Secondary AML outcomes after haplo-HCT: ALWP of the EBMT study

Secondary acute myeloid leukemia (sAML), developing from prior myelodysplasia, myeloproliferative disorders, bone marrow failure syndrome or after treatment for malignant hematologic (other malignant hematologic diseases) or solid tumors, is frequently associated with poor outcomes. Nowadays, for patients with sAML, allogeneic hematopoietic stem cell transplantation (HCT) seems to be the only curative therapy option. Usually, a HLA-matched donor is the ideal choice for transplantation, but the availability of these donors are deficient in everyday clinical practice.^1,2

To investigate whether unmanipulated haploidentical HCT (haplo-HCT) is a feasible alternative therapy option for this patient population, Zhuoyan Li from Vanderbilt University Medical Center, Nashville, TN, USA, et al. retrospectively analyzed the outcomes of sAML patients undergoing haplo-HCT, collecting data from the Acute Leukemia Working Party of the EBMT registry. Results were published ahead of print in a recent issue of the American Journal of Hematology.

In total, 154 patients (median age at transplantation = 60 years) with sAML receiving haplo-HCT between 2006 and 2016 were included in this analysis. Sixty-nine patients were in first complete remission (CR1) and 85 had active disease at transplantation. 38% of patients received ablative (MAC) and 62% received reduced-intensity conditioning (RIC) regimen. Thirty-five patients received in vivo T-cell depletion (TCD) with ATG, 119 received post-transplantation cyclophosphamide (PTCy), and 12 received both. Median follow-up time was 24 months.

Key findings:

• At day 100, grade II–IV acute graft versus host disease (GvHD) was 26.6%
• 2-year cumulative incidence (CI) of chronic GvHD, extensive GvHD, relapse (RI) and non-relapse mortality (NRM) were 26.0%, 9.0%, 29.8%, and 33.2%, respectively
• 2-year overall survival (OS), leukemia free survival (LFS) and GvHD-free/relapse free survival (GRFS) were 43.3%, 37.1%, and 28.3%, respectively
• There was no significant difference in RI, NRM, LFS, OS, or GRFS for graft source, conditioning intensity, age, and performance status
• Active disease associated with higher RI and inferior LFS, OS, and GRFS in comparison with patients in CR1 at time of haplo-HCT
• Compared to PTCy, ATG significantly associated with worse NRM (HR = 2.36, P < 0.04) LFS (HR = 2.26, P = 0.01), OS (HR = 2.16, P = 0.01), and GRFS (HR = 1.95, P = 0.02)

The authors highlighted that their study had some key limitations including its retrospective registry based nature, missing data, inconsistencies in the conditioning regimen. However, they noted that their study of “haploHCT in a rather large cohort of sAML is of clinical importance”.

In conclusion, this analysis showed that haplo-HCT could be a feasible alternative therapy option for patients with sAML when HLA-matched transplantation is not available. Furthermore, this data demonstrated that ATG is associated with significantly poorer outcomes compared to PTCy, also conditioning doses and stem cell source did not impact outcomes, however, patients transplanted in CR had improved outcomes compared with sAML patients who received haplo-HCT in relapse. Lastly, the authors added that further prospective studies are required in order to support these findings.