Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia

Eur J Haematol. 2007 Feb;78(2):102-10. doi: 10.1111/j.1600-0609.2006.00778.x. Epub 2006 Nov 6.

Abstract

Background and aim: Only 20-30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph-) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial.

Patients and methods: From 1996 to 2006, 33 patients > or = 55 yr with Ph- ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year.

Results: Median (range) age was 65 yr (56-77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%-57%) and 46% (22%-70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022-0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05).

Conclusions: The prognosis of elderly Ph- ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Asparaginase / adverse effects
  • Comorbidity
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prognosis
  • Remission Induction
  • Severity of Illness Index
  • Survival Analysis
  • Teniposide / administration & dosage
  • Teniposide / adverse effects
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • Dexamethasone
  • Cyclophosphamide
  • Teniposide
  • Mercaptopurine
  • Asparaginase
  • Prednisone
  • Methotrexate
  • Daunorubicin