Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high‐dose cytarabine‐based induction chemotherapy

Abstract

Purpose Outcomes of patients with acute myeloid leukemia (AML) who are refractory to high-dose Cytarabine (HiDAC)-based induction are dismal. Allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage may be effective and potentially superior to conventional salvage chemotherapy. Methods Eighteen percent (285 of 1597) of AML patients were primary refractory to HiDAC-based regimens at the MD Anderson Cancer Center between 1995 and 2009. AHSCT was the initial salvage in 28 cases. These patients were compared against 149 patients who received salvage chemotherapy, but never received AHSCT. Results Patients receiving salvage chemotherapy were older, had higher bone marrow blasts percentage, and higher incidence of unfavorable cytogenetics (P<0.001). Median time from induction to AHSCT was 76 days. Objective response was achieved in 23 of 28 patients (82%) undergoing AHSCT. The incidence of grade III/IV acute and chronic graft versus-host-disease was 11% and 29%, respectively. Median follow up for living patients is 80 months. Median overall survival (OS) was 15.7 months and 2.9 months for AHSCT and chemotherapy, respectively (P<0.001); the 3-year OS rates were 39% and 2%, respectively. ASHCT as initial salvage therapy was identified as an independent prognostic factor for survival in multivariate analysis (HR = 3.03; P < 0.001). Conclusion Initial salvage therapy with AHSCT in patients with primary HiDAC refractory AML is feasible and may yield superior outcomes to salvage chemotherapy.

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

“…Therefore, a new drug which resensitizes blasts to cytarabine may play a key role in future therapy. 21,22 When BCT-100 was combined with cytarabine, cytotoxicity that is greater than the sum of the 2 individual compounds alone was seen in AML samples (F (1,57) 5 6.405, P , .0001) ( Figure 3C). Analysis of individual patient samples showed that BCT-100 synergized with cytarabine (CI , 1) for almost all samples (Table 2).…”

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

“…222 Benefit may also be derived from allogeneic HCT in the presence of active disease, with CR2 achieved in 42% and long-term survival observed in 9% to 22%. [228][229][230][231] Another approach for patients with refractory or active disease is to use a short course of chemotherapy such as fludarabine, cytarabine, and amsacrine immediately prior to RIC and allogeneic HCT. With this approach, CR rates after allogeneic HCT of 70% to 90% are achieved, with expected 4-year survival ranging between 32% and 45%.…”

Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy

“…In a more recent report from the MD Anderson Cancer Center, Jabbour et al 22 compared outcomes of 28 primary refractory AML patients who underwent an allogeneic HCT as initial salvage to 149 patients with primary refractory AML who received salvage chemotherapy alone. The 28 patients received grafts from: an HLA-matched sibling, n = 18; an HLA-matched unrelated donor, Abbreviations: BU = busulfan; CLO = clofarabine; DFS = disease-free survival; FLAMSA = fludarabine, cytarabine and amsacrine; HCT = hematopoietic cell transplantation; OS = overall survival; RIC = reduced-intensity conditioning.…”