AL-10. Outcomes of haploidentical, matched and mismatched unrelated transplantations with posttransplant cyclophosphamide in first complete remission of acute myeloid leukemia

Summary

Posttransplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cells transplantations (allo-HSCT) from haploidentical donor (HID) made it possible to achieve results comparable to matched (MUD) and mismatched (MMUD) transplantations with conventional graft-versus-host disease (GvHD) prophylaxis in first complete remission (CR1) of acute myeloid leukemia (AML), which was confirmed by a substantial number of studies. However, data comparing these three donor groups in the context of the uniform PTCy prophylaxis are limited. Our study aimed to compare the results of haploidentical, MUD and MMUD transplantations all performed with the PTCy prophylaxis.

Patients and methods

A total of 233 adult AML patients in CR1 who underwent allo-HSCT from a haploidentical (n=56), 10/10 (n=117) and 9/10 (n=60) unrelated donors with PTCy GvHD prophylaxis at RM Gorbacheva Research Institute between 2013-2022 years were included. Baseline demographic and clinical characteristics are summarized in Table 1. Two-year overall, leukemia-free and GvHD-relapse-free survival (OS, LFS, GRFS) were analyzed using the Kaplan-Meier method and log-rank test, followed by univariate and multivariate analyses using a Cox regression model. Engraftment, relapse incidence (RI), non-relapse mortality (NRM), acute and chro-nic GvHD were estimated using cumulative incidence (CI) functions, with death as a competing event. CI were evaluated with the Gray test. Statistical analyses were conducted using R version 4.0.1.

Results

Median follow-up time for alive patients was 40.9 (4.2-105.4) months. The engraftment CI was lower in patients receiving haploidentical grafts – 75% (95%CI:61.2-84.5) compared to MUD – 98.1% (95%CI:91.7-99.2) and MMUD – 91.7% (95%CI:80.3-96.6) (p<0.001, p=0.016). The MMUD group had higher rates of aGvHD2-4 – 36.7% (95%CI:24.6-28.8) compared to MUD – 12% (95%CI:6.9-18.6) and HID – 12.5% (95%CI:5.4-22.6%) groups (p<0.001, p=0.003). The same pattern was observed for aGvHD3-4: MMUD – 36.7% (95%CI:24.6-28.8), MUD – 12% (95%CI:6.9-18.6), HID – 12.5% (95%CI:5.4-22.6%) (p<0.001, p=0.003). The MMUD group had a higher cGvHD2-3 rate – 36% (95%CI:23-49%) compared to MUD – 16% (95%CI:10-24). There was a trend towards an increase in NRM in the HID group – 21% (95%CI:11-33) compared to MUD – 10% (95%CI:5.7-17) (p=0.052), with no difference to MMUD – 15% (95%CI:7.5-26) (p=0.5). No difference was observed in RI among the three groups. The univariate analysis showed a decrease of OS in the HID group – 69.7% (95%CI:57.7-84.1), compared to MUD – 83.5% (95%CI:77-90.6) with no difference to MMUD – 76.5% (95%CI:65.8-88.8) (p=0.047, p=0.474). LFS followed a similar manner: 63.8% (95%CI:51.4-79.3), 80.1% (95%CI:73.1-87.7) and 74.7% (95%CI:63.9-87.4), respectively (p=0.025, p=0.255). The MUD group demonstrated higher GRFS – 68.8% (95%CI:60.8-77.8) as to the MMUD group – 45.2% (95%CI:33.4-61.2) (p=0.006), with a statistical tendency of GRFS decrease in the HID group – 54.6% (95%CI:42.2-70.7) (p=0.071). According to the multivariate analysis, higher age (HR=1.06; 95%CI:1.03-1.08; p<0.001), adverse cytogenetic risk (HR=2.03; 95%CI:1.03-3.97; p=0.039), and bone marrow graft source (HR=2.69; 95%CI:1.13-6.4; p=0.025) correlated with lower OS. Higher age (HR=1.04; 95%CI:1.02-1.06; p<0.001), primary refractory AML (HR=1.99; 95%CI:1.09-3.63; p=0.026), and adverse cytogenetic risk (HR=1.87; 95%CI:1.01-3.48; p=0.046) affected LFS. Higher age (HR=1.03; 95%CI:1.01-1.05; p<0.001) and MMUD (HR=1.65; 95%CI:1.01-2.7; p=0.045) was associated with GRFS.

Conclusion

In the absence of an HLA-compatible sibling, MUD remains the primary option for AML patients in CR1, when performing allo-HSCT with PTCy. MMUD demonstrated higher CI of severe GVHD forms, HID – lower CI of engraftment and a statistical trend of increased NRM. Nevertheless, the multivariate analysis of OS and LFS showed adverse cytogenetic risk, primary refractory AML bone marrow as a graft source to have a stronger negative prognostic effect, than the donor type.

Keywords

Acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, posttransplant cyclophosphamide, haploidentical donor.