childhood acute lymphoblastic leukemia: risk stratification in developing countries shripad banavali...
TRANSCRIPT
![Page 1: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/1.jpg)
Childhood Acute
Lymphoblastic Leukemia: Risk Stratification in
Developing Countries
Shripad BanavaliMD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA)
Tata Memorial Hospital
![Page 2: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/2.jpg)
Acute Lymphoblastic Leukemia
• Most common form of childhood cancer.
• Treatment of ALL is true success story of modern oncology.
![Page 3: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/3.jpg)
![Page 4: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/4.jpg)
Key Components of Successful Therapy
• Clinical trials; Co-operative groups• Empiric multi-agent CNS therapy• Pre-symptomatic CNS therapy• Post-induction intensification
– Anti-metabolite therapy– Re-induction/re-consolidation
Risk adapted therapy
![Page 5: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/5.jpg)
ALL: L1, L2, L3, PAS
![Page 6: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/6.jpg)
![Page 7: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/7.jpg)
![Page 8: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/8.jpg)
![Page 9: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/9.jpg)
Multiplex RT-PCR in B lineage ALL
![Page 10: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/10.jpg)
![Page 11: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/11.jpg)
![Page 12: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/12.jpg)
MORPHOLOGICAL REMISSION (98%)
• Morphology cannot discriminate between patients with HR or LR of relapse.
• More sensitive techniques needed to detect small numbers of malignant cells during and after treatment.
• Detection of MRD (IP and RT-PCR).
MOLECULAR REMISSION (?%)
![Page 13: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/13.jpg)
What is detection of MRD
![Page 14: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/14.jpg)
What is detection of MRD
It is nothing but detection of the clones of cells resistant to the chemotherapy given.
![Page 15: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/15.jpg)
MRD: Study of Resistance in ALL
Resistance can also be studied by:-
(1) MTT in-vitro Assay
Pred + Asp + VCR Drug resistance profile
3 yr DFS 100% Most sensitive profile (20% pts)
84% Inter. sensitive profile (40% pts)
43% Least sensitive profile (40% pts)
![Page 16: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/16.jpg)
MRD: Study of Resistance in ALL
Resistance can also be studied in-vivo by:-
(2) D7 blast count post exposure to
Pred + 1 dose of IT-MTX
(3) D 15 BM blast %
![Page 17: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/17.jpg)
![Page 18: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/18.jpg)
Estimation of MRD
(1) Flow cytometry :
(2) RT-PCR:
![Page 19: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/19.jpg)
![Page 20: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/20.jpg)
![Page 21: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/21.jpg)
![Page 22: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/22.jpg)
Treatment of Childhood ALL
TOP PRIORITY
PREVENTION OF RELAPSE
![Page 23: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/23.jpg)
ALL-Challenges For Developed CountriesClinical trials
• Despite success, 25% of children relapse. Intensify therapy for those who need or will benefit from it.
• Many of those who are cured are over-treated Minimize side effects
• Little progress has been made in the treatment of certain very high risk groups (Ph+, infants and relapse)
Develop new treatment options
![Page 24: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/24.jpg)
![Page 25: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/25.jpg)
![Page 26: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/26.jpg)
PEDIATRIC ONCOLOGY : FACTS
India U.S.A.
• New cases / yr 44,000 12,400
• Rx, curative intent <25% 100%
• Cure rate, adequ. Rxed 50% 70%
• Overall cure rate 12% 70%
• Rxed on Co-op Groups 1% 98%
![Page 27: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/27.jpg)
Hematological cancers in IndiaAverage Annual Age standardized incidence rate per
100,000 persons (1990-1996)
Region Lymphoid leukemia Myeloid leukemia
M F M F
Delhi 2.3 1.2 2.3 1.9
Mumbai 1.8 1.1 2.0 1.6
Bangalore 1.2 0.8 1.8 1.7
Chennai 1.7 1.0 1.4 1.2
Bhopal 1.4 0.3 1.8 1.4
Barshi 1.0 0.5 1.4 0.7
Medical Oncology, vol. 19, 141-150, 2002
![Page 28: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/28.jpg)
Rx of ALL: THE TMH EXPERIENCE
V+P1 -------------------------------22%
V+P+Doxo or L-Asp2-------------32%
VACP3------------------------------30%
1. Advani et al: Am J Hematol 15:35,1983
2. Advani et al: Ind J Cancer 26:180,1989
3. Advani et al: Am J Hematol 39:242, 1992
4. Advani et al: Ann Onc 10:167,1999
![Page 29: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/29.jpg)
Acute Lymphoblastic Leukemia (MCP 841)
DFS 1986-89
YEARS
14121086420
Su
rviv
al
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
DFS 47.4 %
Acute Lymphoblastic Leukemia (MCP 841)
DFS 1990-94
YEARS
121086420
Su
rviv
al
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
DFS 54.18 %
Acute Lymphoblastic Leukemia (MCP 841)
DFS 1995-98
YEARS
76543210
Su
rviv
al
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
DFS 58.2 %
Acute Lymphoblastic Leukemia (MCP 841)
DFS (1986-98)
YEARS
14121086420
Su
rviv
al
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
DFS 54.0 %
![Page 30: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/30.jpg)
Advani et al. Ann Oncol 1999
![Page 31: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/31.jpg)
Advani et al. Ann Oncol 1999
![Page 32: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/32.jpg)
Clinical characteristics in relationship to event free survival by participating center. Results of multi-variate analysis.
Characteristic DELHI
P-Value
CHENNAII
P-Value
MUMBAI
P-Value
Number accrued 228 168 652
Age 0.20 0.033 0.74
WBC count 0.0005 0.080 0.002
Platelet count 0.025 0.059 0.011
Hemoglobin 0.94 0.38 0.79
LDH -- 0.47 0.39
Immunophenotype 0.99 0.13 0.17
Lymphadenopathy 0.66 0.83 0.49
Hepatosplenomegaly 0.58 0.13 0.92
Mediastinal mass 0.32 0.10 0.92
![Page 33: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/33.jpg)
CALLA + ACUTE LYMPHOBLASTIC LEUKEMIA
CHANGING INCIDENCE OVER 3 DECADES
0%
10%
20%
30%
40%
50%
60%
70%
80%
Mumbai Delhi Chennai
1980s
1990s
2000s
![Page 34: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/34.jpg)
T- ACUTE LYMPHOBLASTIC LEUKEMIACHANGING INCIDENCE OVER 3 DECADES
33%
25%22%
38%
32%
65%
37%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
MUMBAI DELHI CHENNAI
1980S
1990S
2000S
![Page 35: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/35.jpg)
Frequencies of the major subgroups of Precursor B cell ALL in Indian children
differ from the rest.Siraj AK, et al. Leukemia 2003; 17:1192-93
n= 259 India (%) USA (%) Europe (%)
TEL-AML-1 7 22 23mBCR-ABL* 5 2.2 1.8ELA-PBX1 7 3.8 1.6MLL-AF4 0 1.2 1.6
*Guiterrez MI, et al. J Mol Diagnostics 2005; 7:40-47
![Page 36: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/36.jpg)
• CHENNAI
o DELHI
x MUMBAI
![Page 37: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/37.jpg)
Childhood Acute Lymphoblastic Leukemia Results of MCP-841 in other Centres
Bangalore Trivandrum Jaipur
Total number 127 66 49
CR (%) 96 83 90
TRM(%) 2.4 24.2 16.3
Relapse(%) - 21.8 22.4
CCR(%) 53 57 53
F Up(months) 96 36 38
![Page 38: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/38.jpg)
ALL : FUTURE PLANSCLINICAL
New ALL protocol
Collaboration with INCTR
Salient features
• More Continuous CT
• More Chemo in 1st year
• Both Inj. & oral CT during Maintenance
• Less RT (1260 cGy)
![Page 39: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/39.jpg)
THE PROBLEM
Limited Resources Lack of Appropriate
(Financial and Human Capital) Research
High
Low capacity to treat Poor Access to therapy Mortality Rate
Late Presentation
&
Late Detection
![Page 40: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/40.jpg)
THE SOLUTION
Limited Resources Appropriate
(Financial and Human Capital) Research
Best
Low capacity to treat Rx Pts. ĉ Best Prognosis Value for Money
Low Intensity Rx
![Page 41: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/41.jpg)
Appropriate Rx
SEEDBiology of
Leukemic cells
SOILGenotype
ALLRx
Outcome
PharmacogeneticsPharmakokinetics
NutritionSupportive
care ComplianceDrug quality
![Page 42: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/42.jpg)
What is detection of MRD
It is nothing but detection of the clones of cells resistant to the chemotherapy given.
“Functional Assay”
![Page 43: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/43.jpg)
Appropriate Rx
SEEDBiology of
Leukemic cells
SOILGenotype
ALLRx
Outcome
PharmacogeneticsPharmakokinetics
NutritionSupportive
care ComplianceDrug quality
![Page 44: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/44.jpg)
Estimation of MRD
(1) Flow cytometry : 2-3 laser Flow-cytometer many antibodiestime consuming expensive
(2) RT-PCR: by TCR receptor; Ig gene rearrangements; known translocations. Individual primers.Expertise not available at all centres.
![Page 45: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/45.jpg)
![Page 46: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/46.jpg)
Can there be a simple way to estimate MRD?
![Page 47: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/47.jpg)
Real Time Analysis of Terminal Deoxy Transferase Gene Expression: A convenient marker for Minimal
Residual LeukemiaBu R, Belgaumi A, Timson G, Banavali S, Al Mahir,
Bhatia K, Gutierrez MI.
• TDT expression by all ALL blasts
• Not expressed normally in PB
• Estimation of TDT in PB by Real time PCR
![Page 48: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/48.jpg)
![Page 49: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/49.jpg)
![Page 50: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/50.jpg)
ALL: “Core Biology” LabAssessment Of Components Of Cure In
Developing Countries
Real time reference laboratory system for risk based classification.
• MRD studies : using single parameter, e.g. TDT
• Using PB
• At diagnosis ; At week 4 & 6 (8)
![Page 51: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/51.jpg)
ALL: “Core Biology” LabAssessment Of Components Of Cure In
Developing Countries
• All samples to be sent to a central lab by courier.
• MRD studies based on single parameter, e.g. TDT.
• 5-7 day turnaround time.• Results sent by e-mail.• Remaining sample to be stored for future
studies.
![Page 52: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/52.jpg)
![Page 53: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/53.jpg)
![Page 54: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/54.jpg)
What Is The Best Way To Risk Stratify Children With ALL In
Developing Countries?
One parameter (Not multiple like clinical, IP, DI, Cytogen, Mol, MRD)
MRD EstimationSimplest version using single parameter
Functional assay
![Page 55: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/55.jpg)
Management of Childhood ALL
Common Standard Rem. Ind Protocol
Estimation of MRD at D29/D43
< 0.01 % < 0.1 % > 1 %
? Less intensive Rx? Shorter duration
D. D. I Allo. BMTInvestigational Therapies
![Page 56: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/56.jpg)
Childhood Cancers are
CURABLE
PROVIDED THEY ARE…. diagnosed earlydiagnosed properlytreated appropriately
![Page 57: Childhood Acute Lymphoblastic Leukemia: Risk Stratification in Developing Countries Shripad Banavali MD(Med;Bom), BC(Ped;USA), BE(Hem-Onc;USA) Tata Memorial](https://reader035.vdocuments.site/reader035/viewer/2022070305/5514344e550346dd488b6142/html5/thumbnails/57.jpg)
ALL TEAM
Clinical Lab Studies INCTR Collaboration
Dr. S.D.Banavali Dr.C.N.Nair Dr. Ian MagrathDr. P.A.Kurkure Dr. Ashok Kumar Ms. Melissa AddeDr. B.Arora Mr. Sashikant Dr. Kishore BhatiaDr. S.K.Pai Dr. A.Chougule Dr. Marina GutierrezDr. P.M.Parikh Dr. P.M. Parikh Dr. R.Bhagwat Dr.S. Barbhaya MSW Dept.Dr. A.Vora Dr.S.Kamath Mr.M.A. PatilSister Asha Dr.P. Kadam Amre Ms. Neelima Dalvi
Ms. A. Paes Dr. S.Chiplunkar Data Managers
Radiotherapy Dr.J.Khode Ms. B.KolhatkarDr.M.A.Muckaden Ms.M.Patkar Ms.R.HawaldarDr.S.Lashkar Ms. B.Tambe Dr. N.Nair Mr.R.KadamSurgery Dr. S.GoswamiDr. R.Mistry Dr.N.Merchant