In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993)

Abstract

An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (P ‫؍‬ .01), and the relapse rate was significantly lower (P < .001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high nonrelapse mortality rate in the highrisk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46%) than those randomized to autologous transplantation (37%; P ‫؍‬ .03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for highrisk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group. This study is registered at http:// clinicaltrials.gov as NCT00002514. (Blood.

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

“…Because a high incidence of relapse is the main cause of treatment failure in adults with ALL, the use of allogeneic stem cell transplantation (SCT) as post-remission therapy has become a widely-accepted strategy. In the setting of myeloablative conditioning (MAC), the graft-versusleukemia (GVL) effect for adult ALL has been definitely confirmed from several "donor vs. no donor" comparisons [8][9][10]. However, nonrelapse mortality (NRM) may counterbalance that favorable overall outcome observed after MAC-SCT in patients with advanced age or comorbidities.…”

Allogeneic transplantation is not superior to chemotherapy in most patients over 40 years of age with Philadelphia‐negative acute lymphoblastic leukemia in first remission

“…Several studies addressed this question in the younger patient population using a 'genetic' assignment that allocated patients to HSCT in first remission based on donor availability. The largest of these studies, the MRC UKALL XII/ECOG2993, demonstrated an OS benefit for HSCT in first remission for the Ph-negative cohort but this OS advantage was lost for patients older than 35 years-old or those with elevated WBC counts at diagnosis, mainly due to an increase in NRM with HSCT that reached 36% at 2 years [9]. These findings were later confirmed in an individual-patient-data meta-analysis that pooled results from 13 studies [22].…”

“…Previous reports demonstrate that ALL patients with high risk features (generally defined as older age, high WBC at diagnosis or high risk cytogenetics) do not benefit from transplant as compared to patients without these features, due to a considerable NRM that offsets the lower relapse rate entailed with HSCT [9,22]. Accordingly we defined high-risk in this cohort as WBC count at diagnosis of 30 3 10 9 /L or 100 3 10 9 /L for Bor T-cell ALL, respectively or MLL rearranged leukemia [23].…”

“…1 and 2; P value nonsignificant for both comparisons). The 3-year CIR and NRM were 61% [41-76] and 9% [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] for the chemotherapy-only group and 28% and 32% for the transplant group (Table II; Fig. 3; P 5 0.011 for CIR and P 5 0.014 for NRM).…”

“…The MRC UKALL XII/ECOG2993 trial reported that ALL patients older than 35 years (defined as high risk in that trial) do not benefit from HSCT in first remission when compared with postremission chemotherapy due to the relatively high nonrelapse mortality (NRM) associated with HSCT [9]. In another analysis, HSCT did not seem to entail a survival benefit in 55 transplant-eligible patients 50-70 years old registered on various PETHEMA group trials that were analyzed according to donor availability [10].…”