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Prognostic Significance of T-Lineage Acute Lymphoblastic Leukemia in Children

Prognostic Significance of T-Lineage Acute Lymphoblastic Leukemia in Children. LS Arya Senior Consultant, Pediatric Oncology Indraprastha Apollo Hospitals, New Delhi Formerly: Prof. of Pediatrics and Head of Pediatric Oncology All India Institute of Medical Sciences, New Delhi.

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Prognostic Significance of T-Lineage Acute Lymphoblastic Leukemia in Children

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  1. Prognostic Significance of T-Lineage Acute Lymphoblastic Leukemia in Children LS Arya Senior Consultant, Pediatric Oncology Indraprastha Apollo Hospitals, New Delhi Formerly: Prof. of Pediatrics and Head of Pediatric Oncology All India Institute of Medical Sciences, New Delhi

  2. Objective • To study the frequency, clinical features and outcome of patients with T-Lineage Acute Lymphoblastic Leukemia (ALL) in comparison with B-Lineage ALL treated with a uniform therapeutic regimen (MCP 841 protocol). • To identify the poor prognostic factors in T-ALL patients

  3. T-Lineage ALL • Distinct biological subtype of ALL comprising about 15% of all pediatric ALL • Frequently associated with unfavourable features at presentation like • Male sex • Age >10 years • WBC count >50,000/mm3 • Mediastinal lymphadenopathy • CNS disease

  4. Acute Lymphoblastic Leukemia (AIIMS, New Delhi) • June 1992 – June 2002 • Total patients – 254 • Immunophenotyping done – 199 (78.3%) • T-Lineage ALL – 60 (30%) • B-Lineage ALL – 139 (70%)

  5. Comparison of clinical features between T and B –Lineage ALL (n=199)

  6. NCI risk group (Age and WBC criteria)

  7. Protocol MCP-841 Cycle Chemotherapy Schedule Induction 1 (I1) Prednisolone 40mg/m2 PO, days 1-28 Vincristine 1.4mg/m2IV, days1,8,15,22,29 L-Asparaginase 6000U/m2 IM, ALT x10, 2-20 Daunorubicin 30mg/m2 IV, days 1,8,15 IT-Methotrexate 12mg* days 1,8,15,22 Induction 2 (I2) Mercaptopurine 75mg/m2PO,days 1-7& 15-21 Cyclophosphamide 750mg/m2 IV, day 1 & 15 IT-Methotrexate 12 mg*, days 1,8,15,22 Cranial Irradiation 180 cGy, x 9 days (1800cGy *1-<2 yrs– 8 mg, 2-<3 yrs – 10mg, >3 yrs – 12mg

  8. Protocol MCP-841 Cycle Chemotherapy Schedule Repeat Induction 1 (I1) Same as Induction 1 as per Induction 1 Consolidation (C) Cyclophosphamide 750mg/m2 IV, day 1 & 15 Vincristine 1.4mg/m2 IV, day 1 & 15 Mercaptopurine 75mg/m2 PO,days 1-7 & 15-21 Cytarabine 70mg/m2 SC, every 12 hrs x 6 doses, days 1-3 & 15-17

  9. Protocol MCP-841 Cycle Chemotherapy Schedule Maintenance (M) (6 Cycles) Vincristine 1.4mg/m2 IV, day 1 Predinisolone 40 mg/m2 PO, days 1-7 Daunorubicin 30 mg/m2 IV, day 1 L- Asparaginase 6000U/m2 IM, days 1,3,5,7 Methotrexate 15mg/m2 PO, once a week for 12 weeks begin on day 15 Mercaptopurine 75mg/m2 PO, daily, 3 weeks out of every four for a total of 12 weeks begin on day 15. Total duration - 2yrs

  10. Survival

  11. Overall Survival B = 68.7 ± 4.7 T = 61.5 ± 7.6 P=0.94

  12. Event Free Survival T=49.9+7.4 .B= 47.1+5.1 P=0.54

  13. NCI Risk Group

  14. Event Free Survival NCI Risk Groups Standard risk B = 55.4 ± 6.4 T = 35.9 ± 12.0 P=0.19 High risk T = 57.9 ± 9.1 B = 35.7 ± 8.1 P=0.005

  15. T-Lineage ALL Univariate Analysis for EFS Prognostic Factor P value • Age 0.90 • Sex 0.36 • WBC Count 0.26 • Lymphadenopathy 0.67 • Mediastinal adenopathy 0.92 • Hepatosplenomegaly 0.12 • CNS disease 0.96

  16. Frequency of T-ALL (Western Studies) • Dana Farber group (DFCI) Silverman et al, Blood 2001 7.4% • UK ALL group Oeden et al, Leukemia 2000 11% • BFM Group Schrappe et al, Leukemia 2000 13%

  17. Frequency of T-ALL (Indian Studies) • TMH, Mumbai (<21 yrs) Advani et al, Ann Oncol 1999 21% • Cancer Institute, Chennai (<15 yrs) Rajalekshmy et al, Leuk Res 1997 46% • Present Study, Delhi (<15 yrs) 30%

  18. Outcome in T and B-Lineage ALL T-Lineage B-Lineage BFM90 Schrappe et al Leukemia 2000 60.2 78.1 DFCI Silverman et al, Blood 2001 79.8 84.0 Pediatric Oncology group Pullen et al, leukemia 1999 50.7 70.4

  19. NCI Risk Group(Based on Age & WBC criteria irrespective of immunopehotype) T-Lineage B-Lineage Children Cancer Group(CCG) Uckun et al, Leuk Lymph 1996 75.2 70.9 Present Study New Delhi 49.9 47.1 TMH Mumbai Advani et al, Ann Oncol 1999 No Difference

  20. Prognostic Significance of T-ALL

  21. T-Lineage ALLConclusion • Even though high risk features were more frequent in T-lineage ALL, their outcome was similar to that of B-lineage patients and none of the prognostic factors were found to have an adverse impact on outcome

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