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1.
Prognostic impact of HLA supertype mismatch in single-unit cord blood transplantation
Sugio, T., Uchida, N., Miyawaki, K., Ohno, Y., Eto, T., Mori, Y., Yoshimoto, G., Kikushige, Y., Kunisaki, Y., Mizuno, S., et al
Bone marrow transplantation. 2024
Abstract
The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT.
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Interleukin-10 GCC/GCC haplotype is associated high risk of acute GVHD in patients undergoing allogeneic HSCT in the southern of Brazil
Farias, M. G., Dos Santos, C. A., Paz, A. A., Daudt, L. E.
Transplant immunology. 2024;:102002
Abstract
INTRODUCTION Hematopoietic Stem Cell Transplant (HSCT) is currently an important curative treatment for many patients with malignant and non-malignant diseases. Graft versus host disease (GVHD) represents a major complication in allogeneic HSCT recipients. Several polymorphisms in cytokine genes have recently been investigated as candidates for risk factors for acute-GVHD (aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVE In this study, we analyzed specific interleukin (IL)-10 haplotypes polymorphisms, in a cohort of 99 patients and their respective allo-HSCT donors for aGVHD and risk. RESULTS An association was found between IL-10 promoter haplotype polymorphisms at positions -1082, -819 and - 592 with the occurrence of aGVHD. Patients who have the GCC/GCC haplotype are at increased risk of aGVHD (P = 0.017, HR: 5.42 (95% CI: 1.34-21.84). In the donors group and severity of aGVHD as not found statistical significancy. CONCLUSION The results obtained show the IL-10 GCC/GCC haplotype can be an important biomarker to identify the greatest risk of aGVHD in the patient undergoing HSCT.
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Donor NKG2D rs1049174 polymorphism predicts hematopoietic recovery and event-free survival after single-unit cord blood transplantation in adults
Konuma, T., Hamatani-Asakura, M., Monna-Oiwa, M., Kato, S., Isobe, M., Yokoyama, K., Nannya, Y., Takahashi, S.
Bone marrow transplantation. 2024
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4.
The incidence and role of recipient-specific antibodies (RSA) in allogeneic hematopoietic cell transplantation from mismatched related donors
Sadowska-Klasa, A., Dukat-Mazurek, A., Zielińska, H., Dębska-Zielkowska, J., Piekarska, A., Moszkowska, G., Mensah-Glanowska, P., Zaucha, J. M.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND High titer of donor-specific antibodies (DSA) increases the risk of graft rejection after mismatched related hematopoietic cell transplantation (HCT). There is no data regarding the incidence of anti-HLA recipient-specific antibodies (RSA) and their role after transplantation. OBJECTIVE To identify the incidence of RSA in a mismatched related hematopoietic cell donor population and their possible impact on immune-mediated complications such as acute graft-versus-host (aGvHD) disease and complications resulting from endothelial injury such as transplant-associated thrombotic microangiopathy (TA-TMA) and veno-occlusive disease (VOD). STUDY DESIGN We prospectively analyzed the incidence of anti-HLA antibodies in 28 mismatched related pairs of recipients and their donors transplanted in our center between 2020 and 2022. In positive samples screened for anti-HLA class I and/or II antibodies, identification of the specificity of the HLA antibodies was performed. All recipients suffered from hematological malignancies and received a myeloablative conditioning regimen and immunosuppression consisting of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients were tested for TA-TMA and GvHD development during routine post-transplant visits up to 100 days post-transplant. We used modified Jodele criteria for TA-TMA diagnosis, and GvHD grading was done based on MAGIC criteria. VOD was assessed using the EBMT revised criteria. RESULTS Anti-HLA antibodies were detected in 12 (43%) donors and 9 (32%) recipients. No significant differences between donors and recipients according to age (median 42 [17-69] vs 39 [18-68]), gender, and pregnancy history were observed. No transfusion history was noted in the donor group (p<0.05). RSA antibodies were present more often than DSAs and were detected in 9 out of 12 (75%) anti-HLA positive donors and only 2 out of 9 (22%) recipients, respectively (p<0.05). During the follow-up, 11 patients (39%) developed acute GvHD, grades I-II and III-IV in 9 (32%) and 2 (7%) cases, respectively. Twelve (43%) patients met TA-TMA criteria, and only 1 (3.5%) patient was diagnosed with VOD by day 100 post-HCT. RSA were detected significantly more often in the TA-TMA group: among 12 cases that met TA-TMA diagnosis, in 7 (58%) RSA were present (p<0.05). We did not find a correlation between RSAs and acute GvHD. Patient with VOD did not have RSA-positive donor. There was no difference in membrane attack complex (MAC) concentration in the RSA(+) group on day 30 and 60 post HCT, however, there was a trend toward higher MAC concentration in the RSA(+) group on day 100 - 912 ng/ml (788-1120) vs 616 ng/ml (352-1244) p=0.055. Patients with RSA suffered more often from platelet and red blood cell decrease or transfusion refractoriness, and increased lactate dehydrogenase activity was observed in all RSA (+) cases. CONCLUSIONS Donor`s immune status and the presence of RSA may be associated with higher rates of TA-TMA in mismatched HCT recipients. Antibody-mediated complement activation might be an additional factor influencing TA-TMA occurrence.
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5.
The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan
Borhany, M., Ali, M. S., Ghias, Z., Abid, M., Zafar, S., Shamsi, T.
Cureus. 2023;15(9):e45442
Abstract
Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.
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6.
Impact of donor age and relationship on outcomes of peripheral blood haploidentical hematopoietic cell transplantation
Pruitt, A., Gao, F., De Togni, E., Cochran, H., Godbole, S., Slade, M., Abboud, R.
Bone marrow transplantation. 2023
Abstract
Here we describe a retrospective analysis of outcomes in 299 patients who underwent peripheral blood haplo-HCT with PTCy from July 2009 through May 2021 and their association with donor characteristics. Patients had mostly acute leukemias and high or very high DRI. Multivariate analyses were conducted examining OS, NRM, relapse, cytokine release syndrome, acute and chronic GVHD. Donor characteristics included age, sex, relationship, ABO status, CMV status, and HLA match grade. Our analysis revealed increasing donor age was associated with higher NRM (compared to age <30; age 30-44 HR, 1.65; P = 0.110, age >44 HR, 1.80; P = 0.056) but lower relapse risk (compared to age <30; age 30-44 HR, 0.61; P = 0.034, age > 44 HR, 0.71; P = 0.132). There were no differences in CRS, aGVHD or cGVHD. We found no difference in outcomes based on the donor-recipient relationship. No differences were found based on HLA match grade or DRB1 match status. Increasing donor age was associated with lower relapse risk but higher NRM, resulting in no difference in OS based on donor age. Other donor factors including relationship (parent/sibling/child/ maternal), CMV status, donor sex, HLA match grade, and DRB1 status were not associated with outcomes.
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7.
Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association (WMDA): WMDA Guidelines on Genetic Findings of Donor Origin
Pryce, A., Van, E. E., Cody, M., Oakes, J., DeSalvo, A., Bannon, S., Burlton, C., Pawson, R., Fingrut, W., Barriga, F., et al
Transplantation and cellular therapy. 2023
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Free full text
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Editor's Choice
Abstract
Following hematopoietic cell transplantation, recipients are subjected to extensive genetic testing to monitor the efficacy of the transplant and identify relapsing malignant disease. This testing increasingly includes the use of large gene panels which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor, can prove challenging. In response to queries from donor registries and transplant centers regarding best practice in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and to develop a framework to aid decision-making. These guidelines aim to provide recommendations on pre-donation consenting, post-donation testing of recipients and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognised that registries will have different access to resources and financing structures. Therefore, where possible, we have made suggestions on how recommendations can be adapted.
PICO Summary
Population
An expert group convened by the Medical Working Group of the World Marrow Donor Association
Intervention
Provide recommendations on pre-donation consenting, post-donation testing of recipients
Comparison
None
Outcome
These guidelines aim to provide recommendations on pre-donation consenting, post-donation testing of recipients and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation.
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8.
[ABO incompatibility and complications in hematopoietic stem cell transplantation]
Jiménez-Ochoa, M. A., Contreras-Serratos, M. M., González-Bautista, M. L., López-Macías, C., Torres-Fierro, A., Urbina-Escalante, E.
Revista medica del Instituto Mexicano del Seguro Social. 2023;61(Suppl 1):12-18
Abstract
BACKGROUND Hematopoietic stem cell transplants (HSCT) can be performed regardless of the ABO group compatibility between donor and recipient. ABO incompatibility in HSCT is related to pure red cell aplasia (PRCA), or passenger lymphocyte syndrome. The impact of ABO incompatibility on graft-versus-host disease and transplant-related mortality is controversial due to the heterogeneity of procedures carried out in different transplant centers. OBJECTIVE To determine the prevalence of ABO incompatibility and its complications in a hematopoietic stem transplant unit. MATERIAL AND METHODS An observational, retrospective study was carried out in patients undergoing HSCT from January 2014 to January 2020. All trasplant patients were included. Qualitative variables were analyzed using chi-squared test, and Wilcoxon and Student's t tests were used for quantitative variables. A p < 0.05 was considered significant. RESULTS 124 patients undergoing HSCT were analyzed, out of which 31 had ABO incompatibility, with a punctual prevalence of 24.4%; among them, 54% presented with major incompatibility, 32% minor incompatibility and 13% bidirectional incompatibility. Three cases of PRCA were reported. There were no differences in survival at one year in both groups. CONCLUSIONS The ABO incompatibility ant its complications were not related to the increase in mortality. Randomized prospective studies are required to define the role of ABO incompatibility in HSCT prognosis.
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9.
Effect of donor age in patients with acute myeloid leukemia undergoing haploidentical hematopoietic cell transplantation vary by conditioning intensity and recipient age
Saliba, R. M., Kanakry, C. G., Gadalla, S., Kebriaei, P., Rezvani, K., Champlin, R. E., Shpall, E. J., Weisdorf, D., Mehta, R. S.
American journal of hematology. 2023
Abstract
We investigated the impact of donor age (younger [≤35 years] vs. older [>35 years]) after accounting for other non-HLA and HLA factors on outcomes of patients with acute myeloid leukemia undergoing HLA-haploidentical hematopoietic cell transplantation (n = 790). The effect differed by conditioning-partly related to the differences in the recipient age in myeloablative (MAC; median 46 years) versus reduced-intensity/non-myeloablative conditioning (RIC/NMA; median 61 years) groups. With MAC (n = 320), donor age had no impact on acute graft-versus-host disease (GVHD), but older donors were associated with a significantly higher risk of chronic GVHD (hazard ratio [HR]: 1.6, 95% confidence interval [CI]: 1.10-2.30, p = .02) independent of recipient age and other factors. Donor age had no impact on either relapse or non-relapse mortality (NRM). The impact of donor/recipient age on overall survival changed over time. Older donors were associated with significantly higher late overall mortality (>6 months) in younger recipients (≤ 50 years; HR: 2.2, 95% CI: 1.03-4.6, p = .04) but not older recipients. With RIC/NMA (n = 470), neither recipient's nor donor's age influenced the risk of GVHD. Donor age had no significant impact on the risk of relapse, but older donors were associated with a significantly higher risk of NRM (HR: 1.6, 95% CI: 1.02-2.6, p = .04) independent of recipient age. Older donor age was associated with significantly higher late overall mortality (>9 months) in older recipients (>50 years; HR: 1.66, 95% CI: 1.0-2.67; p = .049) but not in younger recipients. Donor selection based on donor age may require a tailored approach for a particular recipient.
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Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP/-DQ on engraftment in cord blood transplantation
Jo, T., Arai, Y., Hatanaka, K., Ishii, H., Ono, A., Matsuyama, N., Mori, J., Koh, Y., Azuma, F., Kimura, T.
Cytotherapy. 2023;25(4):407-414
Abstract
BACKGROUND AIMS While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood. METHODS We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLA-DP and -DQ on CBT outcomes. RESULTS Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT. CONCLUSIONS Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units.