ABO-mismatched Transplantation Research Articles

ABO incompatibility haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit for severe aplastic anemia patients.

To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients with donor-recipient ABO incompatibility. This was a retrospective cohort study and data of 57 severe aplastic anemia patients underwent haploidentical stem cell transplantation from August 1, 2018 to February 28, 2022 in the First Affiliated Hospital of Xi'an Jiaotong University was retrospectively analyzed. All patients were divided into two groups, the donor-recipient ABO matched group (bone marrow+peripheral blood group) using haploidentical bone marrow and peripheral blood stem cells as grafts, and donor-recipient ABO mismatched group (cord blood+peripheral blood group), using unrelated cord blood and haploidentical peripheral blood stem cells as grafts. The differences of hematopoietic reconstitution, acute and chronic graft-versus-host disease, Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and overall survival between the two groups were compared. There were 30 cases in cord blood+peripheral blood group and 27 cases in bone marrow+peripheral blood group. One patient in bone marrow+peripheral blood group had primary graft failure, while other patients were successfully implanted. There were no significant differences of neutrophil and platelet recovery rates between two groups. The erythrocyte recovery time of cord blood+peripheral blood group was slower than that of bone marrow+peripheral blood group (p < 0.05). There was no significant difference of the incidence of graft-versus-host disease, CMV, EB virus infection and post-transplant lymphoproliferative disorders between two groups (p > 0.05). The incidence of grade III-IV acute graft-versus-host disease in cord blood+peripheral blood group was higher than that of bone marrow+peripheral blood group (p < 0.05). The incidence of intestinal graft-versus-host disease was higher in minor ABO-mismatched transplantation than that in major ABO-mismatched transplantation (p < 0.05). There was no significant difference of overall survival between two groups (p > 0.05). These findings suggest that haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit may be an alternative option for severe aplastic anemia patients with donor-recipient ABO incompatibility.

Pre-transplant donor-type red cell transfusion is a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants.

ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.

The Potential Significance of ABO Genotyping for Donor Selection in Kidney Transplantation

BackgroundThe ABO blood group system is clinically important in kidney transplantation, but ABO genotyping fails to attract sufficient attention in some countries and regions. We identified one case of early graft dysfunction due to an ABO genotype mismatch. Here, we performed ABO genotyping in blood samples, analyzed grouping discrepancies, and investigated the weak A subgroup frequency in kidney transplantation candidates.MethodsBlood samples from 302 uremic patients with grouping discrepancies and 356 uremic patients with type A blood were analyzed using standard serologic serotyping techniques. The ABO genotypes and alleles were analyzed by polymerase chain reaction sequence-specific primer (PCR-SSP) and sequence-based typing (PCR-SBT).ResultsAll 302 uremic patients with grouping discrepancies carried weak ABO subgroup alleles and 77.48% carried irregular ABO antibodies. The discrepancy rate between serotyping and genotyping was 42.38%, and the mismatching rate of donor selection according to serotype reached 88.74%. And 2.53% of 356 uremic patients with type A blood were determined to be in the weak A subgroup, which was a higher percentage than that observed in the healthy Chinese population (0.53%) by serological screening, but much lower than that observed in Caucasians (20%).ConclusionWe revealed the high risk of blood type misjudgment and genetically ABO-mismatched transplantation if serological test was performed only in blood-group typing. Improved precision of ABO genotyping is crucial for successful kidney transplantation and reasonable organ allocation.

Impact of ABO Blood Group Incompatibility on Outcomes after Single-Unit Umbilical Cord Blood Transplantation for Malignant Hematological Disease

Objective In contrast to solid organ transplantation, ABO blood group incompatibility was acceptable in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, reports of the effect of donor-recipient ABO incompatibility on long-time survival, graft-versus-host disease (GVHD), and relapse after allo-HSCT were controversial. Relatively few reports existed on the effects of ABO incompatibility after umbilical cord blood transplantation (UCBT). The aim of this study was to investigate the role of major ABO incompatibility on RBC transfusion burden, hematologic recovery, GVHD, transplant-related mortality (TRM), relapse, and overall survival (OS) in UCBT for malignant disease. Methods This retrospective study included 587 malignant hematonosis patients who received myeloablative single-unit unrelated donor UCBT at our center between May 2008 and June 2018. Median follow-up time of the patients alive was 40.7 months (range: 12.0-134.6 months). A total of 230 (39.2%) patients received an ABO-identical transplant, and 357 (60.8%) received ABO-mismatched transplants, including 161 (27.4%) minor, 141 (24.0%) major, and 55 (9.4%) bidirectional ABO-incompatible UCBTs. All patients received myeloablative conditioning regimens and cyclosporine A (CsA) combined with mycophenolate mofetil (MMF) as a GVHD prophylaxis. Results A comparison of ABO compatibility and incompatibility demonstrated no significant differences (P&gt;0.05) in the cumulative incidence of neutrophil, platelet, and red blood cell engraftment . There was no significant difference in the cumulative incidence of grades Ⅱ to Ⅳ aGVHD (P= .527) and Ⅲ to Ⅳ aGVHD (P= .949) among the 4 groups (Figure A , B). In univariate analysis, ABO blood group incompatibility was not associated with cumulative incidence of 180d TRM (Figure C, P= .602). The overall 3-year survival had no statistically significant differences among the 4 groups (Figure D; P= .384). Further, 11 patients were excluded from the analysis of post-UCBT RBC transfusion burden because of missing data and non-red blood cell engraftment. Of the remaining 576 patients, the median number of RBC transfusions during transplant days 0 to 60 was 4 (range, 0 to 106). There was no significant difference in the transfusion burden among all ABO blood type mismatch groups (Table 1, P = .069). Furthermore, none of the patients developed pure red aplastic anemia (PRCA) after UCBT. Conclusion The results showed that ABO blood group incompatibility had no significant impact on hematologic engraftment, the occurrence of GVHD, and the survival of malignant hemoblastosis. Patients with myeloablative single-unit UCBT may not develop PRCA; Donor-recipient ABO incompatibility may not be the major consideration in the selection of umbilical cord blood. Disclosures No relevant conflicts of interest to declare.

Impact of ABO Mismatch on Outcomes of Allogeneic Hematopoietic Stem Cell Recipients: 30 Years of Experience with 1016 Patients

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant and non-malignant hematological diseases.The impact of ABO mismatch on outcome following transplantation remains controversial.In this study, our aim is to define effects of ABO mismatch on engraftment, graft vs host disease, relapse free survival (RFS) and overall survival (OS) in patients who underwent allo-HSCT. Patients and Methods Between 1988 and 2016, we retrospectively identified 1016 patients who underwent allo-HSCT at Ankara University School of Medicine, Department of Hematology.Chi-square and FisherOs exact tests were used where appropriate in comparison.Cox regression model and Kaplan Meier curves were applied for survival analysis.P Results The median follow-up period was 34.7 months (range, 0.2-229).In our cohort, there were 420 (41.3%) ABO-mismatched transplants occurred including 167 (16.4%) major, 197 (19.4%) minor and 55 (5.4%) bidirectional mismatches.The pre-transplant characteristics of patients are summarized in Table.Allo-HSCTs from unrelated donors and peripheral blood grafts were detected higher in ABO mismatched patients vs ABO matched patients (28% vs 11%, P 1/128). Pure red cell aplasia was diagnosed in 5 (3%) major ABO mismatched patients.Major ABO mismatch (HR:1.46, 95% Cl:1.06-2.03;P=0.022) was found to be related with lower RFS and OS (HR:1.31, 95% Cl:1.06-1.62;P=0.013).3-year OS and 1-year RFS were lower with major ABO mismatch (38% vs 47%, P=0.02; 15% vs 24%; P=0.02) (Figure). Conclusion Engraftment failure was detected higher with ABO mismatch as well as major ABO mismatch was related with lower RFS and OS although the cohort is heterogeneous.Close monitoring and early treatment strategies for expectable complications would reduce the number fatal events by ABO mismatched allo-HSCT.

Impact of ABO Mismatch on Outcomes of Allogeneic Hematopoietic Stem Cell Recipients: 30 Years of Experience with 1016 Patients

Introduction:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant and non-malignant hematological diseases. The impact of ABO mismatch on outcome following transplantation remains controversial. In this study, our aim is to define effects of ABO mismatch on engraftment, graft vs host disease, relapse free survival (RFS) and overall survival (OS) in patients who underwent allo-HSCT.Patients and Methods:Between 1988 and 2016, we retrospectively identified 1016 patients who underwent allo-HSCT at Ankara University School of Medicine, Department of Hematology. Chi-square and Fisher's exact tests were used where appropriate in comparison. Cox regression model and Kaplan Meier curves were applied for survival analysis. P<0.05 was considered as statistically significant.Results:The median follow-up period was 34.7 months (range, 0.2-229). In our cohort, there were 420 (41.3%) ABO-mismatched transplants occurred including 167 (16.4%) major, 197 (19.4%) minor and 55 (5.4%) bidirectional mismatches. The pre-transplant characteristics of patients are summarized in table. Allo-HSCTs from unrelated donors and peripheral blood grafts were detected higher in ABO mismatched patients vs ABO matched patients (28% vs 11%, P<0.0001; 78% vs 67%, P<0.0001). The engraftment failure was higher in ABO mismatch group compared to ABO matched group (67 (16%) vs 70 (11%), P=0.05). Neutrophil and platelet engraftment rates were not statistically different in major, minor or bidirectional ABO mismatched vs matched donors. The acute graft vs host disease (GVHD) and chronic GVHD incidences did not alter in patients with ABO match and mismatch (44% vs 45%, P=0.78; 41% vs 39%,P=0.81). In ABO-mismatched group, hemolysis after infusion of graft occurred in 50 patients (12%) whereas during engraftment in 35 patients (8%). Although not statistically significant, hemolysis were occurred higher in major ABO mismatch. Plasma exchanges were performed in 18 patients in the major ABO mismatched group due to high anti-donor type isoagglutinin titers (≥1/128). Pure red cell aplasia was diagnosed in 5 (3%) major ABO mismatched patients. Major ABO mismatch (HR:1.46, 95% Cl:1.06-2.03;P=0.022) was found to be related with lower RFS and OS (HR:1.31, 95% Cl:1.06-1.62;P=0.013). 3-year OS and 1-year RFS were lower with major ABO mismatch (38% vs 47%, P=0.02; 15% vs 24%; P=0.02) (Figure).Conclusion:Engraftment failure was detected higher in patients with ABO mismatch as well as major ABO mismatch was related with lower RFS and OS although the cohort is heterogeneous. Close monitoring and early treatment strategies for expectable complications would reduce the number fatal events by ABO mismatched allo-HSCT. [Display omitted] DisclosuresCivriz Bozdag:NOVARTIS: Consultancy; MSD: Research Funding; TAKEDA: Consultancy. Özcan:Abbvie: Other: Travel payment; Bayer: Research Funding; MSD: Other: travel support, Research Funding; Roche: Honoraria, Research Funding; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Novartis: Research Funding; Jazz: Other; Jazz: Other: Travel support; Archigen: Research Funding; Celgene: Other: Travel support, Research Funding; MSD: Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding. Beksac:Deva: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ilhan:Roche: Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau.

ABO blood group antigen mismatch has an impact on outcome after allogeneic peripheral blood stem cell transplantation

ABO blood group antigen incompatibility (ABO mismatch) is not an obstacle to allogeneic stem cell transplantation (allo-SCT). However, the impact on clinical outcome after allo-SCT remains controversial. We analyzed 512 patients after allogeneic peripheral blood SCT (allo-PBSCT) for an association of ABO mismatch with transfusion requirements, myeloid and platelet engraftment, the incidence of GvHD, relapse, transplant-related mortality (TRM), and overall survival (OS). A total of 260 patients underwent ABO-mismatched transplantation and the control group consisted of 252 patients with ABO-matched allo-PBSCT. We found a significant association between major-0 ABO mismatch (group 0 recipient/group A, B, or AB donor) and increased red blood cell (RBC) and platelet transfusion requirements (both P<.001) as well as delayed platelet engraftment (P<.001). Minor-A (group A recipient/group 0 donor) and minor-AB (group AB recipient/group 0, A, or B donor) ABO mismatch was significantly associated with an increased TRM after allo-PBSCT (P=.001 and P=.02). In multivariate analysis performed using Cox regression, minor ABO mismatch appeared as independent risk factor for TRM after allo-PBSCT. No association was found for ABO mismatch with the incidence of GvHD, relapse, and OS. Our results suggest that ABO blood group mismatch has a significant impact on the outcome and that minor-A and minor-AB ABO mismatch represents a risk factor for increased TRM after allo-PBSCT.

Impact of ABO-Mismatch on Treatment Outcome and Transfusional Needs in Non-Myeloablative, Allogeneic, Peripheral Blood Stem Cell Transplantations

Background: Suitable stem cell donors are selected by HLA-typing, CMV status, gender and age. The ABO blood groups are not part of the initial search and selection process. Since ABO-antigens are inherited independently from HLA antigens, patient-donor mismatches may occur and are considered acceptable. However, with the increased use of unrelated donors, more ABO-mismatched transplants are expected to take place. The influence of ABO-mismatched transplants on clinical outcomes has been studied earlier, but is still under debate. Comparisons between studies are challenging because of the heterogeneity of patient populations, conditioning regimes, various stem cell sources and different outcome parameters. Only a few studies have evaluated transfusional needs after ABO mismatched stem cell transplantations.Aim: To gain insight in the impact of ABO-(mis) matching on red blood cell (RBC) transfusion dependency in the first 90 days after transplant and on clinical outcome after 1 year follow-up.Study design and methods: All patients treated from 2004 till 2014 with a first, allogeneic, peripheral blood derived stem cell transplantation after a reduced-intensity conditioning regimen, were included for analyses of treatment outcomes and transfusional needs.Results: In the population for treatment outcome analysis (n=233), 124 patients were ABO-identical, 31 were ABO-major mismatched and 68 were ABO-minor mismatched. Ten patients had a bidirectional ABO-mismatch and were excluded from analyses. Multivariate analysis showed no impact of ABO-mismatch on overall survival, acute graft-versus-host disease (GVHD) incidence, non-relapse related mortality (NRM) and GVHD-related mortality. The minor ABO-mismatch group had more relapse related mortality (RRM) after 1 year (26.5%) compared to the ABO-identical (12.1%, P=0.01) and the ABO-major mismatched group (6.4%, P=0.04). The hazard ratio (HR) for RRM in ABO-minor mismatch patients versus ABO-identical patients was 2.41 (95% confidence interval, 1.14 to 5.08, P=0.021). In the population for transfusion analysis (n=204), 111 patients were ABO-identical, 27 were ABO-major mismatched and 57 were ABO-minor mismatched. Nine patients had a bidirectional ABO-mismatch and were excluded from analyses. No influence of ABO-mismatch on transfusional needs was seen in the first 30 days after transplant. 30-60 days after transplant, 14 (52%) major ABO-mismatched patients needed RBC transfusions with an overall mean of 2.19 RBC units compared to 24 (22%) patients with an overall mean of 0.68 in the ABO-identical group (P=0.001) and 16 patients (28%) with an overall mean of 1.04 in the ABO-minor mismatched group (P=0.028). More than five transfusions were given to 15% of the major ABO-mismatch group, compared to only 3% in the ABO-identical group (Relative risk (RR) 5.0, 95% CI 1.2-21.0, P=0.028) and 5% in the minor ABO-mismatch group (RR 2.8, 95% CI 0.7-11.7, P=0.155). 60-90 days after transplant, the ABO-major mismatch group was still significantly more transfusion dependent with 13 patients needing transfusions (48%) and an overall mean of 2.33 RBC units per patient, compared to 23 patients (21%) with a mean of 1.04 units in the ABO-identical group (P=0.002) and 9 patients (16%) with an mean of 0.58 in the ABO-minor mismatch group (P=0.002). In this period,19% of ABO-major mismatch patients received more than 5 transfusions, compared to 6% in the ABO-identical group (RR 2.9, 95% CI 1.0-8.5, P=0.048) and 2% in the ABO-minor mismatch group (RR 10.6, 95% CI 1.3-86.0, P=0.028). Differences in transfusional needs remained significant regardless of pre-transplant hemoglobin levels. Pure red cell aplasia (PRCA), defined as transfusion dependency from day 30 until longer than day 90 after transplant, was seen in 10 patients with an ABO-major mismatch (37%).Conclusion: ABO-major mismatched patients needed significantly more RBC transfusions in the second and third month after transplant. More relapse related mortality was seen in the minor mismatch group. However, this is probably an artefact due to relatively small patient numbers. Other measures for treatment outcome showed no significant differences. Our results confirm that ABO-matching is not mandatory in donor selection for stem cell transplantation. Still, whenever possible ABO major mismatching should be preferably avoided to decrease transfusion burden. DisclosuresNo relevant conflicts of interest to declare.

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

ABO-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for a variety of malignant and non-malignant hematological and congenital diseases. Due to the fact that the human leukocyte antigen system is inherited independently of the blood group system, approximately 40-50% of all HSCTs are performed across the ABO blood group barrier. The expected immune-hematological consequences after transplantation of an ABO-mismatched stem cell graft are immediate and delayed hemolytic complications due to presence of isohemagglutinins or passenger lymphocyte syndrome. The risks of these complications can partially be prevented by graft manipulation and appropriate transfusion support. Dependent on the kind of ABO mismatch, different effects on engraftment have been observed, e.g. delayed red blood cell recovery and pure red cell aplasia. Data on incidence of acute graft-versus-host disease (GVHD), non-relapse mortality, relapse, and overall survival are inconsistent as most studies include limited patient numbers, various graft sources, and different conditioning and GVHD prophylaxis regimens. This makes it difficult to detect a consistent effect of ABO-mismatched transplantation in the literature. However, knowledge of expectable complications and close monitoring of patients helps to detect problems early and to treat patients efficiently, thus reducing the number of fatal or life-threatening events caused by ABO-mismatched HSCT.

Bortezomib Is Highly Effective For Pure Red Cell Aplasia After ABO-Incompatible Hematopoietic Stem Cell Transplantation

Introduction Pure red cell aplasia (PRCA) is an uncommon complication of ABO-incompatible hematopoietic stem cell transplantation. It is characterized by anemia, reticulocytopenia and absence of erythroid precursors in a morphologically normal-appearing bone marrow. Most cases of PRCA resolve spontaneously within weeks to months. A small subset of patients has a protracted disease course requiring continued red blood cell (RBC) transfusions. There is no approved standard of care for PRCA. Tapering of immunosuppressives such as steroids and calcineurin inhibitors, plasma exchange, rituximab, and anti-thymocyte globulin have all been employed with varying success rates. We report a case of PRCA after ABO-incompatible transplant that responded remarkably to treatment with bortezomib. Case Presentation A 60 year old female received a non-myeloablative HLA-matched ABO-mismatched sibling donor transplant for lenalidomide-refractory myelodysplastic syndrome (5q-). She received fludarabine/busulfan conditioning and tacrolimus/methotrexate for GVHD prophylaxis. The donor was blood type A Rh-positive and the recipient was O Rh-positive. The patient's post-transplant course was complicated by delayed engraftment, thrombocytopenia and autoimmune hemolytic anemia. When seen at our institution 22 months post-transplant, she had transfusion-dependent anemia requiring RBC transfusions every 2-3 weeks and reticulocytopenia. Bone marrow biopsy showed erythroid aplasia and preserved hematopoiesis in other cell lines, dysplasia was absent and parvovirus testing was negative. The patient had evidence of complete engraftment based on short tandem repeat analysis. Blood typing reflected transfused type O Rh-negative RBCs. Neither A cells from the donor nor Rh-positive cells from the patient were detected. High titers of anti-A and anti-B isohemagglutinins were detected despite transfusion with washed RBCs to reduce passive transfer. She was treated with prednisone 60mg/day, rituximab 375 mg/m2 weekly x4 and methylprednisolone 1g weekly x6 without response. Eventually, all immunosuppressive medications were discontinued to induce a graft versus recipient response. Two subsequent bone marrow biopsies continued to show nearly absent erythropoiesis, and the rare erythroid cells present lacked the blood group A antigen. Since PRCA was thought to be due to the recipient's plasma cells making anti-A antibodies, bortezomib, a potent inducer of apoptosis in plasma cells, was initiated. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly x4. The patient responded well to therapy. A month after completion of bortezomib, the patient's hemoglobin measured 12.1 g/dL, reticulocyte count was 174 x109/L and IgM and IgG anti-A titers were both &lt; 1. Bone marrow biopsy showed relative erythroid hyperplasia, and the majority of the erythroid precursors expressed blood group A. The patient continues to do well and at the time of her most recent evaluation, her hemoglobin was 13.9 g/dL. She has also remained transfusion-independent. Discussion PRCA after major ABO-incompatible transplant is thought to be caused by persistence of recipient plasma cells that continue to secrete anti-donor isohemagglutinins. Antibody titers may remain elevated for a longer duration in patients receiving non-myeloablative preparatory regimens. Bortezomib is a proteasome inhibitor that selectively induces apoptosis in plasma cells. Bortezomib has been used successfully to treat anti-body mediated rejection in both renal and liver transplant patients. A case of PRCA following ABO-mismatched hematopoietic transplant that was successfully treated with IV bortezomib has also been reported. To our knowledge, this is the first reported case of isohemagglutinin-mediated PRCA after ABO-mismatched transplant that responded favorably to subcutaneous bortezomib. Limitation The lack of long-term follow-up data precludes any assessment about the durability and persistence of response to bortezomib. Conclusion Bortezomib is an effective treatment for patients with PRCA mediated by residual host isohemeagglutinins after ABO-incompatible hematopoietic transplantation. Disclosures: Off Label Use: Our presentation describes the use of bortezomib for treatment of pure red cell aplasia after ABO-incompatible hematopoeitic stem cell transplantation. Vercellotti:Sangart Inc.: Research Funding; Seattle Genetics, Inc.: Research Funding.

Immune adsorption of anti-A/B antibodies prior to ABO-mismatched kidney transplantation: The Leiden experience

With the limited numbers of deceased donor organs available for organ transplantation, living donors are currently the main source for kidney transplantation. Major ABO incompatibility between the donor kidney and recipient provides an immunological barrier for direct donation. To overcome the ABO-mismatch barrier, naturally occurring, boosted anti-A and/or anti-B antibodies can be removed from the patient before and after kidney transplantation to prevent acute humoral mediated rejection. In 2010 ABO-incompatible kidney transplants were started in our hospital based on the Swedish protocol from the Karolinska University Hospital.

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation

Living-donor lobar lung transplantation (LDLLT) has been successfully performed in Japan. In LDLLT, the recipient usually receives one lower lobe from each of two donors; however, finding two ABO-matched donors is often difficult. Solid organ transplants from donors with minor ABO-mismatches can be complicated by hemolysis. We investigated the incidence of de novo anti-ABO antibody production and hemolysis in patients receiving LDLLT across minor ABO-mismatches. We evaluated 23 patients who underwent LDLLT between June 2008 and December 2011, including 11 patients who underwent minor ABO-mismatched transplantation. We measured the anti-A/B antibody serum titers, hemoglobin concentrations and indirect bilirubin levels. None of the patients showed any clinical signs of hemolytic anemia (mean follow-up period; 16 months). Two of the 11 patients (18 %) receiving minor ABO-mismatched LDLLTs showed a small amount of de novo anti-B antibodies for a transient period. These patients showed gradual progression of anemia, and weak de novo anti-A/B antibodies were detected with column agglutination technology. The patients received only 2 U of washed type O red blood cells; thereafter, the hemolytic anemia did not develop further in either case. LDLLT across minor ABO-mismatches results in the transient appearance of weak de novo anti-A/B antibodies with a low incidence; thus, this procedure can be a safe treatment.

Donor-Cell Leukemia After Hematopoietic Stem Cell Transplant: a Retrospective Review of a Single Center's Experience

Abstract 1997Donor-cell leukemia (DCL) is a rare complication of allogeneic hematopoietic stem cell transplant (ASCT) with a reported incidence varying from 0.1% to 5.0% of all post-transplantation relapses. However, the incidence is likely to be highly underestimated due to the difficulty in making the diagnosis. In the 1970s and 1980s, diagnosis of DCL relied on cytogenetic and fluorescence in situ hybridization studies in sex-mismatched donor/recipient pairs. Recent advances in molecular-based laboratory methods have considerably improved our ability to identify and confirm DCL in ASCT patients, especially when there is not a sex-mismatch between donor and recipient. Recently, an algorithm has been proposed by Wang et al. 2011 (Am J Clin Pathol 135;525–40) to help make the diagnosis of DCL in ASCT patients who develop overt leukemia or a clonal cytogenetic abnormality using these new advanced techniques. We retrospectively evaluated all patients who underwent ASCT at our center for acute leukemia from 2005 to present. Out of 43 patients, 6 apparent DCLs were documented using short tandem repeat (STR) analysis (12 separate loci examined); each ASCT patient relapsed with the full complement of donor STRs. Our data confirms that the true incidence of DCL is likely underestimated, since within our select population, we had a 14% incidence of DCL. Of note, 1/6 were sex mismatches, 3/6 received cord blood transplants, 4/6 cases were ABO mismatches, and 4/6 cases were AML (Table 1). Our findings concur with sparse available reports in the literature that purport there may be a shorter time to relapse in patients who are undergoing ASCT for malignant reasons; indeed, our average latency period was 14 months as opposed to 24 months found by Wang et al. However, we did not find that a disproportionate number of sex-mismatched donor/recipient pairs developed DCL; in fact, nearly all of our DCLs arose in the setting of a sex-matched pair. The apparent increased incidence in cord blood transplants, sex-mismatched donor/recipient pairs and ABO-mismatched transplants needs to be assessed in a large-scale registry using standard methodologies, which could help identify and define potential causes of DCL.Table 1:Patient Characteristics with Donor-Derived LeukemiaSexAge (years)Leukemia TypeTransplant TypeTime to Relapse (months)Sex MismatchABO MismatchChemotherapy PreparationM22ALLunrelated donor15NoYesalemtuzumabF1AMLrelated sibling14NoNoBu/Cy/Mito1M24AMLunrelated double-cord blood40NoNoTVTG2M20AMLunrelated donor5NoYesCy/TBI3M26AMLunrelated double-cord blood10.5YesYesFlu/Cy/TBI4M26ALLunrelated double-cord blood3.5NoYesFlu/Cy/TBI41. busulfan, cytarabine, mitoxantrone2. topotecan, vinorelbine, thiotepa, gemcitabine3. cyclophosphamide & total body irradiation4. fludarabine, cyclophosphamide & total body irradiation Disclosures:No relevant conflicts of interest to declare.

Transfusion strategies in patients undergoing stem-cell transplantation

Hemopoietic stem-cell transplant patients may require intensive blood component support. Complications of transfusions include transmission of viral and bacterial infections, transfusion-associated graft-versus-host disease and transfusion-related acute lung injury. Alloimmunization to red cell antigens may cause difficulties in selecting compatible blood, while alloimmunization to HLA expressed on platelets may cause subsequent platelet transfusion refractoriness. It is essential to define robust transfusion policies and procedures and these should be regularly audited. This article reviews blood component transfusion in the setting of hemopoietic stem-cell transplant and specifically discusses the management of ABO-mismatched transplants, the prevention of cytomegalovirus transmission, the prevention of transfusion-associated graft-versus-host disease and the use of granulocyte transfusions.

ABO Incompatibility is Associated with Increased Non-Relapse and GVHD Related Mortality in Patients with Malignancies Treated with a Reduced Intensity Regimen: A Single Center Experience of 221 Patients

The effect of ABO-incompatibility on transplantation outcome remains a controversial issue, with many of the reported studies showing conflicting results. In this study, we evaluate: the association between ABO-incompatibility and myeloid engraftment; the incidence and severity of acute and chronic graft-versus-host disease (GVHD); non-relapse mortality (NRM); GVHD-associated mortality, relapse and overall survival (OS). Our study includes 221 patients with malignant diseases treated in the same institution with the same reduced intensity regimen. Other variables known to affect the transplantation outcome such as age, disease, disease risk, and donor characteristics were well-balanced between ABO-matched and ABO-mismatched transplants. Analysis of our data shows increased incidence of NRM during the first months after transplantation in the groups of patients with major and minor ABO-incompatibility. Although neither incidence nor severity of GVHD differed significantly among the different groups, we found increased mortality associated with GVHD in the major ABO-incompatible groups. Long-term OS and relapse rate were not different, although we observed a trend for decreased OS during the first year post transplantation in the group of patients with major ABO-incompatibility. Our study showed that ABO-incompatibility has an adverse impact on the transplantation outcome.

317: Impact of Prophylactic Red Blood Cell Exchange for Prevention of Severe Immune Hemolysis in Pediatric Minor ABO-Mismatched Allogeneic Peripheral Blood Progenitor Cell Transplantation

The presence of minor ABO incompatibility between donor and recipient is common in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed severe immune hemolysis due to donor-derived passenger lymphocytes has been reported in minor and/or bidirectional ABO-mismatched transplants. To evaluate the impact of RBC exchange procedure in pediatric patients on the morbidity and outcome we analyzed 29 pediatric cases undergoing minor ABO-incompatible allo-HSCT from January 2000 to January 2007. First group (RBC exchange) included sixteen patients who underwent prophylactic red cell exchange. Six patients received grafts from HLA identical siblings, ten patients – from HLA matched unrelated donors. Eleven patients received bone marrow transplant (BMT), five patients received peripheral stem cell transplant (PBSC). Patient's age was 10 ± 5.3 years old.Second group (No – RBC exchange) included thirteen patients who did not undergo prophylactic red cell exchange, but the stem cell product was plasma depleted according to the institutional guidelines. Six patients received grafts from HLA identical siblings, three patients from HLA matched unrelated donors, and four patients form unrelated cord blood. Four patients received BMT, five patients received PBSC, four patients received cord blood transplant. Patient's age was 7.6 ± 5.4 years old.No incidence of immune mediated hemolysis was documented in both groups. No patients developed pure red cell aplasia. RBC engraftment was not different in both groups (23.2 ± 4.2 vs. 22 ± 4.2 days). Neutrophil engraftment was similar in both groups (21.0 ± 5.4 vs. 21.02 ± 4.0 days). No significant difference was found among the groups in the incidence of acute graft vs. host disease (GVHD). The incidence of chronic GVHD was insignificantly higher in patients with no RBC exchange (72% vs. 60%). The relapse rate and overall outcome were not influence.In conclusion these results suggest that RBC exchange does not have a significant impact in pediatric patients. Further investigations are required to identify the best clinical transfusion practice in pediatric patients with minor ABO incompatibility. The presence of minor ABO incompatibility between donor and recipient is common in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed severe immune hemolysis due to donor-derived passenger lymphocytes has been reported in minor and/or bidirectional ABO-mismatched transplants. To evaluate the impact of RBC exchange procedure in pediatric patients on the morbidity and outcome we analyzed 29 pediatric cases undergoing minor ABO-incompatible allo-HSCT from January 2000 to January 2007. First group (RBC exchange) included sixteen patients who underwent prophylactic red cell exchange. Six patients received grafts from HLA identical siblings, ten patients – from HLA matched unrelated donors. Eleven patients received bone marrow transplant (BMT), five patients received peripheral stem cell transplant (PBSC). Patient's age was 10 ± 5.3 years old. Second group (No – RBC exchange) included thirteen patients who did not undergo prophylactic red cell exchange, but the stem cell product was plasma depleted according to the institutional guidelines. Six patients received grafts from HLA identical siblings, three patients from HLA matched unrelated donors, and four patients form unrelated cord blood. Four patients received BMT, five patients received PBSC, four patients received cord blood transplant. Patient's age was 7.6 ± 5.4 years old. No incidence of immune mediated hemolysis was documented in both groups. No patients developed pure red cell aplasia. RBC engraftment was not different in both groups (23.2 ± 4.2 vs. 22 ± 4.2 days). Neutrophil engraftment was similar in both groups (21.0 ± 5.4 vs. 21.02 ± 4.0 days). No significant difference was found among the groups in the incidence of acute graft vs. host disease (GVHD). The incidence of chronic GVHD was insignificantly higher in patients with no RBC exchange (72% vs. 60%). The relapse rate and overall outcome were not influence. In conclusion these results suggest that RBC exchange does not have a significant impact in pediatric patients. Further investigations are required to identify the best clinical transfusion practice in pediatric patients with minor ABO incompatibility.

Prophylactic red blood cell exchange for prevention of severe immune hemolysis in minor ABO‐mismatched allogeneic peripheral blood progenitor cell transplantation after reduced‐intensity conditioning

Delayed severe immune hemolysis due to donor-derived passenger lymphocytes is observed in minor and/or bidirectional ABO-mismatched transplants, especially after reduced-intensity conditioning (RIC). The incidence is reported in up to 30 percent of patients and can result in multiorgan failure (MOF) and death. A first group of 32 patients (historical control) underwent RIC followed by allogeneic hematopoietic peripheral blood progenitor cell transplantation at our institution. In 5 of 10 patients with a minor and/or bidirectional ABO-mismatched graft, severe immune hemolysis was observed, leading to death in 3 of them. Therefore, we initiated a protocol with prophylactic red blood cell (RBC) exchange in minor and/or bidirectional ABO mismatch of a second group of patients (study group) and investigated the incidence of hemolysis, transplant-related mortality (TRM), and overall survival (OS) and compared these data with the historical control group. Twenty-two of 80 patients in the study group had a minor and/or bidirectional ABO-mismatched donor. In 20 patients, a prophylactic RBC exchange was performed. Three patients showed mild to moderate citrate reactions, and in 1 patient the procedure had to be stopped because of hypotension. Eighteen of 20 patients engrafted uneventfully, 1 patient rejected his graft, and another 1 showed signs of mild hemolysis. In the minor and/or bidirectional ABO-mismatched setting patients in the study group had a lower risk for TRM at 1 year compared to patients in the historical control group (16% vs. 53%, p < 0.05) and a better 1-year OS (65% vs. 40%, p < 0.05). RBC exchange is a safe procedure, reducing the incidence of delayed severe immune hemolysis and thus the risk of TRM in minor and/or bidirectional ABO-mismatched cases.

Impacts of ABO-Blood Type Incompatibility on Outcome of Unrelated Bone Marrow Transplantation through the Japan Marrow Donor Program.

ABO incompatibility between donor and recipient is not a barrier for successful allogeneic hematopoietic stem cell transplantation, but conflicting data still exist concerning its influence on transplant outcome, graft-versus-host disease (GVHD), relapse, and survival. We retrospectively analyzed the data of patients who underwent UR-BMT through the Japan Marrow Donor Program between January 1993 and September 2005, with complete data on ABO-blood group compatibility, age, and gender in donors and recipients.A total of 4,970 patients were transplanted with marrow from ABO-matched (M; n=2,513, 50.6%), major incompatible (MA; n=1,254, 25.2%), minor incompatible (MI; n=1,081, 21.8%), and bidirectional incompatible donors (IA; n=122, 2.5%), and were followed up over a median period of 325 days. Among these four groups, excluding age, there was no significant difference in the gender of patients and donors, number of transplantations, conditioning regimen, GVHD prophylaxis, and performance status before transplantation by the likelihood ratio test. The 5-year overall survival of any ABO-incompatible group was significantly lower compared to an identical group (Wilcoxon test, p<0.0001); the estimates for each group were 50.0% (M), 44.7% (MA), 46.7% (MI), and 41.3% (IA). Even in HLA-matched transplantation (n=2,608), a similar difference in overall survival was observed among the four groups (p=0.0124).In ABO-mismatched transplantation, the processing of bone marrow is necessary to prevent hemolysis of donor or recipient red blood cells as a result of the infusion of ABO-incompatible red blood cells or plasma contained within it. This procedure may reduce the number of hematopoietic stem cells. In fact, the mean number of total infused cells in each group was 3.10 (M), 1.52 (MA), 2.87 (MI), and 1.33 (IA) x108 per patient body weight (kg), with a significant difference in 4,210 patients in which data on the infused cell number were available (M; n=2,310, MA; n=996, MI; n=802, IA; n=102). To examine whether the difference in overall survival depended on the transplanted cell number, we used time-dependent Cox proportional hazards modeling to compare identical and major incompatible groups in terms of overall survival. Whereas the disease (standard and high-risk malignant disease, and benign disease; p=0.0000), patient age (p=0.0000), and ABO compatibility (p=0.0311) were elucidated to be significant risk factors, the number of infused cells was not (p=0.0603).Engraftment of red blood cells, white blood cells, and platelets were significantly delayed in major ABO mismatch in comparison with ABO identity (p<0.0001). Univariate analysis revealed a small but significant difference in the rate of grade III and IV GVHD among the four groups (p=0.0204). Patients with major and minor ABO incompatibility had a higher incidence of severe GVHD compared to ABO identity (21.9%, 20.4% vs 16.2%). There was no significant difference in GVHD of the skin and gut, but major and minor mismatch developed a higher incidence of moderate to severe hepatic GVHD compared to ABO match (p<0.0001, p=0.0010, respectively). ABO incompatibility had no significant effect on relapse, but the incidence of rejection was significantly higher with ABO-incompatible transplantation (p=0.0219).

Pre-transplant reduction of isohaemagglutinin titres by donor group plasma infusion does not reduce the incidence of pure red cell aplasia in major ABO-mismatched transplants

Major ABO incompatibility in stem cell transplant recipients has been associated with pure red cell aplasia (PRCA). Reduction of incompatible isohaemagglutinin titres pre-transplant by various methods has been thought to reduce the incidence of PRCA. Our data suggest that pre-transplant reduction of incompatible isohaemagglutinin titres by donor group plasma infusion does not reduce the incidence of PRCA. We also failed to find any relationship between pre-transplant ABO isohaemagglutinin titre and the risk of developing PRCA.