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Guide
Including acute leukemia and malignant lymphoma, allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure patients with hematologic malignancies
.
When there is no suitable related donor, the patient chooses an unrelated donor
.
According to reports by the International Centre for Blood and Marrow Transplantation Research (CIBMTR) and the European Society for Blood and Marrow Transplantation (EBMT), patients who choose unrelated donors are more likely to use peripheral blood stem cells (PBSCs) as a source
of transplantation.
Research background
Multicenter randomized clinical trials from the Blood and Bone Marrow Transplantation Clinical Trials Network (BMTCTN) showed no significant differences in survival, non-relapsed mortality (NRM), and recurrence rates when PBSC and bone marrow (BM) were used as the source of transplantation in patient cohorts with multiple hematologic malignancies, respectively; However, the prognosis between the two sources of transplantation can vary depending on the underlying disease, so the advantages and disadvantages
of PBSC over bone marrow transplantation need to be further understood based on the underlying disease.
Previous studies have shown that PBSCs have a higher
risk of chronic graft-versus-host disease (cGVHD) compared with bone marrow transplantation.
In addition, the severity of post-transplant adverse events can vary greatly depending on the patient's own specific characteristics, such as disease status, conditioning regimen, and HLA type
.
Based on this, the Japanese researchers compared the clinical outcomes of adult patients with acute myeloid leukemia (AML) who received unrelated donor PBSC or BM transplantation, and identified a subgroup
of patients most likely to benefit from PBSC as the source of transplantation.
Research methods
The investigators analyzed adult patients with AML who received unrelated PBSC or BM transplantation from 2011 to 2018 based on Japan's national registry, in which the choice of graft source was not biased
against PBSC.
Included patients were aged 16 years and older; Patients with no survival data or HLA mismatches at three or more loci were excluded
.
The primary endpoint was post-transplant overall survival (OS).
The secondary endpoint was disease-free survival (DFS); cumulative recurrence rate (CIR); NRM； neutrophil and platelet implantation rate; incidence of acute graft-versus-host disease (aGVHD); incidence of cGVHD; Relapse-free survival (GRFS) with GVHD; Rates of viral, bacterial, and fungal infections and infection-related mortality
.
Research results
Baseline characteristics of the patient
The retrospective study included a total of 2962 patients, 221 in the PBSC group and 2741 in
the BM group.
The median age was 53 years (16-69 years) in the PBSC group and 53 years (16-76 years)
in the BM group.
There was no significant difference between the ECOG PS scores at HSCT and cytogenetic risk at initial diagnosis between
the two groups.
Across the cohort, 49.
7% of patients received HSCT at the first complete remission (CR1), with no significant difference between the two groups (P = 0.
248).
HLA-matched donors were selected in 70.
1% of patients in the PBSC group and 56.
1% in the BM group, a significant difference between the two groups (P<0.
001).
In the whole cohort, 75.
1% of patients chose the myeloablative pretreatment regimen, and there was no significant difference between the two groups; However, the proportion of patients receiving systemic radiotherapy (TBI) was statistically significant in the BM group (61.
8 versus 45.
2 percent, P<0.
001).
For the prevention of GVHD, the PBSC group was more likely to receive tacrolimus-based prophylaxis (95.
0 versus 87.
2 percent, P<0.
001) and antithymoglobulin (ATG; 25.
3% vs 9.
3%, P<0.
001).
The median follow-up for survivors in the PBSC and BM groups was 1.
6 and 3.
4 years
, respectively.
The specific patient characteristics are shown in Table 1
.
Table 1 Baseline characteristics of patients
Results of survival analysis and subgroup analysis
The 3-year OS and DFS rates were 57.
5% and 51.
6% in the PBSC group, and 52.
4% and 48.
3% in the BM group (Figure 1A, B).
The results of multivariate analysis showed that the OS rate (risk ratio [HR], 0.
859, P=0.
230) and DFS rate (HR, 0.
868, P=0.
221) in the PBSC group were not inferior to the BM group (Figure 1A, B).
NRM and 3-year CIRs were 17.
9 versus 30.
6 percent and 22.
6 vs 29.
1 percent, respectively, in the PBSC and BM groups (Figure 1C, D).
Multivariate analysis showed that the PBSC group had lower NRM (HR, 0.
731, P=0.
096), but the CIR was comparable between the two groups (HR, 0.
978, P=0.
872) (Figure 1C, D).
In addition, the incidence of cGVHD was significantly higher in the PBSC group (HR, 1.
367, P=0.
016), but NRM was not increased, mainly due to a significantly lower risk of bacterial infection (HR, 0.
618, P=0.
010), which also reflected a faster
implantation rate in the PBSC group.
The results of these survival analyses suggest that unrelated donor PBSC transplantation is safe for adults with AML, and there is a trend towards benefit of
NRM.
Subgroup analysis results suggest that PBSC transplantation confers a clear OS and/or DFS benefit
in patients with a first complete response and no ATG compared with the BM group.
Fig.
1 OS rate (A), DFS rate (B), non-relapse mortality rate (C) and cumulative relapse rate (D) in PBS and BM groups
Conclusion of the study
Overall, PBSC transplantation from unrelated donors is safe for adult patients with AML; Especially in patients with a first complete response, PBSC transplantation has OS and DFS advantages
.
However, further optimization of cGVHD prevention strategies is needed in the future to improve clinical outcomes
in patients receiving PBSC transplants from unrelated donors.
References: Tomoyasu Jo, Yasuyuki Arai, Tadakazu Kondoa, et al.
Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients.
CYTOTHERAPY .
VOLUME 24, ISSUE 10, P1013-1025, OCTOBER 01, 2022.
https://doi.
org/10.
1016/j.
jcyt.
2022.
05.
009.
Reviewed by Quinta
Typesetting: Quinta
Execution: Quinta
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