Risk-oriented postremission strategies in adult acute lymphoblastic leukemia: prospective confirmation of anthracycline activity in standard-risk class and role of hematopoietic stem cell transplants in high-risk groups

Abstract

Introduction: Although definite risk classes are well known, risk-adapted modulation of first-line therapy is seldom attempted in adult ALL. So, a prospective validation of the therapeutic efficacy of a protocol (or a component thereof) in specific risk groups is uncommon.

Materials and methods: From 1996-1999 a risk-oriented program (08/96) was evaluated in 102/121 unselected patients (median age 35 years, blast count 0-450 x 10(9)/l, 100 B(lin) (lineage), 21 T(lin)) responsive to induction therapy. The standard risk (SR) class was B(lin) CD10+ Ph- with blasts < 10 x 10(9)/l (prior studies: disease-free survival (DFS) rate 52% at five years with dose-intensive anthracycline-containing programs). The SR protocol was therefore anthracycline-rich (early consolidation cycles with total idarubicin 96 mg/m2), and comprised long-term maintenance. High-risk (HR) patients were eligible to the following three options: allogeneic hematopoietic stem cell transplantation (HSCT) from related family donor; short sequence with high-dose cyclophosphamide-cytarabine-methotrexate followed by melphalan/total body irradiation with autologous HSCT; or T(lin) ALL chemotherapy regimen inclusive of high-dose cytarabine and methotrexate.

Results: Treatment realization and three-year DFS rates according to risk class, HR subset and postremission treatment intensity were the following. SR group (n = 28): realization rate 93%, DFS 68.5%. HR group (n = 74): realization rate 80%, DFS 39% (P = 0.052 vs SR category). In HR group, three-year DFS rates by disease subtype were the following. B(lin) Ph- (n = 35) 43%; Ph+ (n = 19) 13% at 2.7 years (P = 0.006 vs other HR subtypes); T(lin) (n = 18) 59.5%. And DFS rates by treatment intensity were: allograft (n = 21) 40%; autograft (n = 28) 27%; shift to SR protocol (n = 13) 52% (P = ns vs allograft/autograft); T(lin) program (n = 10) 57%. Matched analyses of treatment protocols and disease subtypes suggested a possible therapeutic role of the autograft regimen in B(lin) Ph- ALL with a blast count < 25 x 10(9)/l, and of T(lin) protocol for T(lin) ALL. Comparisons with retrospective control cohorts were confirmatory of anthracycline activity in SR subclass.

Conclusion: The intended strategy was applicable to the majority of study patients, confirming the value of anthracyclines in SR class and, preliminarily, the usefulness a T(lin)-specific treatment. Apart from the case of Ph+ ALL, the indications for high-dose procedures with HSCT remains largely undetermined in this study.