Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor

Deteix, Clémence; Mesnil, Florence; Fürst, Sabine; Milpied, Noël; Yakoub‐Agha, Ibrahim; Fégueux, Nathalie; Latour, Régis Peffault de; Mohty, Mohamad; Chevallier, Patrice; Wallet, Hélène Labussière; Huynh, Anne; Larosa, Fabrice; Bourhis, Jean‐Henri; Cahn, Jean‐Yves; Chantepie, Sylvain; Bay, Jacques‐Olivier; Audat, F.; Foote, Alison; Faucher, Catherine; Marry, Évelyne; Garban, Frédéric; Cellulaire, Société de Greffe de Moelle et de Thérapie Francophone

doi:10.1038/s41409-019-0722-y

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…Many centers have adopted the original Hopkins haplo-BM PTCy protocol for MMUD allo-HCT. The retrospective studies of MMUD allo-HCT in the setting of PTCy showed a lower risk of GVHD and NRM compared to historical ATG or alemtuzumab-based MMUD allo-HCT [18,22,[32][33][34]. Compared to ATG or alemtuzumab, PTCy is associated with better immune reconstitution and hence lower risk of infection-related NRM [35].…”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

et al. 2021

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Background Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. Methods Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. Results The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis. Conclusions CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.

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Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

et al. 2021

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“…For patients with hematologic malignancies requiring allo-HSCT but who lack an MRD, the best choice of alternative stem cell source remains unclear. The different types of alternative donors have disparate advantages and drawbacks in terms of rapidity of obtaining stem cells, efficacy, and tolerability, and the criteria or algorithm for selecting one type of alternative donor over another are not well established 27 . In general, comparing Haplo-SCT and UCBT outcome in the absence of randomized prospective studies is difficult.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 37 articles underwent full-length review; 23 of them were excluded because they only evaluated patients receiving either Haplo-SCT, UCBT, or combined Haplo-SCT and UCBT, nonhematologic cancers, and lack of direct comparison results; 2 articles were excluded due to insufficient data. The final analysis included 12 studies including 2 prospective clinical studies 25,26 and 10 retrospective cohort studies [27][28][29][30][31][32][33][34][35][36] . This included 2,793 patients who underwent Haplo-SCT (1,432 patients) or UCBT (1,361 patients).…”

Section: General Description Of Included Studiesmentioning

confidence: 99%

Haploidentical Hematopoietic Stem Cell Transplantation Versus Umbilical Cord Blood Transplantation in Hematologic Malignancies: A Systematic Review and Meta-Analysis

2020

Cell Transplant

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Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and umbilical cord blood transplantation (UCBT) are two important alternatives when a matched sibling donor is unavailable. Several studies have reported inconsistent clinical outcomes comparing Haplo-SCT and UCBT. Therefore, it is necessary to synthesize the existing evidence regarding outcomes of stem cell transplantations comparing Haplo-SCT with UCBT. We searched article titles that compared transplantation with Haplo-SCT and UCBT in MEDLINE (PubMed), Cochrane library, and EMBASE database. To compare clinical outcomes between Haplo-SCT and UCBT, we performed a meta-analysis of 12 studies and reported the pooled odds ratios (ORs) of 6 end points including overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), relapse rate (RR), acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD). We found that Haplo-SCT was associated with a significantly superior OS (pooled OR of 0.74, 95% confidence interval [CI] 0.68 to 0.80) and PFS (0.77, 95% CI 0.72 to 0.83), as well as a lower NRM (0.72, 95% CI 0.64 to 0.80) and aGVHD (0.87, 95% CI 0.77 to 0.98) compared to the UCBT group. We also found a significantly increased risk of cGVHD in Haplo-SCT group (1.40, 95% CI 1.22 to 1.62). In terms of RR, Haplo-SCT was comparable to UCBT (0.91, 95% CI 0.79 to 1.05). Results of this meta-analysis demonstrate that Haplo-SCT results in better clinical outcomes compared to UCBT in terms of OS, PFS, TRM, and aGVHD, but is inferior to UCBT in terms of increased cGVHD risk. Further prospective comparisons between Haplo-SCT and UCBT are needed.

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“…However, those alternatives are not available in all transplant centers, and there are situations that do not admit the waiting time to identify an alternative donor, such as advanced leukemias or GF. In fact, it has been largely known that in these situations there is a negative impact on survival if the transplant is delayed ( 28 ). Thus, a strategy for monitoring and desensitization should be applied in those situations in which haplo-HSCT with DSAs is the best option.…”

Section: Discussionmentioning

confidence: 99%

Management of Donor-Specific Antibodies in Haploidentical Transplant: Multicenter Experience From the Madrid Group of Hematopoietic Transplant

et al. 2021

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BackgroundDonor specific antibodies (DSAs) can be responsible for graft failure (GF) in the setting of mismatched hematopoietic stem cell transplantation (HSCT). The aim of our study is to report the experience of the Madrid Group of Hematopoietic Transplant (GMTH) in patients with DSAs undergoing haplo-HSCT.MethodsPatients undergoing haplo-HSCT in centers from the GMTH from 2012 to 2020 were included in the study. DSAs were analyzed with a solid-phase single-antigen immunoassay; monitoring was performed during desensitization on days -14, -7, 0 and in a weekly basis until neutrophil engraftment. Desensitization strategies varied depending on center experience, immunofluorescence intensity, complement fixation and type of antibodies.ResultsWe identified a total of 20 haplo-HSCT in 19 patients performed with DSAs in 5 centers. 10 (53%) patients presented anti-HLA class I DSAs (6 of them with > 5000 mean fluorescence intensity (MFI)), 4 (21%) presented anti-HLA class II (1 with > 5000 MFI) and 5 (26%) presented both anti-HLA class I and II (5 with > 5000 MFI). 90% of patients received at least two treatments as desensitization strategy and all experienced a decrease of MFI after desensitization (mean reduction 74%). Only one patient who developed progressive increase of MFI after infusion developed GF. Desensitization treatments used included rituximab, immunoglobulins, therapeutic plasma exchange, incompatible platelets, buffy coat and immunosuppressors. Seventeen (90%) patients achieved neutrophil engraftment; one patient died before engraftment because of infection and one patient with class I DSAs developed primary GF despite an intensive desensitization. After a median follow-up of 10 months, OS and EFS were 60% and 58%, respectively, cumulative incidence of relapse was 5% and NRM was 32%.ConclusionsDespite the optimal strategy of DSAs desensitization remains unclear, the use of desensitization treatment guided by DSAs intensity kinetics constitute an effective approach with high rates of engraftment for patients with DSAs in need for an haplo-HSCT lacking an alternative suitable donor.

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Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor

Cited by 6 publications

References 29 publications

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Haploidentical Hematopoietic Stem Cell Transplantation Versus Umbilical Cord Blood Transplantation in Hematologic Malignancies: A Systematic Review and Meta-Analysis

Management of Donor-Specific Antibodies in Haploidentical Transplant: Multicenter Experience From the Madrid Group of Hematopoietic Transplant

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