Corticosteroid induced tumor lysis syndrome in acute lymphoblastic leukemia

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  • 66 Letters and Correspondence

    A New Case of Passovoy Defect

    To the Editor: Passovoy defect is a rare inherited coagulation defect charac- terized by a haemorrhagic diathesis and a prolonged activated partial throm- boplastin time (APTT) not due to the deficiency of any of the known clotting factors [l]. Only five kindreds have been reported so far [ I ,2]. It is not completely understood whether the defect is transmitted in an autoso- ma1 dominant or recessive fashion [2]. Mild to moderate bleeding symp- toms were reported and replacement with fresh-frozen plasma has been successful for the control of bleeding.

    We describe here a new case of Passovoy defect, with apparent recessive inheritance,

    A 28-year-old healthy male was referred after a surgical removal of a tendinous cyst of his left vastus lateralis muscle was followed by enlarging muscle haenlatoma developing 2 days after intervention. Surgical drainage was placed for 4 days, with apparent resolution. One week later haematoma recurred with heavy bleeding of partially clotted blood from a new surgical drainage. Haemoglobin fell from 14.5 to 10.2 g/dl. Eight units of fresh- frozen plasma was required to control the bleeding. After 5 days bleeding recurred and 1 I of fresh-frozen plasma for 3 days was required to definitely stop the haemorrhage. A routine screening before surgery and coagulation tests during hospitalization revealed a mild prolongation of APTT, not considered by the attending physicians. Five years before, profuse gingival bleeding after dental devitalization occurred and local compressive package was required. The patient did not report tooth extraction or surgical inter- vention. The parents and the sister of the propositus were completely asymptomatic.

    were in the normal range. All these assays were normal also in the parents and the sister.

    Normal and patient plasma mixture, immediately and after 2 hr of incu- bation, yielded a normal APTT, excluding any inhibitory effect. The pa- tient's ATPP remained unchanged after the addition of Passovoy deficient plasma (obtained from one of the original patients reported on by Hougie and provided by George King Biomedical, Salem, MA), thus leading to the diagnosis of Passovoy defect. The addition of as little as 10% of normal plasma was sufficient to significantly shorten the patient's APTT (Table I ) . Normal pooled plasma adsorbed with aluminum hydroxide retained the ability to normalize the A R T of the patient and Passovoy plasma, thus confirming that Passovoy factor is not or is only poorly adsorbed by alunii- num hydroxide 121 (Table I ) . Prolonged incubation of the propositus plasma (10 min) did not normalize the APTT (ratio to normal plasma 1.29), as already observed by Hougie et al. [ I ] . The main laboratory findings are summarized in Table I .

    Our case is similar to the cases reported by Hougie et al. [ I ,2] as to the clinical and laboratory manifestations. This new case adds to the evidence of a linkage between Passovoy defect and the presence of haemorrhagic symptoms. In our case a recessive inheritance is suggested by the clinical and laboratory normality of the parents of the propositus, but the lack of a quantitative assay for Passovoy factor and molecular genetic probes does not allow any definite conclusion. Further studies are needed in order to evaluate the role of Passovoy factor in haemostasis,


    FRANCESCO RODEGHIERO Department of Haematology, Haemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy

    . . On 717 different occasions the patient revealed consistently prolonged

    APTT (ratio to normal APTT always higher than I .3). The parents and the sister had normal APTT.

    Prothrombin time, thrombin time, fibrinogen level, and Platelet Count were consistently normal. All coagulation factors (including contact-phase factors and factor XIIl), ristocetin cofactor, and alfa-2-antiplasmin were in

    ing time (Simplate 11) was normal (6 min; normal below 8 min). Platelet aggregation with ADP, adrenaline, collagen, arachidonic acid, and ristoce- tin were normal. Serotonin and ATPiADP content of platelet &granules

    I . Hougie C , McPherson RA, Brown JE, Lakin-Thomas PL, Melaragno A, Aronson L, Baugh RF: The Passovoy defect. Further characterization of a hereditary hem- orrhagic dbdtheSiS. N Engl J Med 298: 1045-1048. 1978.

    2. Hougie C. McPherson R A , Aronson L: Passovoy factor: A hitherto unrecognised the normal range. Antiphospholipid antibodies were not detectable, Bleed- factor necessary for haemostasis. Lancet 2:290-291, 1975.

    TABLE I. APTT of Patient's Plasma and Correction Studies*


    Kaolin" Ratio Silicah Ratio

    Normal pool Propositus Passovoy plasma Normal/propobitus Normal/Passovoy Passovoyipropositus 10% normali90% propositus 25% normal/75% propositus Normdl/normal" Normalipropositus' Normal'ipropositus Norma~'lPabS0VOy Normal/Pasaovoy'

    38"4 54"4 58"3 40" I 42" 54"5 45" 4 0 5 55" 6 0 4 6 0 8 6 0 7 62"


    43"s 1.42 62"2 I .42 1.52 67"1 I .53 I .04 4 6 2 I .05 1.09 4 6 8 I .07 I .42 6 6 3 1.51 1.18 5 l"3 1.17 I .05 45" I 0 3

    6 0 64" 63"X 67" 6 6

    *The results reprcsent the mean ot at least three separate determinations. "Kaolin from Stago, Asnieres, France. hMicronized silica from lnstrumentational Laboratory, Milano. Italy. 'Plasma (700 111) was adsorbed with 50 111 of aluminum hydroxide, incubated for 5 min at 37C and then centrifuged for 10 min at 1,500g.

    Corticosteroid Induced Tumor Lysis Syndrome in Acute Lyrnphoblastic Leukemia

    To the Editor; We report the occurrence of massive tumor lysis and renal failure in a 35-year-old woman with acute lymphoblastic leukemia (ALL) of T-cell origin after a single dose of prednisone. This patient presented with bilateral breast lumps, supraclavicular lymphadenopathy, and increas- ing shortness of breath. She had no fevers, chills, sweats, or weight loss. On physical examination, the patient had a respiratory rate of 20/min, blood pressure of 180195, pulse of 901min, and temperature of 37C. There was dullness to percussion over the left chest with decreased air entry on the left. The neurological and cardiovascular exams were normal. The spleen was not palpable but moderate hepatomegaly was present.

    Laboratory investigations revealed a hemoglobin of 142 gi l , white cell count of 34.3 gil with 10% blasts and 18% abnormal lymphoid cells. The platelet count was 242 gil. The serum chemistry was as follows: potassium 4.0 mEqil, phosphorus 1.49 mmolil, urea 12.0 mmolil, creatinine 307 pmolil, uric acid 7 15 pmolil, and LDH 7 15 U/I. Urine analysis revealed no abnormalities. Blast cells were found in the CSF. A thoracentesis revealed blasts in the pleural fluid. Bone marrow morphology was consistent with L2 ALL. Immunocytochemistry demonstrated that the tumor cells were CD 45, CD 3 positive, and CD 20, CD 30 negative, confirming the presence of a leukemia of T-cell lineage.

  • Letters and Correspondence 67

    had been diagnosed. Desferrioxamine chelation treatment had not been suspended during this fever state.

    At admission the patient appeared well but had a temperature of 39C. Desferrioxamine treatment was suspended. On the day of admission plas- modium fakiparum-ring forms and gametocytes were identified in thin blood film. Parasitemia was 20,000immc. Chloroquine resistance became manifest but quinine sulphate treatment achieved negative parasitemia 7, 14, and 28 days after beginning the treatment. One of the patients blood donors was identified as the infection source.

    In our case the mild course of the disease for a non-immune subject, despite the delay in diagnosis, was surprising. The mildness of the patients clinical picture was not related to her genetic red cell defect because she survived on blood donors erythrocytes.

    The desferrioxamine treatment alone, at 50 mgikglday ( 1 gi24 hr) for 6 daysiweek (not suspended during febrile state until malaria was diagnosed) may have been responsible for an anti-plasmodium falciparum effect in our patient.

    As soon as the diagnosis was made the patient was started on a sodium bicarbonate infusion. Due to a previous hypersensitivity reaction to allopu- rinol, this drug was not used. Instead, ibuprofen was employed to reduce uric acid induced renal damage. Prednisone 35 mg twice daily was started the day prior to planned chemotherapy with daunomycin, L-asparaginase, vincristine, and prednisone (LAVP).

    Twelve hours after prednisone was initiated, the patient became oliguric with evidence of renal failure and serum chemistry as follows: phosphorous 5.92 mmolil, potassium 4.1 mEqil, urea 25.2 mmolil, creatinine 244 pmolil, and uric acid 1,464 p,mol/l. Hemodialysis was initiated the same day and continued for 3 consecutive days after which a rapid recovery of renal function and electrolyte balance occurred.

    Chemotherapy with the LAVP protocol continued after completion of dialysis along with CNS treatment using cytosine arabinoside and meth- otrexate via an Ommaya reservoir. A bone marrow aspirate and biopsy, thoracentesis, and CSF analysis done 2 months post-initiation of induction treatment showed no evidence of residual disease.

    The acute tumor lysis syndrome is a well-recognized complication of cytoreductive therapy for rapidly proliferating neoplasms. This clinical picture is usually seen after chemotherapy is employed in the treatment of non-Hodgkins lymphomas and leukemias [ 141. Although cortico- steroid-induced acute tumor lysis has previously been identified in the non-Hodgkins lymphomas, the occurrence of massive tumor lysis in T-cell ALL after corticosteroid administration is not a well-recognized clinical entity. This case, therefore, illustrates the complications that may arise in administering corticosteroids to these patients. The early use of alkaline diuresis and, if necessary, hemodialysis, can however produce excellent clinical results without delaying the initiation of chemotherapy.


    H.A. MESSNER Princess Margaret Hospital, Toronto, Ontario


    I, Dhingra K , Newcom SR: Acute tumor lysis syndrome in non-Hodgkin lymphoma induccd by dexamethasone. Am J Hematol29: 115-1 16. 1988.

    2. Sparano J , Ramircz M, Wiemik PH: Increasing recognition of corticosteroid- induced tumor lysis syndrome in non-Hodgkins lymphoma. Cancer 65: 1072- 1073, 1990.

    3. Hailer C, Dhadly M: The tumor lysis syndrome. Ann lntem Med I14:808-809, 1991.

    4. Loosvcld OJ, Schouten HC, Gaillard CA. Blijham GH: Acute tumor lysis syn- drome in a patient with acute lymphoblastic leukemia after a single dose of prednisone. BrJ Haematol 77:122-123, 1991

    Desferrioxamine in the Treatment of Plasmodium Falciparum Malaria

    To the Editor: We read with interest the preliminary report by Traore et al. 111 o n the use of desferrioxamine in the treatment of plasmodium falci- parum malaria in humans. Their results ai-e encouraging and agree with results previously obtained in vitro [2,3].

    Recently we observed a post-transfusion malaria case in a 7-year-old Italian girl affected by thalassemia major. The patient was admitted to our Division with a 30 day history of fever of unknown origin. She had a slight increase of preexisting hepatosplenomegaly and an increased requirement for blood transfusion. Her general, nutritional, and psychological condi- tions were satisfactory. Case history was negative for foreign travel.

    She had been undergoing regular transfusion and iron chelation with desferrioxamine (50 mgikgiday for 6 daysiweek) since thalassemia major


    ROSARIO Russo Department of Pediatric Hematology,

    Department of Infectious Diseases, University of Catania, Catania, Italy

    REFERENCES I . Traore 0, Carnevale P, Kaptue-Noche L, MBede J , Desfontaine M, Elion J ,

    Labie D, Nagel RL: Preliminary report on the use of desferrioxamine in the treatment of plasmodium falciparum malaria. Am J Hematol 37:206, 1991.

    2. Raventos-Suarez C, Pollack S , Nagel RL: Plasmodium falciparum: Inhibition of in vitro growth by desferrioxamine. Am J Trop Med Hyg 3 I (5):919, 1982.

    3. Peto TEA, Hershko C: Iron and infection. In Iron Chelating Therapy. Baillieres Clinical Haematology, 1989, p 435.

    Immune Bernard Soulier-Like Syndrome Associated With Anti-Glycoprotein-lX Antibody

    To the Editor: We wish to describe a patient who developed a functional platelet defect, mediated by an autoantibody directed specifically to GPIX. Bernard Soulier Syndrome (BSS) is a rare inherited bleeding disorder in which thrombocytopenia with giant platelets and prolonged bleeding time are found [ 11. The platelet defect in BSS has been attributed to the absence of glycoprotein Ib-IX (GP Ib-IX), which serves as a receptor for von Willebrand factor (vWF) [2].

    A 75-year-old woman was referred to the hematology clinic for evalua- tion of thrombocytopenic purpura. Physical examination on admission re- vealed purpura on both calves and a slightly enlarged liver. Laboratory tests disclosed: Hb I 1 gidl, WBC 3,5OO/kI, a platelet count of 70,OOOikl and a hypercellular bone marrow with numerous (normal and small forms) mega- karyocytes. Coagulation tests were normal except for a bleeding time (Dukes) of 8 min (normal range up to 4 min), and a lack of platelet agglutination in response to ristocetin. An increased platelet associated immunoglobulin (PAlg 30 ngi106 platelets, normal range 0-10 ngilO platelets) directed our attention to a possible immune cause for the defect of the patients platelets. The combination of pancytopenia and hypercellular bone marrow suggested that this patient had myelodysplastic syndrome (MDS). The relation between the MDS and the immune thrombocytopenic purpura (ITP) remained unsolved. She died 3 years after her first examina- tion due to a sepsis.