Allogeneic hematopoietic cell transplantation for primary refractory acute lymphoblastic leukemia: A report from the Acute Leukemia Working Party of the EBMT

Abstract

BACKGROUND: Patients with primary refractory acute lymphoblastic leukemia (PREF ALL) who fail to achieve a complete remission (CR) after 2 courses of chemotherapy have a dismal prognosis without undergoing allogeneic hematopoietic cell transplantation (HCT). To the authors’ knowledge, there currently are no data regarding factors influencing transplantation outcomes. METHODS: The authors retrospectively studied outcomes of transplantation for cases of PREF ALL reported to European Society for Blood and Marrow Transplantation registry. Eligibility criteria for the current analysis included adult patients who underwent their first HCT for PREF ALL between 2000 and 2012. PREF disease was defined as the failure to achieve a morphological CR after 2 courses of induction chemotherapy. RESULTS: Data regarding 86 adult patients were analyzed. With a median follow-up of 106 months, the probability of survival was 36% at 2 years and 23% at 5 years. The probability of leukemia-free survival was 28% and 17%, respectively, and the probability of nonrecurrence mortality was 20% and 29%, respectively, at 2 years and 5 years. For 66 patients who achieved a CR (77%), the survival at 2 years and 5 years was 36% and 29%, respectively. In multivariate analysis, use of total body irradiation was found to be associated with improved survival. Total body irradiation and infusion of female hematopoietic cells into male recipients was associated with improved leukemia-free survival. These findings were incorporated into a scoring system that identified 3 groups (those with 2, 1, or no prognostic factors) with survival rates of 57%, 22%, and 8%, respectively. CONCLUSIONS: Although overall these patients would clearly benefit from the introduction of novel antileukemic therapies, the data from the current study support the use of allogeneic HCT in selected patients with PREF ALL

Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia

“…This broad indication for HSCT may have contributed to transplantationrelated mortality; nevertheless, mortality is in line with reports of HSCT in standard of care ranging between 20% to 30%. [31][32][33][34][35] The proportion of patients not undergoing transplantation was small, and the study was neither planned nor powered to assess the impact of HSCT after blinatumomab treatment.…”

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

“…The CR rate achieved with tisagenlecleucel is clearly higher than expected with conventional combination chemotherapy or single-agent use of the recently-approved targeted therapies for this patient population (Table 3). On the basis of registry or single-arm trials, only allogeneic HSCT (9) or combinations of chemotherapy with a targeted agent (10) provide for CR rates comparable to those demonstrated with tisagenlecleucel in CCTL019B2202, but the duration of response after these types of therapies is known to be quite limited (9)(10)(11). The optimal sequencing of therapies for R/R BCP ALL based on safety and efficacy considerations therefore remains to be determined.…”

Chimeric antigen receptor T‐cell therapy as a bridge to haematopoietic stem cell transplantation for refractory/relapsed B‐cell acute lymphoblastic leukemia

“…The complete remission (CR) rate is about 30% with salvage chemotherapy and the survival was 24% at 3 years even when 75% cases underwent allogeneic haematopoietic stem cell transplantation (allo‐HSCT) in the German multicenter study group for relapsed ALL (Fielding et al , ; Gökbuget et al , ). For refractory ALL patients, the 2 years overall survival (OS) and leukaemia‐free survival (LFS) were only 36% and 28%, respectively, with allo‐HSCT reported by Pavlů et al (). In the patients with advanced B‐ALL, chimeric antigen receptor T‐cell (CAR‐T) therapy has shown promising results with a much higher CR rate of approximately 70–90% (Davila et al , ; Lee et al , ; Kenderian et al , ; Liu et al , ).…”