Allograft After Pediatric-Inspired Therapy Does Not Improve Young patient's Outcome with High Risk Philadelphia- Chromosome-Negative Acute Lymphoblastic Leukemia (Ph-ALL). A Single Center Report

Abstract 3528

Allogeneic stem cells transplant (allo-SCT) is currently the preferred therapeutic option for young adults with Ph- ALL in first CR. However, the results of different studies suggested that pediatric-inspired therapy have markedly improved the outcome of these patients. In our monocentric study, we analyzed the impact of the allo-SCT on outcome in adults treated within these pediatric-inspired trials.

Between April 2002 and March 2010, 75 young adult patients with Ph- ALL were treated in our clinical unit. 70 patients (49 men and 21 women) were in complete remission (CR) (93%) after induction chemotherapy (4 after two courses), 2 died before evaluation (3%) and 3 patients were refractory and died with progressive disease (4%). The median age of the population was 33 years (range, 16–59). Among the 70 patients in CR, 54 (77%) were considered at high-risk ALL and therefore eligible for allo-SCT after 1 or 2 consolidation courses. Baseline high-risk factors were: WBC count of ≥ 30 × 10⁹/L for B-lineage ALL, clinical and/or morphologic CNS involvement, t(4;11) and/or MLL-AF4 fusion transcript, t(1;19) and/or E2A-PBX1 fusion transcript and low hypodiploidy and/or near-triploidy. Fourteen patients with low-risk ALL received chemotherapy alone with late intensification followed by maintenance therapy.

With a median follow-up of 36.5 months, median overall survival (OS) for the entire population was not reached and the estimated OS at five years was 75% (70-80%). The high-risk factors as previously defined could separate two different groups with statistically different outcome. In the low-risk (LR) group, none patient died or relapsed during this study. While, in the high-risk (HR) group, 11 of 54 patients (20%) relapsed and 14 patients (26%) died. For the LR group and the HR group, the estimated OS at five years was respectively 100% and 69% (64-74%) (p=0.04) and the estimated disease free survival (DFS) was respectively 100% and 61% (56-66%) (p=0.02).

In the HR group, 30 of the 54 patients (55.5%) had donor and had received allogeneic SCT, 28 of 30 patients after myeloablative conditioning regimen, 12 patients with related donor and 18 patients with unrelated donor. The 24 other patients without donor had received the same chemotherapy than patients in the LR group with late intensification and maintenance therapy. There was no difference between the two subgroups for death: 6 patients with donor (D+) and 8 without donor (D-). Nevertheless, there was more relapses in the subgroup D- (8 relapses) than in the subgroup D+ (3 relapses) (p=0.006). At five years, in the subgroup D+, the estimated OS and DFS were respectively 75 % (68-82) and 72 % (66-78). In the subgroup D-, the estimated OS and DFS were respectively 62 % (55-69) and 48 % (41-55). There was no difference between two subgroups D+ and D- for OS (p=0.4) and DFS (p=0.19). In addition, there was no difference for age, sex, risk factor and initial characteristic of the disease.

These results suggest that allograft might not improve the outcome of patient with high-risk Ph- ALL. One explanation is that pediatric-inspired induction chemotherapy improves the outcome of the whole population (75% of overall survival) and this advantage decreases the impact of the allo-SCT. Nevertheless, allo-SCT decreased the risk of relapse but did not modify OS and DFS. However, more patients are necessary to confirm these results in a multicentric study.