scholarly journals Impact of HLA class I allele-level mismatch on viral infection within 100 days after cord blood transplantation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tomoki Iemura ◽  
Yasuyuki Arai ◽  
Junya Kanda ◽  
Toshio Kitawaki ◽  
Masakatsu Hishizawa ◽  
...  
Keyword(s):  
Viral Infection ◽  
Cord Blood ◽  
Viral Infections ◽  
Cord Blood Transplantation ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Blood Transplantation

AbstractViral infection is more frequently reported in cord blood transplantation (CBT) than in transplantation of other stem cell sources, but its precise mechanism related to antiviral host defenses has not been elucidated yet. To evaluate the effect of human leukocyte antigen (HLA) class I allele-level incompatibility on viral infection in CBT, we conducted a single-center retrospective study. Total 94 patients were included, and viral infections were detected in 32 patients (34%) within 100 days after CBT. HLA-C mismatches in graft-versus-host direction showed a significantly higher incidence of viral infection (hazard ratio (HR), 3.67; p = 0.01), while mismatches in HLA-A, -B, or -DRB1 were not significant. Overall HLA class I mismatch was also a significant risk factor and the predictor of post-CBT viral infection (≥ 3 mismatches, HR 2.38, p = 0.02), probably due to the insufficient cytotoxic T cell recognition and dendritic cell priming. Patients with viral infection had significantly worse overall survival (52.7% vs. 72.1%; p = 0.02), and higher non-relapse mortality (29.3% vs. 9.8%; p = 0.01) at 5 years. Our findings suggest that appropriate graft selection as well as prophylaxis and early intervention for viral infection in such high-risk patients with ≥ 3 HLA class I allele-level mismatches, including HLA-C, may improve CBT outcomes.

Impact of HLA Class I Allele Mismatch on Viral Infection within 100 Days after Cord Blood Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3267-3267
Author(s):  
Tomoki Iemura ◽  
Yasuyuki Arai ◽  
Junya Kanda ◽  
Toshio Kitawaki ◽  
Masakatsu Hishizawa ◽  
...  
Keyword(s):  
Viral Infection ◽  
Research Funding ◽  
Viral Infections ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Hla Class I ◽  
Class I ◽  
Virus Infections ◽  
Blood Transplantation ◽  
Cmv Antigenemia

Introduction: Viral infections occur more frequently in cord blood transplantation (CBT) than in transplantation of other stem cell sources, and they are often fatal. Thus, it is important to determine the predictors of viral infection to improve CBT outcomes. We hypothesized that incompatibility of human leukocyte antigen (HLA) class I can increase susceptibility to viral infections because donor HLA-restricted naïve cytotoxic T cells cannot recognize recipient infected cells properly in the early term after CBT. Herein, we focused on the impact of HLA class I incompatibility on viral infection within 100 days after CBT. Patients and Methods: We retrospectively analyzed 121 patients who underwent 126 CBT procedures at Kyoto University Hospital from February 2003 to January 2019. Viral infection was defined as infection of recipient somatic cells by viruses detected via pathology or molecular biology and confined to those specific for an immunocompromised condition. Cytomegalovirus (CMV) antigenemia was distinguished from viral infections, because in such cases, the infected cells are donor-derived cells. Characteristics were compared between two groups using Fisher's test. The incidences of viral infection, CMV antigenemia, and steroid use for pre-engraftment immune reaction, engraftment syndrome, and acute graft-versus-host disease (aGVHD) together (PIR/ES/aGVHD) were calculated considering death and relapse as competing events, and they were compared using Gray's test. Fine-Gray proportional hazards models were used for univariate and multivariate analyses to evaluate the effects of variables on outcome. Survival was estimated using the Kaplan-Meier method. Non-relapse mortality was estimated using Gray's method. Results: The median patient age was 47 (range, 19-68) years, and 69 patients were male. The underlying diseases were acute myeloid leukemia (n=53), acute lymphoblastic leukemia (n=17), myelodysplastic syndromes (n=17), anaplastic anemia (n=6), non-Hodgkin lymphoma (n=20), and others (n=9). Regarding the CBT protocol, 44 patients received myeloablative conditioning and 83 patients received a calcineurin inhibitor and mycophenolate mofetil for GVHD prophylaxis. We identified 50 virus infections in 42 transplants within 100 days after transplantation, including 7 human herpesvirus 6 infections, 14 CMV infections, 26 BK virus, JC virus, and adenovirus infections, 2 varicella-zoster virus infections, and 1 unknown virus infection. Univariate analysis showed that HLA-A and HLA-C allele mismatches in the GVH direction were associated with a significantly higher incidence of viral infection (mismatch vs. match; HLA-A: 42.7% vs. 25.8%, HR 1.86, P=0.049; HLA-C: 43.9% vs. 17.6%, HR 2.94, P=0.015; Figure 1A). Moreover, 3/6 or more HLA class I allele mismatch in the GVH direction was associated with a significantly higher viral infection incidence (50.0% vs. 26.9%, HR 2.29, P=0.010; Figure 1B), but not with CMV antigenemia (65.8% vs. 70.1%, HR 0.95, P=0.82). These patients with HLA class I mismatches showed no increase in steroid use for PIR/ES/aGVHD (70.4% vs. 64.2%, P=0.53) or prophylactic antiviral drug therapy (62.5% vs. 65.7%, P=0.84). Regarding HLA class II mismatches, HLA-DR mismatch in the GVH direction was not associated with viral infection (34.1% vs. 32.6%, HR 1.13, P=0.72). Univariate analysis showed that lymphoid neoplasm (P<0.01), no use of cytarabine for conditioning (P=0.035), fludarabine and melphalan use for conditioning (P=0.043 and 0.075, respectively), and second or subsequent transplant (P=0.067) were associated with a higher incidence of viral infection. Multivariate analysis showed that HLA class I mismatches and lymphoid neoplasm remained significant factors for viral infection (P=0.035 and <0.01, respectively). Regarding post-CBT outcomes, 5-year overall survival (OS) and non-relapse mortality (NRM) with landmark analysis at 100 days were inferior in patients with viral infection (OS: 66.5% vs. 73.6%, P=0.35; NRM: 14.6% vs. 4.6%, P=0.11). Conclusion: HLA class I allele mismatch, including HLA-C mismatch, was significantly associated with viral infection within 100 days of CBT. Our findings suggest the importance of HLA class I genotype compatibility, including HLA-C compatibility, for CBT. Graft matching can reduce the incidence of viral infection and thus improve outcomes. Figure 1 Disclosures Kanda: Chugai: Honoraria; Otsuka: Honoraria; JCR Pharmaceuticals: Honoraria; Bristol-Meyers Squib: Honoraria; Kyowa Hakko Kirin: Honoraria; NextGeM Incorporation: Patents & Royalties: 2019-011392; MSD: Honoraria; Daiichi Sankyo Company: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Astellas: Honoraria. Takaori-Kondo:Chugai: Research Funding; Janssen: Honoraria; Pfizer: Honoraria; Kyowa Kirin: Research Funding; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ono: Research Funding; Takeda: Research Funding.

Late Viral Infections After Cord Blood Transplantation: Comparison with Unrelated Bone Marrow Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1260-1260 ◽  
Author(s):  
Yuki Asano-Mori ◽  
Hiroshi Shimazu ◽  
Kazuya Ishiwata ◽  
Nobuaki Nakano ◽  
Masanori Tsuji ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Influenza Virus ◽  
Stem Cell ◽  
Viral Infection ◽  
Cord Blood ◽  
Viral Infections ◽  
Cord Blood Transplantation ◽  
Parainfluenza Virus ◽  
Blood Transplantation ◽  
Unrelated Donors

Abstract Abstract 1260 Although the efficacy of cord blood transplantation (CBT) from unrelated donors as viable alternative for patients in need of hemtopoietic stem cell transplantation (HSCT) is supported by growing evidences, viral infections related to delayed immune reconstitution remains important problems for further improvement of clinical outcomes. To evaluate incidences and outcomes of late viral infections after CBT by comparison with those after unrelated bone marrow transplantation (uBMT), we retrospectively analyzed the records of 281 Japanese adult patients who underwent allogeneic unrelated HSCT for the first time at the Toranomon Hospital between January, 2002 and March, 2010, and who survived more than 100 days after HSCT without the lost-to-follow-up or retransplantation before day 100. Between 50 days and 5 years after HSCT, 116 patients had at least one late infectious episode with a cumulative incidence of 52.2%, at a median of 157 (50-1597) days after HSCT. The 5-year cumulative incidence of any late viral infections was greater in CBT versus uBMT recipients (60.7% vs. 42.2%, respectively; P=0.039, Figure 1). Thirty-three patients (28.4%) had 2 or more episodes caused by different viruses, and a total of 152 late infectious episodes were documented. The median onset of the episodes was similar between the both groups (median onset 226 days vs 222 days, P=0.89). The most common late viral infection is varicella-zoster virus (VZV) reactivation, accounting for 28.8% (disseminated 10, localized 34), followed by hemorrhagic cystitis associated with adeno- and/or BK viruria (28.2%), cytomegalovirus (CMV) diseases (16.4%; gastrointestinal diseases 23, retinitis 1, pneumonia 1), and respiratory tract infections caused by influenza virus, parainfluenza virus or respiratory syncytial virus (15.8%; upper 26, lower 8), and Epstein-barr virus lymphoproliferative diseases (4.6%). The remaining 10 infectious episodes were caused by relatively rare type of viruses including herpes simplex virus, JC virus, measles virus, mumps virus, norovirus and parvovirus, all of which occurred only in CBT recipients. Of all these viral infections, only VZV reactivation developed significantly more frequent in CBT than in uBMT recipients (P=34.0% vs 17.0%, P=0.023). There was no difference of dissemination rate between the both groups, and all the patients responded well to treatment with antiviral agents. The late viral infection was a primary cause of death in 3 episodes, all of which were pneumonia caused by CMV, influenza virus and parainfluenza virus. The 5-year incidence of infection-related mortality did not differ between CBT and uBMT recipients (0.7% vs 3.1%, P=0.46). Non-relapse mortality occurred in 11.8 % and 16.4 % patients in the CBT and uBMT groups (P=0.71). These findings suggested that cord blood might be as an acceptable and useful stem-cell source as bone marrow from unrelated donors in terms of risks of viral infection in the late posttransplant period. Disclosures: No relevant conflicts of interest to declare.

Viral Infection After Unrelated Cord Blood Transplantation In Bordeaux: Incidence and Outcomes. A Single Centre Experience with Eurocord.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4543-4543
Author(s):  
Pierre-Yves Dumas ◽  
Reza Tabrizi ◽  
Stephane Vigouroux ◽  
Marie-Edith Lafon ◽  
Gerald Marit ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Infection ◽  
Cord Blood ◽  
Viral Infections ◽  
Hemorrhagic Cystitis ◽  
Cord Blood Transplantation ◽  
Median Number ◽  
Bk Virus ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract Abstract 4543 Background: Umbilical cord blood is being increasingly used for transplantation, but the ability of neonatal T cells to regulate viral infections seems to be less effective than other stem cell sources. Viral infections remain important cause of morbidity after hematopoietic stem cell transplantation and some virus less monitored could be important pathogens. We performed a retrospective study, using the EUROCORD database, in 45 patients with the aim to analyze the incidence for viral infections in patients transplanted with single or double unrelated cord blood units for hematologic malignancies, during the first two years after transplantation. Methods: Patients received the unrelated umbilical cord blood transplantation at the Bordeaux University Hospital, France, between October 2003 and December 2009. Real-time quantitative polymerase chain reaction was used to measure the EBV and CMV load twice a week and only if presence of symptom for others virus. We included patients with one quantitative positive PCR in blood for EBV, CMV, HHV6 and ADV, one PCR positive for BK virus in urine, and clinical diagnosis for VZV recurrent infections. Herpes virus disease was defined as clinical symptom from the affected organ, combined with the detection of the herpes virus by PCR in organ biopsy or blood. Results: The median age was 41 years (range 8–63) with 5 patients (11.5%) < 15 years old. Among these 45 patients, 75% had acute leukemia or myeloid malignancies and 25% lymphoid malignancies. Administration of acyclovir for prevention of HSV and CMV infections was carried out in all patients. Grafts have been performed with a single unmanipulated cord blood unit in 73% and two unmanipulated units in 27%. Neutrophil and platelet recoveries were defined as the first of 2 consecutive days during which the ANC in the blood was >0.5×109/L and the platelet count was >20×109/L without transfusion support, median time to neutrophil recovery was 24 d (range 5–56 d) and median time to platelet recovery was 34 d (range 0–88 d). The median number of nucleated cells infused in recipients of cord blood was 2.2×107/kg of the recipient's body weight (range, 0.7×107 to 6.63×107/kg). The median number of CD34+ cells in the cord blood grafts was 0.9×105/kg (range, 0.16×105 to 3.4×105/kg). Conditioning varied according to the patient's disease and disease status with 45% myeloablative and 55% reduced intensity. All patients, except one, received a cyclophosphamide containing regimen and 24.4% patients received antithymocyte globulin prior to transplantation. Prophylaxis for acute GVHD consisted of cyclosporine A and MMF in 91%, cyclosporine A alone for 2 patients, with prednisone for 1 patient and with MTX for 1 patient. Among the whole cohort, we observed 77.7% viral infections: 9/45 experienced at least one positive PCR for EBV of whom 1 had lethal PTLD, 10/45 for CMV with one gastrointestinal disease and 25/45 for HHV6 with three encephalitis, two pneumoniae, five skin rash, three gastrointestinal infections manifested as diarrhea or hemorrhagic colitis, and two hepatitis. Furthermore, we observed 6/45 herpes zoster with one disseminated disease, 7/45 hemorrhagic cystitis resulting of BK virus infection and 3 patients who experienced ADV viremia. At 100 days the cumulative incidence (CI) for any viral infection was about 69%, 51% for HHV6 infection, 35% for HHV6 disease, 13% for CMV infection and disease, 18% for EBV infection, 14% for BK virus hemorrhagic cystitis, 5% for ADV infection and cumulative incidence at 200 days about 5% for VZV. Viral infection or disease did not affect significantly the overall survival of the patients. Conclusion: Among the various viral infection/diseases, the high CI of HHV6 infection/disease is of concern. Analysis of risk factors for infection and disease in this specific setting is in progress. Although the morbidity is high, thanks to close monitoring and prompt therapeutic intervention when possible, the mortality directly linked to viral infection remains low. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Haematologica ◽  
2016 ◽  
Vol 101 (5) ◽  
pp. e209-e212 ◽  
Author(s):  
N. Guillaume ◽  
P. Loiseau ◽  
K. Gagne ◽  
H. Moins-Teissserenc ◽  
J.-M. Cayuela ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Cord Blood ◽  
Natural Killer ◽  
Cord Blood Transplantation ◽  
Killer Cell ◽  
Hla Class I ◽  
The Self ◽  
Class I ◽  
Blood Transplantation ◽  
Hla Class I Molecules

scholarly journals Mislabeled units of umbilical cord blood detected by a quality assurance program at the transplantation center

Blood ◽  
2009 ◽  
Vol 114 (8) ◽  
pp. 1684-1688 ◽  
Author(s):  
Jeffrey McCullough ◽  
David McKenna ◽  
Diane Kadidlo ◽  
David Maurer ◽  
Harriett J. Noreen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hla Typing ◽  
Class I ◽  
Quality Assurance Program ◽  
Cord Blood Unit ◽  
Transplantation Center

Abstract We instituted procedures to check the identity of cord blood unit provided for transplantation by carrying out ABO and human leukocyte antigen (HLA) typing of the thawed units before transplantation. ABO typing is done using standard techniques. Rapid HLA class I serology is with monoclonal antibody trays (One Lambda Inc) using standard incubations. One mislabeled umbilical cord blood (UCB) unit was detected on the day of intended transplantation by repeat ABO typing of the thawed unit at our transplantation center. Because ABO typing will not detect all labeling errors, the rapid serologic class I HLA typing procedure was done on thawed units just before transplantation for all units without an attached segment. This procedure identified a second mislabeled unit. In a 6-year period, 2 of 871 (0.2%) cord blood units sent to us for transplantation were mislabeled and potentially would have been transplanted incorrectly. This error rate of 1 per 249 (0.4%) patients could have potentially devastating consequences.

High Expression of Granzymes and Perforin along with Increased T cell Cycling In Vivo Predicts the Development of Opportunistic Infections (OI) Following Unrelated Cord Blood Transplantation (UCBT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2238-2238
Author(s):  
Paul Szabolcs ◽  
Young-Ah Lee ◽  
Luciana Marti ◽  
Melissa Reese ◽  
Joanne Kurtzberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Cord Blood Transplantation ◽  
Ki 67 ◽  
Granzyme A ◽  
Blood Transplantation

Abstract Introduction: Unrelated umbilical cord blood transplantation (UUCBT) is a viable option for those who lack HLA-matched sibling donors. However, opportunistic infections (OI) occurring in the first 100 days, remain the major cause of morbidity and mortality. Viral infections are the primary cause of OI death. As previously shown, cord blood T cells have significantly less preformed effector molecules available intracellularly to kill virally infected cells via the perforin-granzyme pathway than adult PB T cells. Since several virally infected patients control their infections in the absence of specific antiviral therapy ( e.g adenoviral enteris, polyoma cystitis) we postulated that the T cell compartment of those UUCBT recipients who experience early viral infections maty upregulate expression of the perforin exocytosis pathway. In parallel the impact of viral infection on T cell turnover would also be appreciable. Here we report on 19 prospectively studied pediatric patients, all full donor chimera, following myeloablative therapy. Methods: On day +50 we determined by 4-color FACS the expression of intracellular Granzyme, A, B, along with perforin. To monitor T cell turnover proliferating cells were identified by monitoring for the KI-67 nuclear antigen. The expression of the antiapoptosis gene BCL-2 was similarly monitored in both CD4+ and CD8+ T cells. We analyzed their association with the development of de novo OI up to day +100 employing Student’s t-test. Results: Mean age of patients was 6.2 years. 10 of 19 patients developed OI (adenovirus x 4, CMV x 7, EBVx1, parainfluenza x 1) with 5/10 patients experiencing more than one viral infections simultaneously) at a median of 29 days after UUCBT. Of those with OI 6/10 died due to their infections while 8/9 without OI are alive at a median of 15.8 months after UUCBT with one death due to leukemic relapse. Table I presents the correlation between the tested parameters with the development of OI. Patients experiencing viral infections had significantly higher % of their T cells in particular CD8+ T cells equipped with effectors of cytotoxicity and were proliferating in higher percentage compared to those with no active infections. However, the anti-apoptotic protein BCL-2 expression was significantly lower in patients experiencing OI that may lead to their shorter life span and overall T cell lymphopenia observed in OI patietns that we have previously detected in a larger cohort of 102 patients (ASBMT 2004 abstract#48). Conclusion: Correlating with active viral infections significant maturation of cord blood T cells is evident as early as 50 days after UUCBT towards acquiring effector molecules of the perforin pathway. Enhanced T cell proliferation is counteracted by reduced expression of BCL-2 that may lead to the lymphopenia in patients with OI. Future strategies aiming to enhance the longevity of antiviral T cells may protect from death due to viral infections. Univariate analysis VARIABLE MEDIAN VALUE FOR PATIENTS WITH OI MEDIAN VALUE FOR PATIENTS WITHOUT OI t-Test p value % Granzyme A+ T cells 52% 9% 0.006 % Granzyme A+ CD8+ T cells 91% 47% <0.001 % Granzyme B+ T cells 36% 6% 0.036 % Granzyme B+ T cells 87% 39% <0.001 % Perforin+ T cells 38% 4% 0.009 % Perforin+ CD8+ T cells 61% 21% <0.001 % Ki-67+ T cells 27% 16% 0.0041 % Ki-67+ CD8+ T cells 35% 16% 0.0037 BCL-2 expression level (MFI) 87 117 0.028

High Resolution HLA Typing by Sequencing for HLA-A, B, C, DR, DQ in 115 Unrelated Cord Blood/Patient Pairs- Does It Improve Outcomes after Cord Blood-Transplantation?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 973-973 ◽  
Author(s):  
Gesine Koegler ◽  
Juergen Enczmann ◽  
Vanderson Rocha ◽  
Eliane Gluckman ◽  
Peter Wernet
Keyword(s):  
High Resolution ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Hla Class I ◽  
Hla Typing ◽  
Class I ◽  
Published Data ◽  
Number Of Patients ◽  
The Impact ◽  
Grade Iii

Abstract The CB Bank Düsseldorf has provided to date (July 2004) 224 CB units (216 unrelated and 8 related, 29% adults, 71% children) to transplant centers worldwide. Until now no correlation could be detected between the number of HLA-mismatches based on low resolution (LR) typing for HLA-A and-B and high resolution typing (HR) for DRB1 and the incidence of aGvHD as published previously by us and other groups. The lack of correlation between aGvHD occurrence and donor/recipient HLA diversity in patients given an unrelated CBT could be explained by the fact that some mismatches for HLA class I antigens (A, B and C) are not detected by LR typing. In order to determine the impact of HLA high resolution typing with outcomes, mainly aGvHD after UCBT we analysed DNA samples of 115 CB recipients (86 children; 29 adults; 66 male, 49 female; diagnosis ALL=43, AML=19, SecAL =1, MDS=5, CML=10, NHL=5, Hodgkin=1, AA=7, genetic and metabolic diseases= 24) and their unrelated CB grafts were HLA-typed for HLA-class I (A, B, C) and HLA-class II (DRB1 and DQB1) by sequencing. The transplant centers used their own protocols for GvHD prophylaxis, the most commonly used was the combination of CsA and steroids alone (60%), CsA alone (15%), or the combination with MTX (6%). 55 of 115 patients did not develop aGvHD (grade 0= 48%), 26 patients developed grade I (23%), 12 patients developed grade II (10%), 10 patients grade III (9%) and 12 patients grade IV (10%). When mismatches (MM) were analysed for HLA-A, B based on LR-typing and -DRB1 based on HR-typing in concordance with all published data so far, the following mismatch situation resulted: No MM (16 pairs, 13.9%), one MM (47 pairs, 40.9%), two MM (41 pairs, 35.7%), three MM (5 pairs, 4.3%), four MM (3 pairs, 2.6%). If the MM for A and B alleles detected by HR-typing were included, the situation was as follows: 0 MM (6 pairs, 5.2%), 1 MM (35 pairs, 30.4%), 2 MM (54 pairs, 47%), 3MM (14 pairs, 12.2%), 4 MM (5 pairs, 4.3%), 5 MM (1 pair, 0.9%). If analysing A, B, C, DR and DQ based on HR typing a high additional frequency of MM occurred: No MM (4 pairs, 3.5%), 1 MM (13 pairs, 11.3%), 2 MM (19 pairs, 16.5%), 3 MM (24 pairs, 20.9%), 4 MM (30 pairs, 26.1%), 5 MM (14 pairs, 12.2%), 6 MM (6 pairs, 5.2 %), 6 MM (6 pairs, 5.2%), 7 MM (3 pairs, 2.6%), 8 MM (2 pairs, 1.7%). There was no significant correlation between the number of MM (also analysed in GvHD or rejection direction) using high-resolution level for HLA-A, B and DRB1 as well as for HLA-A, B, C, DRB1 and DQB1 and the development of aGvHD grade III-IV. More interestingly, we have not found any significant correlation between numbers of MM with 2-year survival probability. Although the heterogeneity and number of patients analysed, it shows that the degree of mismatching is even higher than expected, also in comparison to unrelated BMT. It also shows that additional subtyping for HLA-A, B, C and DQ, not performed on a routine basis at present, does not improve the 2-year survival rate.

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
Keyword(s):  
New York ◽  
Human Leukocyte Antigen ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Leukocyte Antigen ◽  
Blood Transplantation ◽  
Cord Blood Unit ◽  
Unrelated Cord Blood

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.

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