All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.

The AML Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy
  TRANSLATE

The AML Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the AML Hub cannot guarantee the accuracy of translated content. The AML Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact

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

Jun 13, 2022
Share:
Learning objective: After reading this article, learners will be able to cite a new clinical development in AML

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*

Outcome, % (unless otherwise stated)

RIC

MAC

p value

Neutrophil engraftment at Day 60

89.7

94.4

0.08

Median time to engraftment, months

17

16

Incidence of Grade 24 aGvHD at Day 180

30.0

30.3

0.98

Incidence of Grade 34 aGvHD at Day 180

9.3

15.0

2-year cGvHD

26.9

27.5

0.89

Extensive cGvHD

10.9

13.5

0.80

2-year NRM

15.1

22.8

0.48

2-year RI

58.3

51.1

0.24

2-year LFS

26.6

26.0

0.55

OS

31.4

39.7

0.41

GRFS

16.4

12.1

0.88

aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; GRFS, GvHD relapse-free survival; LFS, leukemia-free survival; MAC, myeloablative conditioning; NRM, non-relapse mortality; OS, overall survival; RI, relapse incidence; RIC, reduced intensity conditioning.
*Data from Nagler, et al.1
All p values were two-sided with a type 1 error rate fixed at 0.05.

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 24 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 24 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.

  1. Nagler A, Peczynski C, Dholaria B, et al. Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia. Bone Marrow Transplant. 2022. Online ahead of print. DOI: 1038/s41409-022-01693-8

Share: