Do Patients with High Risk or Relapsed Core Binding Factor Acute Myeloid Leukemia Benefit from Salvage Allogeneic Stem Cell Transplantation?

Background: Acute myeloid leukemia (AML) associated with inv(16), t(16;16), or t(8;21), known as core binding factor (CBF) leukemias, are generally considered favorable risk.  However, relapse occurs in 30-40% of patients who achieve first complete remission (CR1).  It is commonly assumed that allogeneic hematopoietic stem cell transplantation (HCT) is the preferred salvage strategy for relapsed disease, but there are few data to support this clinical practice.  To help guide the practicing clinician, we retrospectively evaluated 67 consecutive patients with CBF-AML treated at a single institution from 2000-2013 to evaluate the efficacy of salvage HCT.

Patients and Methods: Of the 67 patients treated, 63 achieved a CR, 3 received supportive care and 1 died of persistent disease.  Five patients received a transplant in CR1 for high-risk features, including c-kit mutation (n=3), therapy-related AML (n=1) and del-7q (n=1).  Thirty-two patients relapsed, with a median time to relapse of 11.6 months (range 4.6-74.1 months), and 22 received salvage HCT in CR2 (n=21) or refractory disease (n=1).  Reasons for not proceeding to salvage HCT included: infection (n=3) or organ toxicity (n=1) precluding additional therapy, patient refusal (n=1) and lost to follow up (n=4).  One patient is undergoing treatment with the goal to proceed to HCT.  This report includes the 27 patients (median age 39 years, range 3-67.5) who underwent HCT; patients received T-cell depleted (TCD) graft (n=17), double unit cord blood (DUCB, n=5), DUCB with TCD-haploidentical donor graft (n=2) or conventional graft (n=3).  Adult donors were HLA-matched related (n=9), HLA-matched unrelated (n=7), HLA-mismatched unrelated (n=4).  Conditioning was myeloablative in 22 patients and reduced intensity conditioning in 6.

Results: All patients except one engrafted. The rate of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 26% (95%CI 11-44%).  The rate of chronic GVHD at 2 years was 8% (95%CI 1-24%).  The cumulative incidence of relapse/progression and non-relapse mortality at 2 years was 8% (95%CI 1-22%) and 12% (95%CI 3-29%), respectively.  As of July 2013, with a median follow-up among survivors of 26 months (range 2-134 months), 22 of 27 HCT recipients were alive; 2 died of relapse, 1 of GVHD and 2 of multiorgan failure. At 2 years, OS for patients receiving a HCT was 80% (95% CI 58-91%) and PFS was 80% (95%CI 58-91%) (Figure 1).

Conclusions: Our data indicate that HCT represents an important salvage therapy associated with extremely favorable outcomes for patients with relapsed CBF AML and for those with high risk features at presentation. Additional studies in larger patient cohorts are needed to determine the optimal transplant strategy for this group of patients.

Figure 1. Overall Survival and Relapse Free Survival