Outcomes of second allogeneic hematopoietic cell transplantation for patients with secondary AML treated with varying conditioning intensities

Secondary acute myeloid leukemia (sAML) often represents a poorer prognosis due to previous treatments, older patient age, and the number of high-risk cytogenetic abnormalities.¹ Second hematopoietic cell transplantation (HCT2) offers a potential curative option after relapse following a previous transplantation; however, there are limited data available on factors impacting clinical outcomes.¹

Arnon Nagler and colleagues¹ performed a registry-based, multicenter study aiming to assess the impact of conditioning intensity on HCT2 outcomes by comparing relapse rate and transplant outcome among patients who underwent either reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC).

Study design

A total of 215 patients were included in the study; 134 (62.3%) were treated with RIC and 81 (37.7%) with MAC. The eligibility criteria were patients aged ≥18 years, with sAML in complete remission or active disease, and who underwent a HCT2 between 2005 and 2019. Exclusion criteria included receiving umbilical cord blood or T cell-depleted haploidentical transplants in HCT2, an unknown status or date of relapse, or an unknown conditioning intensity.

Results

The median duration of follow-up from HCT2 for patients on RIC and MAC was 41.1 months and 28.5 months, respectively. In both cohorts, the median year that patients underwent HCT2 was 2014. The median relapse time for HCT1 was 15 months in the RIC cohort and 12.6 months in the MAC cohort (p = 0.55). The median time between HCT1 and HCT2 was 23.9 months in the RIC cohort and 18.8 months in the MAC cohort (p = 0.65). However, the median time for relapse after HCT2 was comparable between the cohorts; 55.1 months for RIC and 52.5 months for MAC. Disease status did not significantly differ between the RIC and MAC cohorts; complete remission was 40.3% and 40.8%, respectively (p = 0.95). A total of 38 patients received MAC for both HCT1 and HCT2, at a median interval of 604 days.

Transplant outcomes

The results of the univariate analysis are shown in Table 1.

Table 1. Univariate analysis of both patient cohorts*

Multivariate analysis revealed relapse incidence was significantly lower in the MAC cohort (p = 0.006) and leukemia-free survival (LFS) was significantly higher compared with the RIC cohort (p = 0.042). Overall survival, graft-versus-host disease (GvHD) relapse-free survival, and non-relapse mortality (NRM) did not differ significantly between the two cohorts according to the multivariate analysis (p = 0.18, p = 0.6, and p = 0.74, respectively). Moreover, the risk of Grade 2–4 acute and chronic GvHD was similar across the two cohorts.

A Karnofsky performance score <90 was a significant prognostic factor for higher risk of NRM, as were lower overall survival, LFS, and GvHD relapse-free survival. An older age was also a significant factor for higher risk of NRM. Furthermore, achieving complete remission before HCT2 and use of in vivo T-cell depletion were significant prognostic factors for lower Grade 2–4 acute GvHD in the multivariate analysis.

Cause of death

A total of 142 patients died; 92 in the RIC cohort and 50 in the MAC cohort. The most common cause of death was original disease, at 58.4% and 40.8% in the RIC and MAC cohorts, respectively; followed by infection (10.1% and 10.2%, respectively) and GvHD (6.7% and 4.1%, respectively).

Conclusion

The study shows that HCT2 is a feasible option leading to a favorable outcome in ~25% of patients. The use of MAC lowered the incidence of relapse without a significant increase in NRM. Although LFS was significantly higher with MAC versus RIC, overall survival and incidence of GvHD were comparable. Further studies are needed to identify preemptive and prophylactic therapies to further reduce the risk of relapse.