Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin

Abstract

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25; Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38-100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial

“…25 No cardiac insufficiency occurred, confirming that idarubicin can safely replace daunorubicin. 26,27 The achievement of CR was influenced by age and cytogenetic features. 8,28 Translocation t(9;22) or BCR/ABL rearrangement decreased the CR rate (54%) as reported.…”

Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial

“…Between October 1996 and July 2000, 377 adults with de novo ALL were registered in the GIMEMA ALL 0496 protocol (Figure 1), which was derived from the ALLVR589 regimen 9 and included patients aged 14-60 years with a diagnosis of ALL, with the exclusion of L3 B-ALL. The study was approved by the Institutional Review Board of the Department of Cellular Biotechnologies and Hematology, "La Sapienza" University of Rome.…”

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study

“…Thus, the increased dose intensity of DOX alone did not seem to contribute to the increase of CR rate in adult ALL, although the decreased dose intensity of CY might have offset the effect of increased dose intensity of DOX. Recently, Todeschini et al 15 reported 93% of CR rate using a 3-day administration of daunorubicin (DNR), and 55% 6-year EFS in adult ALL (median age, 34) employing high-dose cytarabine (Ara-C) in post-remission therapy. They used three courses of 3-day DNR (30 mg/m 2 /day) at around 3-week intervals, while we used two courses of 3-day DOX (30 mg/m 2 /day) within 10 days.…”

“…Although OS in the present study is not inferior to hitherto reported large-scale studies, 3,4,6,7 recent studies which include highdose Ara-C and/or high-dose MTX in the post-remission therapy report better OS. [15][16][17] Since April 2000, our National Health Insurance policy has been changed to allow us to use high-dose Ara-C. Therefore, we plan to employ high-dose Ara-C regimens in post-remission therapy in the next JALSG ALL study.…”