Outcomes of Myeloablative Hematopoietic Stem Cell Transplantation for Patients with Acute Myelogenous Leukemia with Relapsed or Refractory Disease

Allogeneic hematopoietic stem cell transplant (HSCT) has been shown to be of some benefit for patients with acute myelogenous leukemia (AML) with untreated early relapse. However, outcomes for patients who have morphologic evidence of relapsed leukemia are not well defined. We describe our experience with HSCT for patients with active AML at the time of transplant, to determine prognostic factors for outcome after transplant.

We analyzed recipients of myeloablative HSCT from 1997 to 2009 at our institution with morphologically active AML at the time of transplant. Patients were identified through our transplant database, and disease status was verified through medical record review. Forty patients were included based on the presence of circulating blasts at the time of admission for transplant, and/or a positive bone marrow biopsy (>5% bone marrow blasts) immediately prior to transplant. There were 6 patients coded as “relapsed/refractory” in our database whose disease status at the time of transplant was unable to be confirmed and thus were excluded from analysis.

Baseline patient and transplant characteristics are shown in Table 1. 30% of patients were transplanted for primary induction failure, 22% for first untreated relapse (no treatment between first documented relapse and HSCT), 35% for first refractory relapse (did not attain CR with treatment administered at time of first relapse), and 13% had second or greater refractory relapse. The overall survival for all patients was 82% at 30 days; 55% at 100 days; 28% at one year; and 18% at two years post-HSCT. Of 31 deaths, 71% were attributable to disease, 19% to regimen-related toxicity and infection, and 10% to graft-versus-host-disease (GVHD). Seven patients remain alive at the time of analysis, with 6 patients (15%) alive and free of disease more than 3 years post-HSCT. The median follow-up of the disease-free survivors is 9 years; Table 1 shows characteristics for this subgroup. We identified several patterns of interest. Four disease-free survivors were transplanted in first untreated relapse, yielding 44% (4/9 patients) with first untreated relapse that are long-term disease-free survivors. In addition, while most patients were transplanted with circulating blasts, 5 of 6 disease-free survivors did not have circulating disease. Although 40% of transplants were from unrelated donors, 5 of 6 disease-free survivors received sibling transplants.

Our review of patients with morphologically apparent relapsed or refractory AML confirmed that a subset of patients can achieve a durable remission from HSCT. The majority of these long-term survivors shared important characteristics, including (1) lack of circulating blasts at transplant, (2) sibling donors, and (3) first untreated relapse disease status. This information may serve a prognostic purpose, and may assist in identifying appropriate candidates for transplant or for alternative therapies. However, it was not possible based on our analysis to predict reliably those who would not experience long-term survival. Except for second or greater refractory relapse, there was no factor that identified patients who had no benefit from HSCT. As such, HSCT remains a viable option with the potential for long-term disease-free survival in this population.

No relevant conflicts of interest to declare.