In the subgroup of CD34 cell dose ≤ 0.85 × 105/kg, the anti-HLA antibodies showed a significant impact on neutrophil (P = .0061; B) and platelet recovery (P = .020; D). Positive serum crossmatch as predictor for graft failure in HLA-mismatched allogeneic blood stem cell transplantation. For acute GVHD of grade II-IV, other significant variables were diagnosis of lymphoproliferative disease and CD34+ cell dose ≤ 0.85 × 105/kg. All samples were tested with FlowPRA (One Lambda) for class I (ie, HLA-A/B/C) and class II (ie, HLA-DR/DP/DQ) anti-HLA antibodies. Cumulative incidence of neutrophil and platelet recovery in subgroups of CD34 cell dose. Variables were dichotomized as follows: patient age greater or less than 45 years at transplantation, recipient's sex, sex-mismatched donor-patient pair versus matched sex pair, donor-recipient ABO major mismatch versus others for ABO matching, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with multilineage dysplasia versus leukemia, lymphoproliferative disease (lymphoma or myeloma) versus leukemia, advanced versus standard risk of the disease, 2 loci HLA mismatches versus matched or 1 locus mismatch, CD34+ cell dose ≤ 0.85 × 105/kg versus > 0.85 × 105/kg, cyclosporine-based versus tacrolimus-based GVHD prophylaxis, GVHD prophylaxis including methotrexate (MTX) versus no MTX, and G-CSF usage versus no usage. Of the 89 antibody-positive cases, 69 were defined as ab-positive and 20 as positive-vs-CB. Among 386 CBTs, which were first myeloablative stem cell transplantations for malignancies and used a single unit of cord blood, 89 tested positive. No significant interactions were identified between each variable and anti-HLA antibody positivity. Variables with more than 2 categories were dichotomized for the final multivariate model. Multivariate analysis of anti-HLA antibody and CD34 cell dose. As the test system is highly sensitive, it is possible that the result will show that a patient's antibodies have a wide range of specificity. Among variables used in this analysis, HLA disparity at the antigen level, 2 HLA mismatches versus matched or 1 mismatch, did not have a significant effect on the outcome. HLA-A, -B, and -DR (antigen level) were mismatched in the rejection direction in 88% of the cases.

Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. For relapse, other significant variables were advanced disease status and patient's sex being male. Prospective monitoring for alloimmunization in cord blood transplantation: “virtual crossmatch” can be used to demonstrate donor-directed antibodies. The unadjusted cumulative incidence of platelet recovery at 9 months was also significantly different for the ab-negative, ab-positive and positive-vs-CB groups, at 72%, 60% and 33%, respectively (P = .0036). Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. Anti-HLA antibodies did not have a significant effect on grade II-IV acute GVHD, relapse, or TRM. Blood 2010; 116 (15): 2839–2846. © 2010 by The American Society of Hematology, Copyright ©2020 by American Society of Hematology, https://doi.org/10.1182/blood-2009-10-249219. In this analysis there was an effect shown on neutrophil recovery in the ab-positive group as well as in the positive-vs-CB group. In this study with multivariate analysis, the effect of the antibody on neutrophil recovery was significant for ab-positive cases in the CD34 subgroup of more than the median cell dose. Minoko Takanashi, Yoshiko Atsuta, Koki Fujiwara, Hideki Kodo, Shunro Kai, Hiroyuki Sato, Masatoshi Kohsaki, Hiroshi Azuma, Hidenori Tanaka, Atsuko Ogawa, Kazunori Nakajima, Shunichi Kato; The impact of anti-HLA antibodies on unrelated cord blood transplantations. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734. In this analysis, 23.1% of our samples tested positive for an anti-HLA antibody, which is higher than the 15% reported previously with data from a single CB bank.15  However, in this analysis, 2 of the participating CB banks chose samples with positive results from their own screening tests, and thus excluded some of the clearly negative samples. designed the study, analyzed data, and wrote the paper; Y.A. A proportional hazards model for subdistribution of a competing risk. The proportion of female patients in the anti-HLA antibody-positive group was larger than that in the negative group (75% vs 44%, P < .0001), and this resulted in a difference in the sex-matching proportion. The role of anti-HLA antibodies in graft rejection of organ transplantations has been analyzed extensively.10,11  However, only a few studies have analyzed the significance of anti-HLA antibodies in stem cell transplantations,12-14  in which the recipient's immune system is taken over by the donor's cells and for which a great effort is made to match the recipient and donor HLA types at the allele level.

performed research and analyzed the data; H.K., S. Kai, H.S., M.K., H.A.

ab-negative indicates patient does not have anti-HLA antibody; ab-positive, patient has anti-HLA antibody but the CB does not have the corresponding antigen for the antibody specificity; and positive-vs-CB, patient has anti-HLA antibody and the CB has the corresponding antigen for the antibody specificity. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. In rare instances, a condition called Transfusion-Related Acute Lung Injury (TRALI) can occur. The 2-sided χ2 test was used for categorical variables, and the 2-sided Wilcoxon rank sum test was used for continuous variables. There is a report that describes the high positivity rates obtained by this test method as being due to natural antibodies,22  and others regard this test system as too sensitive and lacking clinical relevance.23  The discrepancy in positivity rates between laboratories (data not shown) led us to collect the samples in 1 laboratory for this analysis. Anti-HLA Antibodies: Antibodies against HLA antigens may form after an organ transplant, a blood transfusion or a pregnancy. donating platelets, allowing us the opportunity to perform HLA testing from your donation. Successful engraftment following HLA-mismatched cord blood transplantation for patients with anti-HLA Abs.

Preformed antibody, not primed T cells, is the initial and major barrier to bone marrow engraftment in allosensitized recipients. Ottinger et al showed that the OS for their crossmatch positive cases was significantly lower than that for the crossmatch negative control group among those receiving a transplant at an early stage of the disease,13  and also showed that graft failure is the dominant factor for low OS. For transplant-related mortality, other significant variables were patient age more than 45 years at transplantation, GVHD prophylaxis without MTX and cyclosporin-based GVHD prophylaxis compared with tacrolimus-based GVHD prophylaxis. We thank all of the physicians and staff at the hospitals in Japan who collaborated in this study. In our study, patients with antibodies against the graft (positive-vs-CB) had a significantly higher graft failure rate, an approximately 4-fold increase, and had inferior OS and EFS compared with antibody-negative patients. Application of bead array technology to simultaneous detection of human leucocyte antigen and human platelet antigen antibodies. There are already reports on successful engraftments after CBT by avoiding the corresponding antigens.28,29  The quality of the CB unit also has to be considered, as cell dose is a significant factor for engraftment.25,26  From the multivariate analysis shown in Table 3, it appears that the choice of a unit with an antigen(s) corresponding to the antibody specificity presents a higher risk of graft failure. The impact of HLA antibodies on engraftment of unrelated cord blood transplants. For treatment failure (as a reverse of event-free survival), other significant variables were advanced disease status, patient age more than 45 years at transplantation, diagnosis of lymphoproliferative disease and GVHD prophylaxis without MTX. HLA antibodies have been associated with a potentially serious transfusion reaction known as TRALI (transfusion related acute lung injury). Correspondence: Minoko Takanashi, MD, PhD, Japanese Red Cross Tokyo Blood Center, 2-1-67 Tatsumi, Koto-ku, Tokyo 135-8639, Japan; e-mail: mi-takanashi@tokyo.bc.jrc.or.jp. Disease status at transplantation was categorized as standard risk for the first complete remission or the second complete remission of AML, the first complete remission of acute lymphoblastic leukemia (ALL), the first chronic phase of chronic myeloid leukemia (CML), refractory anemia of MDS or the first complete remission of lymphoproliferative disorders. With multivariate analysis, the ab-positive showed significantly lower neutrophil recovery than the ab-negative (relative risk [RR] = 0.69, 95% CI, 0.49-0.96, p = .027). For the Kaplan-Meier estimate of event-free survival (EFS; C), the impact of anti-HLA antibodies was significant (P = .0001), with EFS at 2 years for the ab-negative, ab-positive and positive-vs-CB groups being 43% (95% CI, 37%-49%), 29% (95% CI, 17%-41%), and 15% (95% CI, 4%-33%), respectively. ab-negative indicates patient does not have anti-HLA antibody; ab-positive, patient has anti-HLA antibody but the CB does not have the corresponding antigen for the antibody specificity; and positive-vs-CB, patient has anti-HLA antibody and the CB has the corresponding antigen for the antibody specificity. In addition, there is a report that shows that priming to 1 alloantigen results in the elimination of donor bone marrow of a different alloantigen.24. Standard risk: 1st and 2nd complete remission of AML, 1st complete remission of ALL, 1st chronic phase of CML, refractory anemia of MDS, 1st complete remission of lymphoproliferative diseases. Search for other works by this author on: Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. The longer survival period under a highly immunosuppressed condition, provided by the second transplantation or autologous recovery, may have contributed to elevate the risk of relapse, which affected the OS. Among the 69 ab-positive cases, 45 had an antibody against an HLA class I antigen, 10 against an HLA class II, and 14 against both a class I and a class II. Samples of 20 μL were incubated with HLA class I–coated and HLA class II–coated microspheres, respectively, for 30 minutes in the dark under gentle agitation. We have clearly shown that the patients' pretransplantation anti-HLA antibodies are a negative factor for engraftment, especially when the specificity corresponds to the donor antigens. CI indicates confidence interval; ab-negative, patient does not have anti-HLA antibody; ab-positive, patient has anti-HLA antibody but the CB does not have the corresponding antigen for the antibody specificity; and positive-vs-CB, patient has anti-HLA antibody and the CB has the corresponding antigen for the antibody specificity. and A.O. Screening for WBC antibodies by lymphocyte indirect immunofluorescence flow cytometry: superior to cytotoxicity and ELISA? The majority of cord blood transplantations (CBTs) have human leukocyte antigen (HLA) disparities. Different forms of the HLA antibody are involved in autoimmune diseases. Neutrophil recovery was also significantly better for the ab-positive group than the positive-vs-CB group (HR = 0.31, 95% CI, 0.12-0.80, P = .015). This is different from our preliminary report, in which the neutrophil recovery of the ab-positive group was similar to that of the ab-negative group.15  This discrepancy might be due to limiting the subjects to recipients of myeloablative conditioning, and to the increase in the number of subjects for analyses containing a higher proportion of alloimmunized cases, together with the difference between the cumulative incidence statistical method used in this study, which considers competing risks, and the Kaplan-Meier method that was used in the previous study. performed statistical analysis and co-wrote the paper; K.F., H.T.

This work was supported in part by a Research Grant for Tissue Engineering (H17-014) and a Research Grant for Allergic Disease and Immunology (H20-015) from the Japanese Ministry of Health, Labor and Welfare.

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