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There is limited evidence supporting the use of haploidentical hematopoietic cell transplantation (HCT) as an alternative to traditional matched sibling donor (MSD) and matched unrelated donor (MUD) allogeneic HCT for acute lymphoblastic leukemia (ALL). The existing retrospective, comparative studies have found no differences in the overall survival (OS) between haploidentical HCT and MSD, MUD, or mismatched MUD (MMUD) HCT, and there is a lack of data to establish a superior donor approach among haploidentical HCT with posttransplant cyclophosphamide (PTCy), 7/8 human leukocyte antigen-matched unrelated donor (7/8 HLA-matched-UD) HCT, and umbilical cord blood (UCB) HCT for adult patients with ALL.1
Wieduwilt and colleagues recently published in Blood Advances, a retrospective study comparing outcomes between adult patients with ALL undergoing haploidentical HCT using PTCy versus MSD HCT, MUD HCT, 7/8-HLA-matched-UD HCT, or UCB HCT.1 Here we summarize the key findings.
This was a retrospective, cohort study using patient data generated from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. Eligible patients were aged >18 years, were in complete remission (CR) 1, 2, or 3+ undergoing their first allogeneic HCT from a haploidentical, HLA-matched sibling, 8/8 HLA-matched unrelated, 7/8 HLA-matched unrelated, or UCB donor.
Secondary outcomes included:
A total of 4,201 patients were included in the five cohorts and the baseline characteristics were well balanced for age, sex, Karnofsky performance status, HCT-comorbidity index (HCT-CI), immunophenotype, cytogenetic risk, Philadelphia chromosome (Ph)/BCR-ABL1 status, disease status, minimal residual disease (MRD) status at transplantation, and recipient cytomegalovirus (CMV) serostatus (Table 1).
There were, however, some notable differences between the cohorts as summarized in Table 1. The haploidentical HCT cohort had the lowest percentage of non-Hispanic white patients, and included patients who were more likely to use reduced intensity conditioning (RIC) and bone marrow as graft source.
Table 1. Baseline characteristics*
CMV, cytomegalovirus; CNI, calcineurin inhibitor; CR, complete remission; F, female; HCT, hematopoietic cell transplant; HLA-matched-UD, human leukocyte antigen-matched unrelated donor; M, male; MAC, myeloablative conditioning; MMF, mycophenolate mofetil; MRD, minimal residual disease; MSD, matched sibling donor; MTX, methotrexate; MUD, matched unrelated donor; NA, not applicable; NMA, non-myeloablative; PTCy, posttransplant cyclophosphamide; RIC, reduced intensity conditioning; TBI, total body irradiation; UCB, umbilical cord blood. |
|||||
Characteristic, % (unless otherwise stated) |
Donor/HCT cohort |
||||
---|---|---|---|---|---|
Haploidentical |
MSD |
MUD |
7/8 HLA-matched-UD |
UCB |
|
Median donor age, range |
35 |
41 |
28 |
31 |
NA‡ |
Race |
|||||
Hispanic white |
22 |
15 |
8 |
18 |
21 |
Non-Hispanic white |
43 |
52 |
74 |
49 |
49 |
Black |
15 |
5 |
3 |
8 |
9 |
Asian |
6 |
7 |
4 |
4 |
7 |
Other/not specified† |
14 |
22 |
10 |
20 |
14 |
Time from diagnosis to HCT (CR1-only) |
|||||
0–5 months |
48 |
65 |
59 |
38 |
44 |
6–11 months |
43 |
30 |
37 |
54 |
48 |
≥12 months |
9 |
6 |
5 |
8 |
8 |
Conditioning regimen |
|||||
MAC, TBI-based |
41 |
60 |
58 |
60 |
71 |
MAC, chemotherapy-based |
16 |
20 |
19 |
22 |
4 |
RIC/NMA |
42 |
19 |
23 |
17 |
25 |
Graft source |
|||||
Bone marrow |
41 |
14 |
19 |
29 |
— |
Peripheral blood |
59 |
86 |
81 |
71 |
— |
GvHD prophylaxis |
|||||
CNI + MTX ± others |
0 |
68 |
71 |
70 |
2 |
CNI + MMF ± others |
0 |
15 |
12 |
8 |
87 |
CNI + others |
0 |
7 |
9 |
6 |
2 |
CNI alone |
0 |
4 |
4 |
2 |
5 |
PTCy + CNI ± MMF |
100 |
5 |
4 |
13 |
<1 |
Other prophylaxis |
0 |
1 |
<1 |
<1 |
3 |
In vivo T-cell depletion |
|||||
Antithymocyte globulin |
1 |
5 |
34 |
50 |
13 |
Alemtuzumab |
0 |
2 |
4 |
3 |
0 |
None |
99 |
93 |
61 |
46 |
87 |
In multivariate analysis, compared to haploidentical HCT:
Table 2. Multivariate analysis for outcomes*
aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; CI, confidence interval; D, donor; F, female; HCT, hematopoietic cell transplantation; HR, hazard ratio; LFS, leukemia-free survival; M, male; MSD, matched sibling donor; MUD, matched unrelated donor; NRM, nonrelapse mortality; OS, overall survival; R, recipient; UCB, umbilical cord blood. |
||||
Outcome |
HR (95% CI), p value† |
|||
---|---|---|---|---|
MSD HCT vs Haploidentical HCT |
MUD HCT vs Haploidentical HCT |
7/8 HLA-matched-UD HCT vs Haploidentical HCT |
UCB HCT vs Haploidentical HCT |
|
OS |
1.13 |
1.17 |
1.38 |
— |
≤18 months |
— |
— |
— |
1.93 |
>18 months |
— |
— |
— |
0.68 |
LFS |
1.03 |
1.03 |
1.21 |
— |
≤18 months |
— |
— |
— |
1.40 |
>18 months |
— |
— |
— |
0.58 |
NRM |
1.06 |
1.42 |
2.13 |
2.08 |
Relapse |
0.99 |
0.83 |
0.81 |
0.83 |
aGvHD |
0.92 |
1.17 |
1.33 |
1.83 |
aGvHD |
1.09 |
1.59 |
1.86 |
1.97 |
cGvHD |
— |
— |
1.72 |
1.13 |
D/R sex match = F/M |
2.59 |
2.91 |
— |
— |
D/R sex match = other |
1.37 |
1.38 |
— |
— |
This retrospective study demonstrated that haploidentical HCT using PTCy could be a preferred alternative donor HCT approach in adult patients with ALL, with superior OS compared with 7/8-HLA-matched-UD and UCB HCT. Although the OS was similar with haploidentical HCT compared to traditional MDS and MUD HCT, the risk of GvHD was reduced in the haploidentical HCT cohort. Further research aiming to prevent relapse, reduce death by infections, and establishing the role of haploidentical HCT using PTCy at different stages of ALL remission with a longer-term follow-up are warranted.
References
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