scholarly journals HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3969-3978 ◽  
Author(s):  
Cladd E. Stevens ◽  
Carmelita Carrier ◽  
Carol Carpenter ◽  
Dorothy Sung ◽  
Andromachi Scaradavou

AbstractDonor-recipient human leukocyte antigen mismatch level affects the outcome of unrelated cord blood (CB) transplantation. To identify possible “permissive” mismatches, we examined the relationship between direction of human leukocyte antigen mismatch (“vector”) and transplantation outcomes in 1202 recipients of single CB units from the New York Blood Center National Cord Blood Program treated in United States Centers from 1993-2006. Altogether, 98 donor/patient pairs had only unidirectional mismatches: 58 in the graft-versus-host (GVH) direction only (GVH-O) and 40 in the host-versus-graft or rejection direction only (R-O). Engraftment was faster in patients with GVH-O mismatches compared with those with 1 bidirectional mismatch (hazard ratio [HR] = 1.6, P = .003). In addition, patients with hematologic malignancies given GVH-O grafts had lower transplantation-related mortality (HR = 0.5, P = .062), overall mortality (HR = 0.5, P = .019), and treatment failure (HR = 0.5, P = .016), resulting in outcomes similar to those of matched CB grafts. In contrast, R-O mismatches had slower engraftment, higher graft failure, and higher relapse rates (HR = 2.4, P = .010). Based on our findings, CB search algorithms should be modified to identify unidirectional mismatches. We recommend that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible.

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4136-4136
Author(s):  
Eliane Gluckman

The article by Komanduri et al in this issue of Blood describes immune reconstitution after human leukocyte antigen (HLA)-mismatched cord-blood transplantation. As expected, a profound reconstitution deficiency was observed; a study of some subpopulations could be predictive of the outcome.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Li ◽  
Xiaofan Li ◽  
Yiling Chen ◽  
Duihong Li ◽  
Xianling Chen ◽  
...  

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p>0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175–0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p<0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.


Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4318-4327 ◽  
Author(s):  
Joanne Kurtzberg ◽  
Vinod K. Prasad ◽  
Shelly L. Carter ◽  
John E. Wagner ◽  
Lee Ann Baxter-Lowe ◽  
...  

Abstract Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 × 107 TNC/kg (range, 1.5-23.7) with 3.9 × 107 TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm3 and platelets 50 000/μL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.


Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1322-1330 ◽  
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Takaaki Konuma ◽  
Nobuhiro Tsukada ◽  
...  

Abstract We studied the clinical outcomes of 171 adults with hematologic malignancies who received unrelated cord blood transplantation (CBT) as a primary unrelated stem-cell source (n = 100), or bone marrow transplant (BMT) or peripheral blood stem-cell transplant (PBSCT) from related donors (n = 71, 55 BMT and 16 PBSCT). All patients received myeloablative regimens including 12 Gy total body irradiation. We analyzed the hematologic recovery, and risks of graft-versus-host disease (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Significant delays in engraftment occurred after cord blood transplantation; however, overall engraftment rates were almost the same for both grafts. The cumulative incidences of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients were significantly lower than those among BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data suggest that unrelated cord blood could be as safe and effective a stem-cell source as related bone marrow or mobilized peripheral blood for adult patients when it is used as a primary unrelated stem-cell source.


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