Improved outcome in adult B-cell acute lymphoblastic leukemia

Abstract

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studies. The diagnosis of B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg) expression with > 25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65 y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y). The patients received either a conventional (N = 9) ALL treatment regimen (ALL study 01/81) or protocols adapted from childhood B-ALL with six short, intensive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26 were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60 mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (e 2,500/m2) or large tumor burden and was obligatory for all patients in study B-NHL86. Central nervous system (CNS) prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study where all the patients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates increased from 44% to 63% and 74%, the probability of leukemia free survival (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to relapse was different for BM, 92 days, and for isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall CNS relapses changed from 50% to 57% and 17%, most probably attributable to the high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B-NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL, LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adverse impact on the outcome. Elderly B- ALL patients (> 50 years) also benefited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of cyclophosphamide or ifosphamide seem the two major components of treatment.

The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group Karyotype Database in acute lymphoblastic leukaemia: a valuable resource for patient management

“…Patients with these translocations were originally associated with an extremely poor prognosis. They were found to respond well to short-term dose intensive regimens showing a significant increase in overall survival compared to those treated with ALL regimens (139). Thus, urgent cytogenetic or molecular confirmation of these abnormalities is required for optimum patient management.…”

Intensive short‐term chemotherapy regimen induces high remission rate (over 90%) and event‐free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia

“…Fifty years after its description [1] the optimal treatment of adult sporadic Burkitt lymphoma/leukemia (BL) still represents a matter of debate [2]. Standard chemotherapy such as CHOP [3] or adult ALL regimens [4] are clearly inadequate for treating BL, with a long term survival ranging from 0 to 30%. By contrast, the employment of intensive pediatric regimens in adult patients determined better results [5][6][7][8].…”

High‐dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia

“…There was no upper age limit. Patients with mature B‐ALL were excluded and treated according to the Berlin–Frankfurt–Munster (BFM) protocol introduced for B‐cell lymphoma (‘NHL‐BFM 90’, Hoelzer et al , 1996; Reiter et al , 1999). The diagnosis of ALL was based on morphology, histochemical and enzymatic stains, and immunophenotyping.…”