Unrelated donor versus matched sibling donor in adults with Acute Myeloid Leukemia in first relapse: an ALWP-EBMT study

Despite some great advancements in Acute Myeloid Leukemia (AML) therapy, there still remains a high rate of relapse; the overall relapse risk is still a staggering 45–50% for patients who have achieved Complete Remission (CR) after salvage chemotherapy. Allogeneic stem cell transplantation is considered the only option which results in cure in this patient group. Consequently, the search for a suitable donor is of crucial importance to improve patient outcomes.

Ruggieri A. et al., in association with the Saint Antoine Hospital in Paris, conducted a retrospective registry analysis of relapsed AML patients receiving Unrelated Donors (UD) compared to Matched Sibling Donor (MSD) transplantations. The results were published in September 2016 in the Journal of Hematology & Oncology.

The published results:

• 1554 patients analyzed in this retrospective study.
• The key results with regards to Relapse Incidence (RI), Non-Relapse Mortality (NRM), Leukemia-Free Survival (LFS) and Overall Survival (OS) are as follows:
  • No difference between the 2 groups in terms of cumulative incidence (CI) or median time for neutrophil engraftment, graft failure percentage (5%), CI of day-100 grade II-III acute GVHD or CI of chronic GVHD at 2 years.
  • Achievement of CR within 100 days after HSCT was higher for UD recipients as compared to MSD group (72% vs 66%, p=0.02)
  • Post-transplant UD recipients compared to the MSD recipients experienced higher 2 years probability of OS (33% vs 26%, p < 0.004), LFS (26% vs 21% [HR = 0.83, p < 0.01]) and lower RI (Relapse Incidence) (57% vs 49% [p < 0.001]), however between the two groups the NRM (non-relapse mortality) rates were similar (23% in MSD vs 24% in UD, p = 0.24). See Figure 1.

Figure 1: A Relapse incidence. b Non-relapse mortality. c Leukemia-free survival. d Overall survival by type of donor

Conclusion

In conclusion, the results of this retrospective analysis have demonstrated some promising results for the use of unrelated donors and may help to increase the rate and availability of donors.

Abstract

Background: Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated.

Methods: We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3–157) months.

Results: Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II–IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)).

Conclusions: Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.