old male treated with Valproic acid for seizures 10 year old male treated with Valproic acid for seizures presents with fever. He appears Ok with no skin lesions, presents with fever. He appears Ok with no skin lesions, lymphadenopathy or hepatosplenomegaly.lymphadenopathy or hepatosplenomegaly.

CBC WBC 5, Hb 12, Platelet 65,000. BUN 12, CBC WBC 5, Hb 12, Platelet 65,000. BUN 12, Creatinine 0.6 md/dl.Creatinine 0.6 md/dl.

What is the What is the MostMost likely cause: likely cause:– ITPITP (Immune thrombocytopenic purpura) (Immune thrombocytopenic purpura)– HUSHUS (Hemolytic Uremic Syndrome) (Hemolytic Uremic Syndrome)– HS PurpuraHS Purpura (Henoch- Schonlein Purpura) (Henoch- Schonlein Purpura)– ALLALL (Acute lymphoblastic leukemia) (Acute lymphoblastic leukemia)– Drug inducedDrug induced purpura purpura

Other causesOther causes

Hemolytic Uremic SyndromeHemolytic Uremic Syndrome– Hemolysis, sick patient, Uremia, microangiopathicHemolysis, sick patient, Uremia, microangiopathic

Henoch-Schonlein PurpuraHenoch-Schonlein Purpura– Purpuric lesions on lower extremities and buttocksPurpuric lesions on lower extremities and buttocks– Abd pain, arthritis. IgA depositionAbd pain, arthritis. IgA deposition

ALLALL– lymphadenopathy (LN), hepatosplenomegaly,other lymphadenopathy (LN), hepatosplenomegaly,other

cell lines affectedcell lines affected

Drug induced- Drug induced- – LikelyLikely– By reducing production or increasing destructionBy reducing production or increasing destruction

Petechiae, HSPPetechiae, HSP

ITPITP

Usually acute onset; immune mediated; post viralUsually acute onset; immune mediated; post viral

Peak 2-5 years of age, males=femalesPeak 2-5 years of age, males=females

Spontaneous bruises, petechiaeSpontaneous bruises, petechiae

PE –no lymphadenopathy (LN), hepatosplenomegaly.PE –no lymphadenopathy (LN), hepatosplenomegaly.

CBC- other cell lines normal, large plts on smearCBC- other cell lines normal, large plts on smear

Treat if plt< 10,000 or wet ITP, avoid NSAIDS, AspirinTreat if plt< 10,000 or wet ITP, avoid NSAIDS, Aspirin

Treat- Treat- IVIG best responseIVIG best response, 48-72 hours; Side effects., 48-72 hours; Side effects.

– Anti-D (WInRho) Rh+ ,hemolysis, quick responseAnti-D (WInRho) Rh+ ,hemolysis, quick response– Steroids good response, SE, inexpensive, need BMSteroids good response, SE, inexpensive, need BM

BM- Increased megakaryocytes, otherwise normalBM- Increased megakaryocytes, otherwise normal

Large plateletsLarge platelets

Normal platelet 7-10 daysNormal platelet 7-10 daysLarge platelets: Large platelets: – ITPITP– May Hegglin May Hegglin (Dohle (Dohle

bodies in neutrophils, Plt bodies in neutrophils, Plt function normal).function normal).

– Bernard Soulier Bernard Soulier syndrome (AR, Plat syndrome (AR, Plat function disorder).function disorder).

Small platelets: Small platelets: Wiskott Wiskott Aldrich syndromeAldrich syndrome ( X-linked, ( X-linked, recurrent infections,eczematoid recurrent infections,eczematoid rash, plt dysfunction)rash, plt dysfunction)

A 2 year old boy presents for evaluation of a chronic A 2 year old boy presents for evaluation of a chronic pruritic eruption. His medical history is remarkable for pruritic eruption. His medical history is remarkable for recurrent epistaxis, otitis media, and pneumonia. recurrent epistaxis, otitis media, and pneumonia. Physical examination reveals erythematous, slightly Physical examination reveals erythematous, slightly scaling patches on the trunk and in the antecubital and scaling patches on the trunk and in the antecubital and popliteal fossae. Petechiae are present profusely. Of popliteal fossae. Petechiae are present profusely. Of the following, these findings are MOST suggestive ofthe following, these findings are MOST suggestive of

1.1. Acrodermatitis enteropathicaAcrodermatitis enteropathica2.2. Ataxia telangiectasiaAtaxia telangiectasia3.3. Atopic dermatitisAtopic dermatitis4.4. Langerhans cell histiocytosisLangerhans cell histiocytosis5.5. Wiskott-Aldrich syndromeWiskott-Aldrich syndrome

Platelet function defectsPlatelet function defects

Normal platelet numberNormal platelet number

Glanzmann thrombastheniaGlanzmann thrombasthenia– AR, Abnormal aggregationAR, Abnormal aggregation– Bleeding disorder, check h/o consanguinityBleeding disorder, check h/o consanguinity

Hermansky Pudlak Syndrome:Hermansky Pudlak Syndrome:– AR, Decreased dense granules, In Puerto AR, Decreased dense granules, In Puerto

Ricans, Oculocutaneous albinismRicans, Oculocutaneous albinism

ThrombocytosisThrombocytosis

HH- - Hemorrhage, Hereditary Asplenia, Down Hemorrhage, Hereditary Asplenia, Down myeloprol.myeloprol.I- I- Infections, Kawasaki, Immune:Infections, Kawasaki, Immune:GVH, Nephrotic GVH, Nephrotic syndromesyndrome

P- P- Polycythemia vera, Myeloproliferative, EssentialPolycythemia vera, Myeloproliferative, EssentialL- L- Leukemia (CML) Leukemia (CML) A- A- Anemia,- Iron, Vit E, SideroblasticAnemia,- Iron, Vit E, SideroblasticT-T- TumorsTumorsE- E- Epinephrine, SteroidsEpinephrine, SteroidsL-L- Lymphoma, HodgkinsLymphoma, HodgkinsE- E- Exercise, T-Exercise, T- Trauma, FracturesTrauma, FracturesS-S- Splenectomy Splenectomy

AnemiaAnemia

An 18 month old girl brought in for pallor. Normal diet An 18 month old girl brought in for pallor. Normal diet and PMH. She is alert, interactive, only pallor, normal and PMH. She is alert, interactive, only pallor, normal vital signs, No hepatosplenomegaly, lymph nodes or vital signs, No hepatosplenomegaly, lymph nodes or bruises. bruises.

CBC- Normal WBC, Plt, Hb 4.5g/dl, MCV 74, CBC- Normal WBC, Plt, Hb 4.5g/dl, MCV 74,

AnemiaAnemia– Reduced productionReduced production– Increased destructionIncreased destruction– LossLoss

What else do you want??What else do you want??

Reticulocyte countReticulocyte count

Normal/Low- reduced productionNormal/Low- reduced production– Iron deficiency anemia- Iron deficiency anemia- MCV will be lowMCV will be low

– ALL (leukemia)- ALL (leukemia)- other findings, LN, HSMother findings, LN, HSM

– Diamond Blackfan anemia-Diamond Blackfan anemia- Us < 1 year of age; Us < 1 year of age; facial/thumb abn, Cong heart dis, MCV Incr, rbc ADA facial/thumb abn, Cong heart dis, MCV Incr, rbc ADA increased, responds to steroids, BMT curative.increased, responds to steroids, BMT curative.

– TECTEC: : Over 1 year of age, Pallor, transient rbc Over 1 year of age, Pallor, transient rbc production failure, improves, MCV and Hb F high production failure, improves, MCV and Hb F high during recovery, rbc transfusion, rbc ADA normal .during recovery, rbc transfusion, rbc ADA normal .

Normal smearNormal smear

Microcytic AnemiaMicrocytic Anemia

The diet of an 18-month-old child consists only of milk. She The diet of an 18-month-old child consists only of milk. She consumes 60 oz/day. Findings include: Comfortable, pallor, consumes 60 oz/day. Findings include: Comfortable, pallor, resting heart rate 85 beats/min, hemoglobin concentration 6.5 resting heart rate 85 beats/min, hemoglobin concentration 6.5 g/dL; mean corpuscular volume 57 fL; reticulocyte count 1.2%; g/dL; mean corpuscular volume 57 fL; reticulocyte count 1.2%; and guaiac-negative stool. Peripheral smear reveals marked and guaiac-negative stool. Peripheral smear reveals marked hypochromia and microcytosis.hypochromia and microcytosis.

Of the following, the most appropriate INITIAL step in the Of the following, the most appropriate INITIAL step in the management of this patient is tomanagement of this patient is to

A.A. administer intramuscular ironadminister intramuscular ironB.B. begin oral ferrous sulfatebegin oral ferrous sulfateC.C. obtain serum iron levelsobtain serum iron levelsD.D. refer for bone marrow evaluationrefer for bone marrow evaluationE.E. transfuse with packed red blood cellstransfuse with packed red blood cells

Microcytic anemiaMicrocytic anemia

Iron deficiencyIron deficiency

Low MCV, low MCHC, low retic, RDW will be normal Low MCV, low MCHC, low retic, RDW will be normal initially, will increase after treatment, Low Iron, Incr TIBC, initially, will increase after treatment, Low Iron, Incr TIBC, Transferrin low, Ferritin lowTransferrin low, Ferritin lowCauses: Inadequate dietary intakeCauses: Inadequate dietary intake– Toddlers, too much milk, less solids, Breast fed need Toddlers, too much milk, less solids, Breast fed need

iron supplementsiron supplements– poor absorptionpoor absorption– Blood loss: Menstrual, GI tract, Meckels, EpistaxisBlood loss: Menstrual, GI tract, Meckels, Epistaxis

D/D: D/D: Thalassemia trait- MCV much lower in prop to anemia,Thalassemia trait- MCV much lower in prop to anemia,Anemia of chronic disease- low Fe, low TIBC, Anemia of chronic disease- low Fe, low TIBC, normal/high Ferritin.normal/high Ferritin.

Thalassemia MinorThalassemia Minor

Quantitative defect in Quantitative defect in globin chainsglobin chains– Reduced production of Reduced production of

Beta chainsBeta chains

Hb electrophoresisHb electrophoresis– Hb A- 2 Alpha, 2 BetaHb A- 2 Alpha, 2 Beta– Hb F- 2 Alpha, 2 GammaHb F- 2 Alpha, 2 Gamma– Hb A2- 2 Alpha, 2 DeltaHb A2- 2 Alpha, 2 Delta

Excess Alpha combines Excess Alpha combines with Gamma, Delta- with Gamma, Delta- Increased Hb F and A 2.Increased Hb F and A 2.Smear abnormalities Smear abnormalities significant even with significant even with MILDMILD anemia. anemia.

AnemiaAnemiaLow MCV, normal RDW, Low MCV, normal RDW, normal reticnormal reticSmear shows Smear shows anisopoikulocytosis, anisopoikulocytosis, target cells, microcytes, target cells, microcytes, misshapen cells, misshapen cells, basophilic stipplingbasophilic stipplingHb Electrophoresis: Hb Electrophoresis: Increased Hb A2 and/or Increased Hb A2 and/or F.F.Normal iron studies, no Normal iron studies, no response to ironresponse to iron

Thalassemia MajorThalassemia Major

No production of Beta chainsNo production of Beta chainsAutosomal recessiveAutosomal recessive25 % chance with each pregnancy25 % chance with each pregnancyPre natal testing for carriersPre natal testing for carriersChorionic villous sampling for diagnosisChorionic villous sampling for diagnosisTransfusion dependent-allows for normal developmentTransfusion dependent-allows for normal developmentPen Prophylaxis, Anti oxidantsPen Prophylaxis, Anti oxidantsSplenectomy after age 5Splenectomy after age 5Iron overload- inherent and transfusionIron overload- inherent and transfusionNeed chelatorsNeed chelators

Thalassemia- AlphaThalassemia- Alpha

Reduced Alpha chainsReduced Alpha chains

4 types- carried on 4 allelles. (4 types- carried on 4 allelles. (x x/x xx x/x x))

One absent- Silent carrier (One absent- Silent carrier (x-/x x)x-/x x)

2 absent- Alpha Thal trait (2 absent- Alpha Thal trait (xx/- - or x -/x -xx/- - or x -/x -))

3 absent- Hb H disease (3 absent- Hb H disease (x -/- -x -/- - ) Has 4 excess ) Has 4 excess Beta chains)Beta chains)

4 absent- Hydrops fetalis (- -/- -)4 absent- Hydrops fetalis (- -/- -)

NB period: Excess Gamma forms Hb Barts- NB period: Excess Gamma forms Hb Barts- FAST moving Hb on Newborn screeningFAST moving Hb on Newborn screening

CaseCase

3 year old patient is brought to the ER with 3 year old patient is brought to the ER with complaints of feeling very tired over the complaints of feeling very tired over the past 3 days.past 3 days.

Patient is pale, jaundiced with the spleen Patient is pale, jaundiced with the spleen tip palpable.tip palpable.

CBC Hb 5, Retic 5 %, LDH Increased,CBC Hb 5, Retic 5 %, LDH Increased,

What does this sound like??What does this sound like??

Reticulocyte count- IncreasedReticulocyte count- Increased

HemolysisHemolysis– Intrinsic-Intrinsic-

Membrane defects-Hereditary spherocytosis (HS)Membrane defects-Hereditary spherocytosis (HS)

Enzyme-G 6 PD deficiencyEnzyme-G 6 PD deficiency

HemoglobinopathiesHemoglobinopathies

– Extrinsic- Extrinsic- AIHA (Auto-immune hemolytic anemia), AIHA (Auto-immune hemolytic anemia), DIC, IV hemolysisDIC, IV hemolysis

LossLoss– Blood lossBlood loss

Hemolytic anemiaHemolytic anemia

History; Recent infection, drug exposure, History; Recent infection, drug exposure, illness, dark urine, anorexia, fatigue, pallorillness, dark urine, anorexia, fatigue, pallor

Family h/o gallstones, splenectomyFamily h/o gallstones, splenectomy

Physical Examination: Pallor, Tachycardia, Physical Examination: Pallor, Tachycardia, Tachypnea, Splenomegaly.Tachypnea, Splenomegaly.

Peripheral smear: Blisters, spherocytesPeripheral smear: Blisters, spherocytes

G-6PD deficiencyG-6PD deficiency

A previously normal African-A previously normal African-American child visited Africa and American child visited Africa and was given malarial prophylaxis. was given malarial prophylaxis. He experienced pallor, fatigue, He experienced pallor, fatigue, and dark urine. His hemoglobin and dark urine. His hemoglobin level decreased from 14.8 to 9 level decreased from 14.8 to 9 g/dL. The most likely diagnosis g/dL. The most likely diagnosis isis– Hereditary spherocytosisHereditary spherocytosis– Sickle cell diseaseSickle cell disease– HepatitisHepatitis– G6PD deficiencyG6PD deficiency

Avoid certain medications Avoid certain medications (Sulfas), Fava beans in (Sulfas), Fava beans in Mediterranean.Mediterranean.

Seen in African American- avoid Seen in African American- avoid moth balls.moth balls.

Blister cellsBlister cells

Bite cellsBite cells

Blister cellsBlister cells

Bite cellsBite cells

SpherocytesSpherocytes

SpherocytesSpherocytes

Nucleated rbcNucleated rbc

Coombs-AIHACoombs-AIHA

Osmotic fragility-HSOsmotic fragility-HS

HS- with severe anemiaHS- with severe anemiaAll patients with hemolytic anemia are susceptibleAll patients with hemolytic anemia are susceptible

A 6 year old girl who has hereditary spherocytosis A 6 year old girl who has hereditary spherocytosis presents with a 1 week history of fever. Physical presents with a 1 week history of fever. Physical examination and history reveal abdominal pain, examination and history reveal abdominal pain, vomiting, fatigue and pallor. Her hemoglobin is vomiting, fatigue and pallor. Her hemoglobin is typically about 10 g/dL with a reticulocyte count of 9%, typically about 10 g/dL with a reticulocyte count of 9%, but now, her hemoglobin is 4 g/dL and the reticulocyte but now, her hemoglobin is 4 g/dL and the reticulocyte count is 1%. Her bilirubin is 1 mg/dL. Of the following, count is 1%. Her bilirubin is 1 mg/dL. Of the following, the MOST likely cause for this girl’s present illness is the MOST likely cause for this girl’s present illness is infection withinfection with

– Coxsackie virusCoxsackie virus– Epstein-Barr virusEpstein-Barr virus– Hepatitis A virusHepatitis A virus– Influenza A virusInfluenza A virus– Parvovirus B19Parvovirus B19

Newborn ScreeningNewborn Screening

You get a call from a frantic parent because she You get a call from a frantic parent because she received a letter from the State regarding her received a letter from the State regarding her baby’s test results on NBS.baby’s test results on NBS.FS- FS- SSSS disease, disease, S-BS-B00 Thal, Sickle cell w/ HPFH. Thal, Sickle cell w/ HPFH.FSA- FSA- Sickle BSickle B+ + thalthal, Sickle cell trait, Sickle cell traitFSC- FSC- SC diseaseSC diseaseFAS- Sickle cell traitFAS- Sickle cell traitFAC- Hb C traitFAC- Hb C traitFAE- Hb E traitFAE- Hb E traitFEFE - Hb EE disease, E-Thal- Hb EE disease, E-Thal

Sickle cellSickle cell

Hemolysis- life span 20-50 Hemolysis- life span 20-50 days. Abnormal cell shape, days. Abnormal cell shape, abnormal adherence to abnormal adherence to endothelium, decreased endothelium, decreased oxygenation, Increased oxygenation, Increased polymerization.polymerization.Symptoms start by 2-4 months Symptoms start by 2-4 months of age.of age.Hb electrophoresis, S >75 %.Hb electrophoresis, S >75 %.Start Penicillin daily and give Start Penicillin daily and give until age 5. Prevention of until age 5. Prevention of pneumococcal infections.pneumococcal infections.PPV (Pnu-23) age 2, 5PPV (Pnu-23) age 2, 5Folic acid dailyFolic acid daily

Sickle cell- Higher riskSickle cell- Higher risk

High WBCHigh WBC

Low HemoglobinLow Hemoglobin

Multiple episodes of dactylitisMultiple episodes of dactylitis

Low Hb FLow Hb F

Associated Alpha thal trait- better clinical Associated Alpha thal trait- better clinical coursecourse

Sickle cell crisesSickle cell crises

Vaso-occlusive crisis-Vaso-occlusive crisis-dactylitis, long bones, dactylitis, long bones, back, chest. Trt. Pain back, chest. Trt. Pain meds, hydration.meds, hydration.

Aplastic crisis: low Hb, Aplastic crisis: low Hb, low retic, Sec to low retic, Sec to Parvovirus infection.Parvovirus infection.

Splenic sequestration Splenic sequestration crisis: spleen palpationcrisis: spleen palpation

Hyperhemolytic crisisHyperhemolytic crisis

CaseCase

12 year old female with SS disease 12 year old female with SS disease complains of right sided chest pain and complains of right sided chest pain and upper back pain for one day.upper back pain for one day.

P/E reveals slightly reduced breath P/E reveals slightly reduced breath sounds and a Pulse OX of 86 %. CXR sounds and a Pulse OX of 86 %. CXR shows an infiltrate on the right lower lobe.shows an infiltrate on the right lower lobe.

What is your diagnosis?What is your diagnosis?

What will you do next?What will you do next?

Sickle cell Sickle cell Acute Chest SyndromeAcute Chest Syndrome

New infiltrate on X-ray, fever, chest pain, New infiltrate on X-ray, fever, chest pain, back pain, hypoxia.back pain, hypoxia.Due to infarction, infection, BM fat Due to infarction, infection, BM fat embolismembolismTreat: Antibiotics to cover pneumococcus, Treat: Antibiotics to cover pneumococcus, Mycoplasma, Chlamydia, Bronchodilator, Mycoplasma, Chlamydia, Bronchodilator, Oxygen, Incentive spirometry, transfusion, Oxygen, Incentive spirometry, transfusion, Steroids (controversial).Steroids (controversial).Avoid overhydrationAvoid overhydration

Pulmonary HypertensionPulmonary Hypertension

Prevalence of pulmonary HT in SCD from 20-40 %.The presence of hemolysis, chronic anemia, and the need for frequent transfusions were directly associated with development of PHT.On follow-up, PHT was significantly associated with an increased risk of death. -Am J Hematol July 2004

-N Engl J Med Feb 2004.

TCD- Transcranial DopplerTCD- Transcranial Doppler

A routine TCD on a 4 A routine TCD on a 4 year old patient with year old patient with SS disease shows a SS disease shows a Cerebral blood flow Cerebral blood flow (CBF) of 210 (CBF) of 210 cm/second.cm/second.What is the next What is the next step?step?STOP studies- STOP STOP studies- STOP I and III and II

Sickle cell and StrokeSickle cell and Stroke

Affects 10 % of patientsAffects 10 % of patientsInfarctive stroke (younger patients) and Infarctive stroke (younger patients) and Hemorrhagic stroke (older)Hemorrhagic stroke (older)STOP I study established the role of yearly TCD STOP I study established the role of yearly TCD (transcranial doppler) to measure cerebral blood (transcranial doppler) to measure cerebral blood flow velocity as a tool for determining stroke risk.flow velocity as a tool for determining stroke risk.Transfusion therapy as current therapy for Transfusion therapy as current therapy for high risk patients (CBF> 200cm/sec)high risk patients (CBF> 200cm/sec)Reversal of CBF velocity is not sufficient to stop Reversal of CBF velocity is not sufficient to stop transfusion therapy. (STOP II)transfusion therapy. (STOP II)

Sickle cell and TransfusionsSickle cell and Transfusions

Transfusion indications:Transfusion indications:– Acute anemia (Aplastic, Hyperhemolytic, Sequestration)Acute anemia (Aplastic, Hyperhemolytic, Sequestration)– Hypoxia (ACS, chronic lung disease, Pulmonary hypertension)Hypoxia (ACS, chronic lung disease, Pulmonary hypertension)– Stroke and stroke preventionStroke and stroke prevention– Intractable pain, pre-operativeIntractable pain, pre-operative

Types of transfusionsTypes of transfusions– IntermittentIntermittent– Chronic simpleChronic simple– Exchange (Partial, Total, Erythrocytapheresis)Exchange (Partial, Total, Erythrocytapheresis)– Hypertransfusion (transfusions in an effort to prevent patient Hypertransfusion (transfusions in an effort to prevent patient

from producing their own red cells)from producing their own red cells)

Iron overloadIron overload

One unit -200mg IronOne unit -200mg IronNo physiologic way of No physiologic way of removalremoval 10-20 transfusions10-20 transfusionsDesferioxamine available. Desferioxamine available. Can be given IV or subq Can be given IV or subq infusion or subq shots.infusion or subq shots.Compliance an issue.Compliance an issue.December 2005- Oral December 2005- Oral chelator available chelator available (Deferasirox)- FDA (Deferasirox)- FDA approved.approved.

Sickle cell and HydoxyureaSickle cell and Hydoxyurea

FDA approved for adultsFDA approved for adultsStudies in children demonstrated efficacy Studies in children demonstrated efficacy and safety.and safety.Increases hemoglobin F levelIncreases hemoglobin F levelIncreases hemoglobinIncreases hemoglobinDecreases WBC – ancillary effectDecreases WBC – ancillary effectHydroxyurea is recommended by the Hydroxyurea is recommended by the hematologist for patients who have recurrent hematologist for patients who have recurrent vaso-occlusive crises, Acute chest syndrome. vaso-occlusive crises, Acute chest syndrome.

Other important pointsOther important points

Median life expectancy:Median life expectancy:– Males 42 years, females 48 yearsMales 42 years, females 48 years

Improvement related to Penicillin, Improvement related to Penicillin, immunizations, education.immunizations, education.

Bone marrow transplant (BMT) is a cureBone marrow transplant (BMT) is a cure

Cord blood storageCord blood storage

CaseCase

A healthy 5 year old boy has a 2 day hx of A healthy 5 year old boy has a 2 day hx of fever, P/E normal, No hepatosplenomegaly, fever, P/E normal, No hepatosplenomegaly, LN, no focus of infection. CBC WBC 3, LN, no focus of infection. CBC WBC 3, Neutrophils 25 %, Hb 12, Platelet 200X10Neutrophils 25 %, Hb 12, Platelet 200X1099/L, /L, ANC 750.ANC 750.

The most appropriate management would be:The most appropriate management would be:1.1. Amoxicillin for 10 daysAmoxicillin for 10 days2.2. G- CSF for 10 days.G- CSF for 10 days.3.3. BM aspirateBM aspirate4.4. Refer to a hematologistRefer to a hematologist5.5. Repeat CBC in 1-2 weeksRepeat CBC in 1-2 weeks

NeutropeniaNeutropenia

Severe neutropenia ANC < 500/mm3 Severe neutropenia ANC < 500/mm3 Viral infection(hepatitis, Influenza, Measles, Viral infection(hepatitis, Influenza, Measles, Rubella, RSV, EBV)- No Rx.Rubella, RSV, EBV)- No Rx.Cyclic neutropeniaCyclic neutropenia– Sporadic Autosomal dominant disorderSporadic Autosomal dominant disorder– 21 day intervals, nadir < 200/uL21 day intervals, nadir < 200/uL– G CSF treatmentG CSF treatment

Severe Congenital Neutropenia (Kostmann)Severe Congenital Neutropenia (Kostmann)– AR, ANC< 200, BM arrest, high dose G CSF, risk of AR, ANC< 200, BM arrest, high dose G CSF, risk of

malignancy (MDS/AML) and sepsis. BMT cure.malignancy (MDS/AML) and sepsis. BMT cure.

NeutropeniaNeutropenia

AutoImmune neutropeniaAutoImmune neutropenia– Self limited, G CSF only if necessarySelf limited, G CSF only if necessary– Mild infectionsMild infections

Schwachman-Diamond SyndromeSchwachman-Diamond Syndrome– AR, Exocrine pancreatic failure, short stature, AR, Exocrine pancreatic failure, short stature,

recurrent infections, mataphyseal dysostoses.recurrent infections, mataphyseal dysostoses.– G-CSF, Risk of myelodysplasia and AML, BMT G-CSF, Risk of myelodysplasia and AML, BMT

curativecurative

Chronic benign NeutropeniaChronic benign Neutropenia– ??AI, < 3 years of age, skin and mucous membrane ??AI, < 3 years of age, skin and mucous membrane

infections, Antibodiesinfections, Antibodies

CaseCase

A 2-year-old boy has had several 10-day-long episodes of fever, A 2-year-old boy has had several 10-day-long episodes of fever, mouth ulcerations, stomatitis, and pharyngitis. These episodes have mouth ulcerations, stomatitis, and pharyngitis. These episodes have occurred at about monthly intervals. Absolute neutrophil counts occurred at about monthly intervals. Absolute neutrophil counts have been 50/mm³on day 1 of each illness, 500/mm³ on day 10, and have been 50/mm³on day 1 of each illness, 500/mm³ on day 10, and 1,500/mm³ on day 14.1,500/mm³ on day 14.

Among the following, the MOST likely cause for the findings in this Among the following, the MOST likely cause for the findings in this patient ispatient is

A. chronic benign neutropeniaA. chronic benign neutropeniaB. cyclic neutropeniaB. cyclic neutropeniaC. Schwachman-Diamond syndromeC. Schwachman-Diamond syndromeD. severe congenital neutropeniaD. severe congenital neutropeniaE.. transient viral bone marrow suppressionE.. transient viral bone marrow suppression

Approach to a bleeding patientApproach to a bleeding patient

History:History:– h/o trauma, H/o similar episodesh/o trauma, H/o similar episodes– h/o bruising, h/o surgery in the pasth/o bruising, h/o surgery in the past– h/o circumcision, bleeding from the umbilical h/o circumcision, bleeding from the umbilical

stump ,delayed wound healingstump ,delayed wound healing– Time of onset (Acute/chronic), any challenges Time of onset (Acute/chronic), any challenges

eg. trauma, surgery or menstruationeg. trauma, surgery or menstruation– Overall health ( well/sick); Evidence of shock.Overall health ( well/sick); Evidence of shock.– bleeding disorders in the family (maternal bleeding disorders in the family (maternal

uncles and aunts, grandparents)uncles and aunts, grandparents)

Abnormal BleedingAbnormal Bleeding

Epistaxis unrelieved by 15 minutes of Epistaxis unrelieved by 15 minutes of pressure, both nostrils, requiring an ER pressure, both nostrils, requiring an ER visit, documented drop of Hb. visit, documented drop of Hb. Menstrual periods( amount, pads, Menstrual periods( amount, pads, duration)duration) Bleeding after procedures (circumcision, Bleeding after procedures (circumcision, dental extractions, T and A-dental extractions, T and A-delayed bleeddelayed bleed))Ecchymoses/bruising inconsistent with Ecchymoses/bruising inconsistent with the degree of traumathe degree of trauma

CaseCase

13 year old girl just started her periods and 13 year old girl just started her periods and has been bleeding for the past 16 days. has been bleeding for the past 16 days. She has used 14 pads a day and is tired. She has used 14 pads a day and is tired. Her vital signs were stable, Hb was 9.5, Her vital signs were stable, Hb was 9.5, PT, PTT were normal. The mother had PT, PTT were normal. The mother had heavy periods and her 6 year old brother heavy periods and her 6 year old brother has nose bleeds for the past 2 years.has nose bleeds for the past 2 years.

Bleeding patientBleeding patient

Physical Examination:Physical Examination:Type of bleeding: Superficial or deepType of bleeding: Superficial or deep– Bruises, PetechiaeBruises, Petechiae– Epistaxis, Gum bleeding, Excessive menstrual Epistaxis, Gum bleeding, Excessive menstrual

bleedingbleeding– Site of bleedingSite of bleeding– Bleeding into the joints and soft tissuesBleeding into the joints and soft tissues– Look for evidence of shockLook for evidence of shock– Medication history (Aspirin, NSAIDS) Medication history (Aspirin, NSAIDS)

Coagulation cascadeCoagulation cascade

Lab studiesLab studies(What do they measure?)(What do they measure?)

CBC and Peripheral smearCBC and Peripheral smear

PT, INR and PTTPT, INR and PTT– PT - Factor VII, common pathwayPT - Factor VII, common pathway– PTT- Factor VIII, IX, XI, common pathwayPTT- Factor VIII, IX, XI, common pathway

Mixing studies (Inhibitors and deficiency)Mixing studies (Inhibitors and deficiency)

Specific coagulation factor assaysSpecific coagulation factor assays

Fibrinogen Fibrinogen

Circulating anticoagulantCirculating anticoagulant

Mixing studyMixing study

If PT or PTT is prolonged, ask for a mixing If PT or PTT is prolonged, ask for a mixing study.study.

Mix patient plasma with equal amount of normal Mix patient plasma with equal amount of normal plasma, the test will normalize if the abnormal plasma, the test will normalize if the abnormal result is because of a deficiency in factor. result is because of a deficiency in factor.

If there is an anticoagulant, it will not normalize If there is an anticoagulant, it will not normalize or even if it does, it will become abnormal again or even if it does, it will become abnormal again after incubation.after incubation.

Factor XIII and VII deficiencyFactor XIII and VII deficiency

Factor XIIIFactor XIIIRare Autosomal Rare Autosomal RecessiveRecessiveIf all tests are normal:If all tests are normal:– PT, PTT, Platelet count PT, PTT, Platelet count

and function, VW tests all and function, VW tests all normal.normal.

– Think of doing Factor XIII Think of doing Factor XIII assay for deficiencyassay for deficiency

Bleeding after umbilical Bleeding after umbilical stump separationstump separationAbnormal clot solubility in Abnormal clot solubility in 5M Urea5M Urea

Factor VIIFactor VIIIntracranial hemorrhageIntracranial hemorrhageRare, homozygous stateRare, homozygous stateProlonged PT, n PTTProlonged PT, n PTTTreatment with Treatment with Recombinant F VIIRecombinant F VII

CaseCase

A A healthy 2-day-old boy born at term undergoes circumcision healthy 2-day-old boy born at term undergoes circumcision prior to discharge from the hospital. Bleeding was noted at the prior to discharge from the hospital. Bleeding was noted at the site of circumcision 10 hours after the procedure and has site of circumcision 10 hours after the procedure and has increased steadily over the past 4 hours. Findings on physical increased steadily over the past 4 hours. Findings on physical examination are unremarkable except for bleeding along 2 to 3 examination are unremarkable except for bleeding along 2 to 3 mm of the surgical site; there are no petechiae or purpura.mm of the surgical site; there are no petechiae or purpura.

Of the following, the MOST likely cause of the bleeding isOf the following, the MOST likely cause of the bleeding is

A.A. disseminated intravascular coagulationdisseminated intravascular coagulationB.B. factor VIII deficiency hemophiliafactor VIII deficiency hemophiliaC.C. immune thrombocytopenic purpuraimmune thrombocytopenic purpuraD.D. neonatal alloimmune thrombocytopenianeonatal alloimmune thrombocytopeniaE.E. von Willebrand diseasevon Willebrand disease

Bleeding disordersBleeding disorders

Tests for bleedingTests for bleeding

Hemophilia AHemophilia A

Hemophilia BHemophilia B

Hemophilia CHemophilia C

VW DiseaseVW Disease

Hemophilia Hemophilia

Factor VIII deficiency (Hemophilia A)-85%Factor VIII deficiency (Hemophilia A)-85%– X-linked recessive, Carriers asymptomaticX-linked recessive, Carriers asymptomatic– Severe<1%, Moderate 1-5, Mild 6-30 %Severe<1%, Moderate 1-5, Mild 6-30 %– Treat Recombinant Factor VIII1 unit/kg raises factor Treat Recombinant Factor VIII1 unit/kg raises factor

level by 2 %. Half life 12 hrs. DDAVP for mild cases.level by 2 %. Half life 12 hrs. DDAVP for mild cases.– Joint bleeds need100%, muscle bleeds 50 %.Joint bleeds need100%, muscle bleeds 50 %.– 30 % develop inhibitors after infusions with 30 % develop inhibitors after infusions with

concentrate (Approx 50 infusions)concentrate (Approx 50 infusions)

Factor IX deficiency (Hemophilia B)Factor IX deficiency (Hemophilia B)– X-linked recessive, less commonX-linked recessive, less common

HemophiliaHemophilia

A patient with Hemophilia A has asked you A patient with Hemophilia A has asked you about the possibility of his children being about the possibility of his children being affected by the disease. The partner is normal.affected by the disease. The partner is normal.

a. There is a 50 % chance that his sons a. There is a 50 % chance that his sons will have the disease.will have the disease.

b. There is a 50 % chance that his b. There is a 50 % chance that his daughters will be carriersdaughters will be carriers

c. There is a 100 % chance that his sons c. There is a 100 % chance that his sons will have the diseasewill have the disease

d. There is a 100 % chance that his d. There is a 100 % chance that his daughters will be carriersdaughters will be carriers

Answer was dAnswer was dCaseCase

13 year old girl just started her periods and 13 year old girl just started her periods and has been bleeding for the past 16 days. has been bleeding for the past 16 days. She has used 14 pads a day and is tired. She has used 14 pads a day and is tired. Her vital signs are stable, Her vital signs are stable, Hb 9.5, PT, PTT normal. Hb 9.5, PT, PTT normal. The mother had heavy periods and her 6 The mother had heavy periods and her 6 year old brother has nose bleeds for the year old brother has nose bleeds for the past 2 years.past 2 years.Likely to have:Likely to have:

Von Willebrand’s DiseaseVon Willebrand’s Disease1-2 % of population1-2 % of population

Type I - Type I - 80 % of cases;80 % of cases; Quantitative defect, Autosomal Quantitative defect, Autosomal dominant (AD)dominant (AD)Type 2 - 15-20 %, Qualitative defectType 2 - 15-20 %, Qualitative defect– 2A, 2b (thrombocytopenia), 2M, 2A, 2b (thrombocytopenia), 2M, – 2N (AR)2N (AR)

Type 3 - Type 3 - Severe (similar to hemophilia A)Severe (similar to hemophilia A)Autosomal recessive (AR)Autosomal recessive (AR)DDAVP- DDAVP- Releases VWF from endothelial cells and stabilizes Releases VWF from endothelial cells and stabilizes Factor VIIIFactor VIII– SE: Water retention, Tachyphylaxis, hyponatremia. SE: Water retention, Tachyphylaxis, hyponatremia. – For mild Hemophilia, Type I VWD, 2For mild Hemophilia, Type I VWD, 2– Contra-indicated in Type 2BContra-indicated in Type 2B

Plasma derived VWF containing concentratesPlasma derived VWF containing concentrates

Thrombophilia- CaseThrombophilia- Case

A 14 year old male presents with chest pain and difficulty A 14 year old male presents with chest pain and difficulty breathing. He notes that his right calf has been swollen breathing. He notes that his right calf has been swollen for the last 3 days and he has difficulty placing his foot for the last 3 days and he has difficulty placing his foot on the ground. P/E Pain on dorsiflexion, Air entry on the ground. P/E Pain on dorsiflexion, Air entry reduced. CXR and EKG are normal. VQ scan shows a reduced. CXR and EKG are normal. VQ scan shows a filling defect and a diagnosis of DVT and pulmonary filling defect and a diagnosis of DVT and pulmonary embolism is made.embolism is made.What are the important questions on history?What are the important questions on history?– History of DVT in family membersHistory of DVT in family members– H/o recurrent late miscarriages in mother and her sisters.H/o recurrent late miscarriages in mother and her sisters.– H/o trauma and precipitating factorsH/o trauma and precipitating factors

CausesCauses

Factor V Leiden (Activated Protein C resistance)Factor V Leiden (Activated Protein C resistance)

Prothrombin G 20210A gene mutation Prothrombin G 20210A gene mutation

Protein C deficiency and activityProtein C deficiency and activity

Protein S deficiency and activity.Protein S deficiency and activity.

Anti thrombin III deficiency and activity.Anti thrombin III deficiency and activity.

HyperhomocystenemiaHyperhomocystenemia

Antiphospholipid syndromeAntiphospholipid syndrome

Rare disorders-DysfibrinogenemiaRare disorders-Dysfibrinogenemia

Hypercoagulable statesHypercoagulable states

Factor V Leiden- Factor V Leiden- 40-50 % cases40-50 % cases– Abnormal factor V cannot be cleaved and inactivated Abnormal factor V cannot be cleaved and inactivated

by Protein C & there is thrombosis.by Protein C & there is thrombosis.– Common in Caucasians (5.3 %)Common in Caucasians (5.3 %)– Non-O blood group more prone to thrombosisNon-O blood group more prone to thrombosis– Homozygotes 1%Homozygotes 1%

Protein C- Vit K dependent, produced in liverProtein C- Vit K dependent, produced in liver– Activated PC inactivates coagulation factors Va and Activated PC inactivates coagulation factors Va and

VIIIa, The inhibitory effect is enhanced by VIIIa, The inhibitory effect is enhanced by Protein S.Protein S.– Venous thromboembolism, Neonatal purpura Venous thromboembolism, Neonatal purpura

fulminans, Warfarin-induced skin necrosis.fulminans, Warfarin-induced skin necrosis.

Hypercoagulable statesHypercoagulable states

G20210A Prothrombin mutationG20210A Prothrombin mutation– Increase in the prothrombin, a precursor of thrombinIncrease in the prothrombin, a precursor of thrombin– Vitamin K-dependent protein which is synthesized in Vitamin K-dependent protein which is synthesized in

the liverthe liver– Heterozygous carriers have an increased risk of deep Heterozygous carriers have an increased risk of deep

vein and cerebral vein thrombosis. vein and cerebral vein thrombosis.

Antithrombin (AT, formerly called AT III)Antithrombin (AT, formerly called AT III)– vitamin K-independent glycoprotein that is a major vitamin K-independent glycoprotein that is a major

inhibitor of thrombin and factors Xa and IXa. inhibitor of thrombin and factors Xa and IXa. – In the presence of heparin, thrombin or factor Xa is In the presence of heparin, thrombin or factor Xa is

rapidly inactivated by AT; this is referred to as the rapidly inactivated by AT; this is referred to as the heparin cofactor activityheparin cofactor activity of AT. of AT.

TransfusionTransfusion

A 4-year-old boy develops massive bleeding following a A 4-year-old boy develops massive bleeding following a tonsillectomy. A transfusion is indicated, but his parents are tonsillectomy. A transfusion is indicated, but his parents are extremely concerned about the risk of a transfusion-mediated extremely concerned about the risk of a transfusion-mediated infection. They want to know what tests are performed on donated infection. They want to know what tests are performed on donated units of blood before they consent to the procedure.units of blood before they consent to the procedure.Of the following, your discussion is MOST likely to include the Of the following, your discussion is MOST likely to include the statement thatstatement that

A. all units are tested only for hepatitis B and CA. all units are tested only for hepatitis B and CB. all units are tested only for human immuno-deficiency virus (HIV)B. all units are tested only for human immuno-deficiency virus (HIV)C. all units are tested for HIV, hepatitis B, and hepatitis CC. all units are tested for HIV, hepatitis B, and hepatitis CD. all units are tested for HIV, hepatitis B, hepatitis C, sickle cell trait, D. all units are tested for HIV, hepatitis B, hepatitis C, sickle cell trait,

cytomegalovirus, and Epstein-Barr viruscytomegalovirus, and Epstein-Barr virusE. only units obtained from donors who have one or more risk factors E. only units obtained from donors who have one or more risk factors

are screened for HIVare screened for HIV

Transfusion- NotesTransfusion- Notes

CMV negative- give leukocyte reduced.CMV negative- give leukocyte reduced.

Irradiated products- To prevent GVHDIrradiated products- To prevent GVHD

Washed cellsWashed cells

Phenotype matchedPhenotype matched– To prevent allo-immunizationTo prevent allo-immunization

Sickle negativeSickle negative

CANCER IN CHILDRENCANCER IN CHILDREN

Distribution-All agesDistribution-All agesChildhood Cancer Distribution Leukemia

Lymphoma

Brain Tumor

Soft tissue sarcoma

Germ call

Bone

Neuroblastoma

Renal

Retino

Hepato

Carcinoma

Other

Cancer in ChildrenCancer in Children

Leukemias, Brain Leukemias, Brain tumors, Lymphomastumors, Lymphomas

22ndnd leading cause of leading cause of death 1-14yrsdeath 1-14yrs

12,400 cases per 12,400 cases per yearyear

Proto-Oncogenes imp Proto-Oncogenes imp for function-Activatedfor function-Activated

-Amplification --n-myc-Amplification --n-myc

-Point mutation-NRA’s-Point mutation-NRA’s

-Translocation- Ph -Translocation- Ph chromosome t (9:22); chromosome t (9:22); BCR-ABLBCR-ABL

CaseCase

18 month old comes to the clinic with 18 month old comes to the clinic with complaints of pallor. No fever, appetite complaints of pallor. No fever, appetite change, wt loss. P/E Pale, HR 110/min, No change, wt loss. P/E Pale, HR 110/min, No HSM, bruise left buttock, arms and abdomen.HSM, bruise left buttock, arms and abdomen.

MOSTMOST likely diagnosis likely diagnosis1.1. ALLALL2.2. Child abuseChild abuse3.3. ITPITP4.4. Iron deficiency anemiaIron deficiency anemia5.5. TEC (Transient erythroblastopenia of TEC (Transient erythroblastopenia of

childhood)childhood)

ALLALL (Acute Lymphoblastic leukemia) (Acute Lymphoblastic leukemia)

This suggests 2 cell lines are affected. This suggests 2 cell lines are affected. Consider ALL, viral infections, aplastic Consider ALL, viral infections, aplastic anemia, myelofibrosis, neuroblastoma.anemia, myelofibrosis, neuroblastoma.

Child abuse: unlikely to have pallor unless Child abuse: unlikely to have pallor unless massive traumamassive trauma

ITP: can have mild anemia, but here, the ITP: can have mild anemia, but here, the HR suggests significant anemiaHR suggests significant anemia

Iron def and TEC: No bruisingIron def and TEC: No bruising

A 6-year-old girl has had diffuse aching in her arms, legs, and back A 6-year-old girl has had diffuse aching in her arms, legs, and back for more than 2 weeks. Results of laboratory tests include for more than 2 weeks. Results of laboratory tests include hemoglobin, 9.4 g/dL; white blood cell count, 5,600/mm³ with no hemoglobin, 9.4 g/dL; white blood cell count, 5,600/mm³ with no abnormal cells noted on smear; and platelet count, 106,000/mm³. abnormal cells noted on smear; and platelet count, 106,000/mm³. Radiographs of long bones reveal osteolytic lesions and radiolucent Radiographs of long bones reveal osteolytic lesions and radiolucent metaphyseal growth arrest lines.metaphyseal growth arrest lines.

Of the following, the MOST likely cause of these findings isOf the following, the MOST likely cause of these findings is

A.A. acute lymphoblastic leukemiaacute lymphoblastic leukemiaB.B. aplastic anemiaaplastic anemiaC.C. Gaucher diseaseGaucher diseaseD.D. lead poisoninglead poisoningE.E. multifocal osteomyelitismultifocal osteomyelitis

ALL ALL (Acute Lymphoblastic leukemia)(Acute Lymphoblastic leukemia)

Can present with Can present with generalized bone paingeneralized bone pain

Bruising, nose bleedsBruising, nose bleeds

Unusual fevers, Unusual fevers, infectioninfection

Lymphadenopathy, Lymphadenopathy, hepatosplenomegalyhepatosplenomegaly

ALLALL (Acute Lymphoblastic leukemia) (Acute Lymphoblastic leukemia)Abnormal to see blasts in the peripheral smearAbnormal to see blasts in the peripheral smear

Diagnosis: >25 % blasts in the BM.Diagnosis: >25 % blasts in the BM.

Normal marrow has 5 % blastsNormal marrow has 5 % blasts

Single most common childhood cancer (29% of Single most common childhood cancer (29% of all childhood cancers); 2500-3500 cases per all childhood cancers); 2500-3500 cases per yearyear

Peak age 2-5 yearsPeak age 2-5 years

More likely in Trisomy 21, Ataxia-Telangiectasia, More likely in Trisomy 21, Ataxia-Telangiectasia, Bloom syndrome, Fanconi anemia.Bloom syndrome, Fanconi anemia.

ALL TreatmentALL Treatment

Induction:Induction: 4-6 weeks, 95 % remission; 4-6 weeks, 95 % remission; Vincristine, Corticosteroids, L-Asparaginase and Vincristine, Corticosteroids, L-Asparaginase and AnthracyclineAnthracyclineConsolidation /delayed IntensificationConsolidation /delayed Intensification:: 6-12 months; rotating drugs.6-12 months; rotating drugs.MaintenanceMaintenance : Daily oral 6-MP, weekly MTX, : Daily oral 6-MP, weekly MTX, Monthly pulses of Vincristine and Steroid.Monthly pulses of Vincristine and Steroid.CNS prophylaxisCNS prophylaxis: Intrathecal chemo: Intrathecal chemoCNS TherapyCNS Therapy: RT + Int Systemic chemo: RT + Int Systemic chemoTesticular diseaseTesticular disease: RT: RT

ALL- PrognosisALL- Prognosis

Prognosis: WBC, Age, Cytogenetics Prognosis: WBC, Age, Cytogenetics – good if hyperdiploidy, trisomy 4,10,t (12,21)good if hyperdiploidy, trisomy 4,10,t (12,21)– Bad if Philadelphia chr t (9,22),t(4,11), t(8,14)Bad if Philadelphia chr t (9,22),t(4,11), t(8,14)

Immunophenotype: Pre-B, B, TImmunophenotype: Pre-B, B, TEarly response, Minimal residual disease (MRD)Early response, Minimal residual disease (MRD)Standard risk: 85 % survivalStandard risk: 85 % survivalHigh risk: 65 % survivalHigh risk: 65 % survivalVery low risk: 90% survivalVery low risk: 90% survivalInfants: 50 % survivalInfants: 50 % survivalEarly relapse is a poor signEarly relapse is a poor sign

Down Syndrome and LeukemiaDown Syndrome and Leukemia

10-20 fold increase10-20 fold increaseALL:AML 4:1ALL:AML 4:1< 2 years: M7 AML< 2 years: M7 AMLDS: 400 fold Increase in M7 AMLDS: 400 fold Increase in M7 AMLSuperior response to Rx of Superior response to Rx of AMLAMLTransient Myeloproliferative disorder in NB Transient Myeloproliferative disorder in NB which resolves within 3 months. which resolves within 3 months. – No clonal cytogenetic abnormalityNo clonal cytogenetic abnormality..

Rx : Exchange or low dose cytoreduction. Rx : Exchange or low dose cytoreduction. Higher chance of M 7 AML. (30% in some reports)Higher chance of M 7 AML. (30% in some reports)

Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia (AML)

20 % of all leukemias20 % of all leukemiasIncreased incidence in < 1 year of ageIncreased incidence in < 1 year of ageHigher incidence:Higher incidence:– Downs, Fanconi, Bloom, DBA, Kostmann, Downs, Fanconi, Bloom, DBA, Kostmann,

Neurofibromatosis I, Schwachman-DiamondNeurofibromatosis I, Schwachman-Diamond

Sx: Fever, bleeding, pallor, anorexia, fatigue, Sx: Fever, bleeding, pallor, anorexia, fatigue, Bone/Jt pain, LN, GI Sx.Bone/Jt pain, LN, GI Sx.Chloromas (green) – solid collection in bone/soft Chloromas (green) – solid collection in bone/soft tissuestissuesTypes: M0-M7, commonest M2Types: M0-M7, commonest M2M7- Downs syndromeM7- Downs syndrome

Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia (AML)

Treatment: Treatment: – Remission Induction, Consolidation, MaintRemission Induction, Consolidation, Maint– BMT (matched sib donor) after remission.BMT (matched sib donor) after remission.– ATRA (form of Vit A-transretinoic acid) in APMLATRA (form of Vit A-transretinoic acid) in APML

Results:Results:– HLA matched donor: 65 % EFSHLA matched donor: 65 % EFS– No donor 40-50 %No donor 40-50 %

Prognostic features:Prognostic features:– FavorableFavorable: t(8,21), inv(16); Early remission; : t(8,21), inv(16); Early remission;

FAB M4 with eosinophiliaFAB M4 with eosinophilia– UnfavorableUnfavorable: Monosomy 7; WBC> 100,000; : Monosomy 7; WBC> 100,000;

Secondary AML; Myelodysplasia with AMLSecondary AML; Myelodysplasia with AML

Hodgkin’s LymphomaHodgkin’s Lymphoma

Bimodal age distribution: first peak 20-30, again after Bimodal age distribution: first peak 20-30, again after age 50. Rare < 5 years.age 50. Rare < 5 years.5 % of all malignancies; 40 % of lymphomas, 5 % of all malignancies; 40 % of lymphomas, Sx: Painless adenopathy, 1/3 have “B” symptoms( fever, Sx: Painless adenopathy, 1/3 have “B” symptoms( fever, night sweats, wt loss)night sweats, wt loss)Pathology: Reed-Sternberg cell (large cell with Pathology: Reed-Sternberg cell (large cell with multilobed nuclei); B-cell, 4 subtypes.multilobed nuclei); B-cell, 4 subtypes.Rx: based on stage; Staging depends upon one side or Rx: based on stage; Staging depends upon one side or both sides of the diaphragm. Stage !-2, EFS 85-90 %, both sides of the diaphragm. Stage !-2, EFS 85-90 %, Stage 3-4; 75 % EFS.Stage 3-4; 75 % EFS.Second malignancy in patients who have recd Second malignancy in patients who have recd combination chemo and RT--combination chemo and RT-- Leukemia, NHL, Breast Leukemia, NHL, Breast cancer.cancer.

Non Hodgkins LymphomaNon Hodgkins Lymphoma

Most common lymphoma in childhoodMost common lymphoma in childhood10-15 % of all cancers (after leukemia, Brain tumor)10-15 % of all cancers (after leukemia, Brain tumor)50 % of all cancers in Africa (Burkitt’s)50 % of all cancers in Africa (Burkitt’s)More in males, CaucasiansMore in males, CaucasiansCommon in immunodeficiencies (SCID, Wiskott-Aldrich syndrome, Common in immunodeficiencies (SCID, Wiskott-Aldrich syndrome, HIV, following stem cell transplant.HIV, following stem cell transplant.Types: Types: – small, non-cleaved 40 % (B cell)small, non-cleaved 40 % (B cell)– Lymphoblastic lymphoma 30 % (T cells)Lymphoblastic lymphoma 30 % (T cells)– Large cell 20 % (B, T, indeterminate)Large cell 20 % (B, T, indeterminate)

Sites: Abdomen, mediastinum, head and neckSites: Abdomen, mediastinum, head and neckMajority are high gradeMajority are high gradeChromosomal translocations involve c-myc oncogene (chr 8)Chromosomal translocations involve c-myc oncogene (chr 8)

Burkitt’s LymphomaBurkitt’s Lymphoma

Endemic Burkitt’sEndemic Burkitt’s – African type, head and neck, African type, head and neck,

jawjaw– 95 % chance of EBV95 % chance of EBV

Sporadic Burkitt’sSporadic Burkitt’s – AbdomenAbdomen– 15-20 % chance of EBV15-20 % chance of EBV

Treatment- Early diagnosis, Treatment- Early diagnosis, surgery, chemotherapy, Tumor surgery, chemotherapy, Tumor lysis, Treatment based on lysis, Treatment based on stage and histology.stage and histology.Immunotherapy: Anti-CD 20 Immunotherapy: Anti-CD 20 monoclonal antibody; monoclonal antibody; (Rituximab)(Rituximab)Prognosis: Stage Overall 70 % Prognosis: Stage Overall 70 % cure rate, early 85 %.cure rate, early 85 %.

CaseCase

5 yr old boy with 5 yr old boy with progressive vomiting, progressive vomiting, headache, unsteady headache, unsteady gait and diplopia for 4 gait and diplopia for 4 weeks. MRI shows a weeks. MRI shows a contrast enhancing contrast enhancing tumor in the 4tumor in the 4thth ventricle with ventricle with obstructive obstructive hydrocephalus.hydrocephalus.

MedulloblastomaMedulloblastoma

-- most common CNS tumormost common CNS tumor

– Trt: Resection, Craniospinal RT, Chemo for Trt: Resection, Craniospinal RT, Chemo for incompletely resected tumor and infants to incompletely resected tumor and infants to permit smaller RT dose and recurrence.permit smaller RT dose and recurrence.

– Prognosis: Age, large size, degree of Prognosis: Age, large size, degree of resection, dissemination, histology.resection, dissemination, histology.

Brain TumorsBrain Tumors

20% of all malignancies in children20% of all malignancies in children

Age 3-7 yearsAge 3-7 years

Most often infratentorialMost often infratentorial– cerebellar and hemispheric astrocytoma, medulloblastoma, cerebellar and hemispheric astrocytoma, medulloblastoma,

brain stem gliomas, Craniopharyngiomas.brain stem gliomas, Craniopharyngiomas.

Sx: Persistent vomiting, headache, gait imbalance, Sx: Persistent vomiting, headache, gait imbalance, diplopia, ataxia, vision loss, school deterioration, growth diplopia, ataxia, vision loss, school deterioration, growth decelerationdeceleration

Inherited Genetic disorders Associated:Inherited Genetic disorders Associated:– Neurofibromatosis, Tuberous sclerosis, Von-Hippel-Lindau Neurofibromatosis, Tuberous sclerosis, Von-Hippel-Lindau

disease, Li-Fraumeni (glioma), Turcot syndromedisease, Li-Fraumeni (glioma), Turcot syndrome

A 13 year old female comes with A 13 year old female comes with complaints of headache off and on for the complaints of headache off and on for the past 2 months. Of significance, is that her past 2 months. Of significance, is that her shoe size has not changed for the past 3 shoe size has not changed for the past 3 years. She is Tanner stage 1.years. She is Tanner stage 1.

CT Scan shows a midline calcification in CT Scan shows a midline calcification in the brain.the brain.

What do you think is the diagnosis?What do you think is the diagnosis?

Observe the relatively homogeneous and cystic mass arising from the Observe the relatively homogeneous and cystic mass arising from the sella turcica and extending superiorly and posteriorly with compression sella turcica and extending superiorly and posteriorly with compression of normal regional structures. Note that the lesion is sharply demarcated of normal regional structures. Note that the lesion is sharply demarcated

and smoothly contoured.and smoothly contoured. CraniopharygiomaCraniopharygioma

Wilms TumorWilms Tumor

An 18-month-old girl is being evaluated because her An 18-month-old girl is being evaluated because her mother thinks her abdomen seems “full.” Physical mother thinks her abdomen seems “full.” Physical examination reveals an abdominal mass. examination reveals an abdominal mass. Ultrasonography identifies a solid renal mass. At Ultrasonography identifies a solid renal mass. At surgery, a stage I Wilms tumor is found.surgery, a stage I Wilms tumor is found.

This child’s chance of 4-year survival is CLOSEST to:This child’s chance of 4-year survival is CLOSEST to:

A.A. 30%30%B.B. 45%45%C.C. 60%60%D.D. 75%75%E.E. 95%95%

CT Scan -Wilms TumorCT Scan -Wilms Tumor

Wilms TumorWilms Tumor

Associations: WAGR (Wilms, Aniridia, GU Associations: WAGR (Wilms, Aniridia, GU anomalies, MR)anomalies, MR)– Beckwith-Weidemann syndrome- organomegaly, Beckwith-Weidemann syndrome- organomegaly,

Hemihypertrophy, omphalocoele)Hemihypertrophy, omphalocoele)

(chr 11p15.5 gene deletion)(chr 11p15.5 gene deletion)

3-5 % risk of WT (general population 8.5/mill)3-5 % risk of WT (general population 8.5/mill)– Denys-Drash: Pseudohermaphroditism, nephropathyDenys-Drash: Pseudohermaphroditism, nephropathy– Perlman syndrome: Macrocephaly, macrosomiaPerlman syndrome: Macrocephaly, macrosomia

Do US , UA q 3-4 monthsDo US , UA q 3-4 months

Wilms TumorWilms Tumor

HistologyHistology: favorable(FH) vs unfavorable : favorable(FH) vs unfavorable (UH)(UH)StagingStaging: I-local, II-excised, III-residual, IV-: I-local, II-excised, III-residual, IV-metastases, V -bilateralmetastases, V -bilateralTreatmentTreatment: Nephrectomy, Chemo-all, St I-: Nephrectomy, Chemo-all, St I-II-2 drugs-18 weeks, St III-IV- 3 drugs+ RTII-2 drugs-18 weeks, St III-IV- 3 drugs+ RTPrognosisPrognosis: : – FH: > 90% at 2 yearsFH: > 90% at 2 years– UH: < 60% at 2 yearsUH: < 60% at 2 years

QuestionQuestion

A 9 year old previously healthy girl manifests A 9 year old previously healthy girl manifests progressive painless proptosis and decreased progressive painless proptosis and decreased visual acuity of the left eye during a 2 month visual acuity of the left eye during a 2 month period. The most likely diagnosis isperiod. The most likely diagnosis is

1.1. Pseudotumor of the orbitPseudotumor of the orbit

2.2. TrichinosisTrichinosis

3.3. RetinoblastomaRetinoblastoma

4.4. RhabdomyosarcomaRhabdomyosarcoma

5.5. Orbital cellulitisOrbital cellulitis

RhabdomyosarcomaRhabdomyosarcoma

7 % of all childhood cancers7 % of all childhood cancersPainless non tender mass, 60% under age 6Painless non tender mass, 60% under age 6Sites: head & neck, GU, Extremities, mets lungs.Sites: head & neck, GU, Extremities, mets lungs.Majority sporadic, associations: B-W, Li Fraumeni, NF 1Majority sporadic, associations: B-W, Li Fraumeni, NF 1Types:Types:– Embryonal 70%,Embryonal 70%, better prognosis better prognosis– Alveolar 30 %,Alveolar 30 %, trunk, worse prognosis trunk, worse prognosis

Treatment: Surgery, Chemo, local control RTTreatment: Surgery, Chemo, local control RTResults: Results: – 85 % good risk85 % good risk– 30 % metastatic disease30 % metastatic disease

MassMassThe mother of a 22-month-old The mother of a 22-month-old boy reports that he has been boy reports that he has been fussy and tired. Findings on fussy and tired. Findings on physical examination confirm physical examination confirm the presence of a nontender rt the presence of a nontender rt upper quadrant mass. Bilateral upper quadrant mass. Bilateral periorbital ecchymoses also periorbital ecchymoses also are noted.are noted.Of the following, the MOST Of the following, the MOST likely cause for these findings likely cause for these findings isisA.A. multicystic kidney multicystic kidney diseasediseaseB.B. neuroblastomaneuroblastomaC.C. non-Hodgkin non-Hodgkin lymphomalymphomaD.D. HepatoblastomaHepatoblastomaE.E. Wilms tumorWilms tumor

NeuroblastomaNeuroblastoma

The mother of a 22-month-old boy reports that he has The mother of a 22-month-old boy reports that he has been fussy and tired. Findings on physical examination been fussy and tired. Findings on physical examination confirm the presence of a nontender left upper quadrant confirm the presence of a nontender left upper quadrant mass. Bilateral periorbital ecchymoses also are noted.mass. Bilateral periorbital ecchymoses also are noted.

Of the following, the MOST likely cause for these Of the following, the MOST likely cause for these findings isfindings is

A.A. multicystic kidney diseasemulticystic kidney diseaseB.B. neuroblastomaneuroblastomaC.C. non-Hodgkin lymphomanon-Hodgkin lymphomaD.D. HepatoblastomaHepatoblastomaE.E. Wilms tumorWilms tumor

NeuroblastomaNeuroblastoma

Most common extra-cranial solid tumorMost common extra-cranial solid tumorMost common cancer in the first year of lifeMost common cancer in the first year of lifeFrequent in <4 years, 97 % by 10 yearsFrequent in <4 years, 97 % by 10 yearsMost commonly diagnosed as Stage III or IVMost commonly diagnosed as Stage III or IVDx: biopsy or BM plus urine for VMA, HVADx: biopsy or BM plus urine for VMA, HVAMetastatic- orbital discoloration, bone painMetastatic- orbital discoloration, bone painPrognosis: StagePrognosis: Stage– Better in age < 1 year, low stage, Shimada Better in age < 1 year, low stage, Shimada

classification (histology), high DNA index.classification (histology), high DNA index.– Worse with N-myc oncogene amplification and tumor Worse with N-myc oncogene amplification and tumor

diploidy (DNA index 1), Higher LDH, Ferritin, age >1.diploidy (DNA index 1), Higher LDH, Ferritin, age >1.

NeuroblastomaNeuroblastoma

Low risk:Low risk:– Surgery alone; >95 % 5 year survival Surgery alone; >95 % 5 year survival

Intermediate risk:Intermediate risk:– Surgery and Chemo; 80-90 % 5 year survivalSurgery and Chemo; 80-90 % 5 year survival

High risk:High risk:– Induction chemo, surgery, Chemo with autologous Induction chemo, surgery, Chemo with autologous

transplant, RT, Biologic therapytransplant, RT, Biologic therapy– 30 % 5 year survival30 % 5 year survival

Stage Stage IVs-Localized Prim tumor with spread to skin, IVs-Localized Prim tumor with spread to skin, liver and/or bone marrow- Minimal therapy.liver and/or bone marrow- Minimal therapy.

A 16 year old male comes in because he A 16 year old male comes in because he fell in the supermarket.fell in the supermarket.

P/E shows a small painless mass on the P/E shows a small painless mass on the medial aspect of the knee.medial aspect of the knee.

X ray shows a fracture and a lytic sunburst X ray shows a fracture and a lytic sunburst pattern. (periosteal elevation)pattern. (periosteal elevation)

What is your diagnosis?What is your diagnosis?

What would you do next?What would you do next?

Osteogenic Sarcoma-Osteogenic Sarcoma- X ray and MRI X ray and MRI

Osteogenic SarcomaOsteogenic Sarcoma

MRI, Bone scan, Biopsy, CT Chest. MRI, Bone scan, Biopsy, CT Chest. Peak incidence- 2Peak incidence- 2ndnd decade decadePredisposition: Hereditary retinoblastomas, Li-Predisposition: Hereditary retinoblastomas, Li-Fraumeni, Pagets, RT, Alkylating agentsFraumeni, Pagets, RT, Alkylating agents60 % near the knee (Metaphyses of long bones)60 % near the knee (Metaphyses of long bones)History of fall, pain common Sx, mass, no History of fall, pain common Sx, mass, no systemic Sx.systemic Sx.Treatment: Open biopsy, Sperm banking, Neo-Treatment: Open biopsy, Sperm banking, Neo-adjuvant Chemotherapy, limb preserving adjuvant Chemotherapy, limb preserving surgery.surgery.

A 16 year old Caucasian A 16 year old Caucasian female comes with complaints female comes with complaints of chest pain and difficulty of chest pain and difficulty breathing for the past one breathing for the past one week. She has had fever, wt week. She has had fever, wt loss over the last 2 months. loss over the last 2 months. She has reduced air entry and She has reduced air entry and CXR shows a moth eaten CXR shows a moth eaten appearance of one of the ribs appearance of one of the ribs and a pleural effusion.and a pleural effusion.Biopsy is done and is Biopsy is done and is consistent with Ewings consistent with Ewings Sarcoma.Sarcoma.

Ewing’s SarcomaEwing’s Sarcoma

Seen in Axial bones, flat bones and long bones. Seen in Axial bones, flat bones and long bones. 20 % in soft tissue.20 % in soft tissue.Caucasians, Onion skin appearance, Diaphysis Caucasians, Onion skin appearance, Diaphysis affected.affected.MRI, CT Chest, Bone scan, Biopsy, BM aspirate MRI, CT Chest, Bone scan, Biopsy, BM aspirate and biopsy( Anemia).and biopsy( Anemia).Unique marker: t(11,22) most casesUnique marker: t(11,22) most casesPNET: Ewing like tumor with neural PNET: Ewing like tumor with neural differentiationdifferentiationTreatment:Treatment:– Surgery, RT, Neoadjuvant Chemo,Surgery, RT, Neoadjuvant Chemo,

Ewing’s SarcomaEwing’s Sarcoma

RetinoblastomaRetinoblastoma

Presentation:Presentation:– Leukocoria (cats eye reflex),Dilated pupil, esotropia, strabismusLeukocoria (cats eye reflex),Dilated pupil, esotropia, strabismus

Unilateral 75 % (could be hereditary/non)Unilateral 75 % (could be hereditary/non)– 60 %60 % unilateral and unilateral and non hereditarynon hereditary– 15 % unilateral and 15 % unilateral and hereditary (RB1 mutation)hereditary (RB1 mutation)

Bilateral 25 %Bilateral 25 %– 25 % are bilateral and hereditary, have 25 % are bilateral and hereditary, have RB1RB1 mutation mutation– Earlier age, 11mos, Can develop in each eye separatelyEarlier age, 11mos, Can develop in each eye separately– Higher incidence of sarcoma, melanoma, brain tumors.Higher incidence of sarcoma, melanoma, brain tumors.

10 % of retinoblastoma cases have family history.10 % of retinoblastoma cases have family history.But child of parent with the RB1 gene (Chromosome But child of parent with the RB1 gene (Chromosome 13q) has a 45 % chance of developing the tumor.13q) has a 45 % chance of developing the tumor.

RetinobalstomaRetinobalstoma

Tumor lysis syndromeTumor lysis syndrome

A 12 year old girl with ALL has been started on A 12 year old girl with ALL has been started on Chemotherapy. She had a WBC of 82,000, Hb Chemotherapy. She had a WBC of 82,000, Hb 9gm, Platelet count of 45,000. Within 12 hours, 9gm, Platelet count of 45,000. Within 12 hours, she develops findings typical of tumor lysis she develops findings typical of tumor lysis syndrome:syndrome:Which one of the following depicts itWhich one of the following depicts it

1.1. K high, P high, K high, P high, LDH normal, Na highLDH normal, Na high2.2. K high, P nl, K high, P nl, LDH high, LDH high, Na nlNa nl3.3. K nl, K nl, P high, P high, LDH high,LDH high, Na high Na high4.4. K nl, K nl, P nl, P nl, LDH high, LDH high, Na nlNa nl5.5. K high, P high, K high, P high, LDH high, LDH high, Na nl.Na nl.

Tumor lysis syndromeTumor lysis syndrome

5.5.

Rapid destruction of cancer cells.Rapid destruction of cancer cells.

Release of intracellular ions, also Uric Release of intracellular ions, also Uric acid, can cause tubular obstruction and acid, can cause tubular obstruction and damage.damage.

Treatment: Allopurinol or Rasburicase Treatment: Allopurinol or Rasburicase early, Hydration, alkalinization, diuretic early, Hydration, alkalinization, diuretic therapy, therapy,

Chemotherapy-Side effectsChemotherapy-Side effects

Anthracyclines: CardiomyopathyAnthracyclines: CardiomyopathyVincristine: foot drop, neurologicalVincristine: foot drop, neurologicalCisplatinum: kidney, deafnessCisplatinum: kidney, deafnessMethotrexate, 6MP: Liver toxicityMethotrexate, 6MP: Liver toxicityBleomycin: Pulmonary fibrosisBleomycin: Pulmonary fibrosisAsparaginase: PancreatitisAsparaginase: PancreatitisCyclophosphamaide: Hemorrhagic cystitisCyclophosphamaide: Hemorrhagic cystitis– (MESNA, Uroprotector)(MESNA, Uroprotector)

Fever, NeutropeniaFever, Neutropenia

Single most important risk factor: ANCSingle most important risk factor: ANC

Organisms: Gram negative, Staph epi in Organisms: Gram negative, Staph epi in catheter patientscatheter patients

Medication: Broad spectrum 3Medication: Broad spectrum 3rdrd generation generation antibioticsantibiotics

Anti-fungal after 4 daysAnti-fungal after 4 days

Examine patient thoroughlyExamine patient thoroughly

Late effectsLate effects

A 16-year-old girl, diagnosed at 8 years of age as having A 16-year-old girl, diagnosed at 8 years of age as having Hodgkins disease, completed therapy with Involved field Hodgkins disease, completed therapy with Involved field RT and chemotherapy. She now develops petechiae, RT and chemotherapy. She now develops petechiae, purpura, LN, HSM. Lab include: plt 12,000/mm³; Hb 8.0 purpura, LN, HSM. Lab include: plt 12,000/mm³; Hb 8.0 gm/dL; and WBC 13,000/mm³.gm/dL; and WBC 13,000/mm³.

The MOST likely explanation for these findings isThe MOST likely explanation for these findings isA.A. acute myeloid leukemia as a second acute myeloid leukemia as a second malignancymalignancyB.B. disseminated varicelladisseminated varicellaC.C. drug-induced immune thrombocytopenic purpuradrug-induced immune thrombocytopenic purpuraD.D. late-onset aplastic anemia due to chemotherapylate-onset aplastic anemia due to chemotherapyE.E. viral-induced immune thrombocytopenic purpuraviral-induced immune thrombocytopenic purpura

Late effectsLate effects

You are evaluating a 9 year old child for short You are evaluating a 9 year old child for short stature. She was treated at 3 yrs of age for stature. She was treated at 3 yrs of age for ALL, received cranial RT. Her height is < 5ALL, received cranial RT. Her height is < 5 thth percentile and she is Tanner stage I. Of the percentile and she is Tanner stage I. Of the following , the test MOST likely to be abnormal following , the test MOST likely to be abnormal is measurement ofis measurement of

1.1. EstradiolEstradiol2.2. Follicle stimulating hormoneFollicle stimulating hormone3.3. Gonadotropin releasing hormoneGonadotropin releasing hormone4.4. Growth hormoneGrowth hormone5.5. Thyroid stimulating hormoneThyroid stimulating hormone

Late effects of cancer therapyLate effects of cancer therapy

RT:RT: Hypothalamic pituitary axis is impaired; Hypothalamic pituitary axis is impaired;

central hypothyroid and Adrenal insuff.central hypothyroid and Adrenal insuff. RT doses higher in brain tumorRT doses higher in brain tumor GH is dose sensitive to the effects of GH is dose sensitive to the effects of

RT RT Age related: < 5 years susceptibleAge related: < 5 years susceptible Panhypopit with higher dosesPanhypopit with higher doses ovarian failure with RTovarian failure with RT

ChemotherapyChemotherapy

A 16 year old boy is receiving chemo for A 16 year old boy is receiving chemo for rhabdomyosarcoma. The treatment involves rhabdomyosarcoma. The treatment involves one year of repeated cycles of Vincristine, one year of repeated cycles of Vincristine, Actinimycin-D and Cyclophosphamide.Actinimycin-D and Cyclophosphamide.The most likely endocrinologic late effect of this The most likely endocrinologic late effect of this therapy istherapy is1.1. Growth hormone deficiencyGrowth hormone deficiency2.2. HypothyroidismHypothyroidism3.3. ImpotenceImpotence4.4. InfertilityInfertility5.5. OsteoporosisOsteoporosis

Chemotherapy effectsChemotherapy effects

InfertilityInfertility

Chemotherapy with alkylating agents Chemotherapy with alkylating agents Females,less effects than males; normal Females,less effects than males; normal

puberty, early menopause.puberty, early menopause.Males; irreversible gonadal toxicity and Males; irreversible gonadal toxicity and

sterility with azospermia. Puberty usually sterility with azospermia. Puberty usually not affected (leydig cells)not affected (leydig cells)

TransplantTransplant

The most consistent finding observed in The most consistent finding observed in nearly all large cooperative group studies nearly all large cooperative group studies that have tested matched family donor that have tested matched family donor hematopoietic stem cell transplantation hematopoietic stem cell transplantation (HSCT) for children with AML is:(HSCT) for children with AML is:1.1.HSCT reduces disease-free survivalHSCT reduces disease-free survival2.2.HSCT improves disease-free survivalHSCT improves disease-free survival3.3.HSCT improves event-free survivalHSCT improves event-free survival4.4.HSCT improves overall survivalHSCT improves overall survival

TransplantTransplant

The most common reason for the failure The most common reason for the failure of hematopoietic stem cell of hematopoietic stem cell transplantation is:transplantation is:

1.1. Veno-occlusive disease of the liverVeno-occlusive disease of the liver

2.2. Disease recurrenceDisease recurrence

3.3. InfectionInfection

4.4. Graft vs. host diseaseGraft vs. host disease

5.5. Graft rejectionGraft rejection

GVHD ( Graft vs Host disease)GVHD ( Graft vs Host disease)

True statements include all except:True statements include all except:1.1. It is the reaction of the donor lymphocytes It is the reaction of the donor lymphocytes

against the host.against the host.

2.2. Acute GVHD starts within the first 100 days Acute GVHD starts within the first 100 days and chronic is after 100 days.and chronic is after 100 days.

3.3. Affects the skin, liver and GI tractAffects the skin, liver and GI tract

4.4. Irradiation of blood products does not helpIrradiation of blood products does not help

5.5. Complete HLA matching prevents GVHDComplete HLA matching prevents GVHD

Germ cell tumorsGerm cell tumors

2-3 % of Pediatric malignancies2-3 % of Pediatric malignancies

Teratomas arise from endoderm, Teratomas arise from endoderm, ectoderm and mesodermectoderm and mesoderm

Markers:Markers:– Endodermal sinus tumors –Alpha feto proteinEndodermal sinus tumors –Alpha feto protein– Embryonal Ca, Choriocarcinoma- HCGEmbryonal Ca, Choriocarcinoma- HCG

Mature teratomas- excision onlyMature teratomas- excision only

Immature Teratomas: Surgery + ChemoImmature Teratomas: Surgery + Chemo

Other topics- do readOther topics- do read

HistiocytosisHistiocytosis

Storage disordersStorage disorders

GOOD LUCKGOOD LUCK