ABO-mismatched Hematopoietic Stem Cell Transplantation Research Articles

ABO Blood Grouping Mismatch in Hematopoietic Stem Cell Transplantation and Clinical Guides

Hematopoietic stem cell transplantation (HSCT) is a useful treatment. In contrast to solid organ transplantations, the use of ABO blood group mismatch is acceptable in HSCT. Immediate or late hemolytic reactions, pure red cell aplasia, delayed red blood cell recovery, and graft-versus -host disease are the results of this situation. This review shows the consequences of ABO-mismatched HSCT and its impacts on HSCT parameters, as well as providing clinical guides in this situation.

Pure Red Cell Aplasia in Major ABO-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Severe Pancytopenia

In major ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) persistence of antidonor isohemagglutinins leads to pure red cell aplasia (PRCA). To investigate severe pancytopenia noted in a previous study of PRCA, we analyzed all major ABO-mismatched HSCT between January 2003 and December 2012. Of 83 PRCA patients, 13 (16%) had severe pancytopenia. Severe pancytopenia was defined as an absolute neutrophil count (ANC) < 1.5 K/μL or requiring granulocyte colony-stimulating factor, platelets < 50 K/μL or transfusion dependent, and PRCA with RBC transfusion dependence at post-transplant day 90. In 6 patients (46%) severe pancytopenia resolved after PRCA resolution. Two patients (15%) received a second transplant because of persistent pancytopenia/secondary graft failure, 1 (8%) died from secondary graft failure despite a stem cell boost, 1 (8%) did not recover his platelet counts despite RBC/ANC recovery, and 3 patients (23%) died from disease relapse. We found that severe pancytopenia is frequently associated with PRCA in 16% of major ABO-incompatible HSCT with a higher incidence in males and pancytopenia resolved with resolution of PRCA in 46% of patients.

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.

Oral High Dose Dexamethasone for Pure Red Cell Aplasia Following ABO-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report.

Management of pure red cell aplasia following major ABO-mismatched hematopoietic stem cell transplantation is a therapeutic challenge. Various therapeutic modalities have been tried with variable responses, and patient remains transfusion dependent for a long time. We report here the use of pulsed oral high dose dexamethasone for pure red cell aplasia following ABO-mismatched allogeneic transplant with complete recovery.

Efficacy and Long-Term Outcome of Treatment for Pure Red Cell Aplasia after Allogeneic Stem Cell Transplantation from Major ABO-Incompatible Donors

No standard of care for pure red cell aplasia (PRCA) after major ABO-incompatible hematopoietic stem cell transplantation (HSCT) has been established. We conducted a retrospective cohort study to learn the efficacy and outcome of treatment for PRCA. One hundred forty-five recipients who showed delayed recovery of erythropoiesis and survived >100 days after transplantation without early disease progression were selected from 2846 records of major ABO-incompatible transplantation in the registry database in Japan, and detailed data of 46 recipients were collected. Treatment of PRCA, such as rapid tapering of calcineurin inhibitors, corticosteroids, or additional immunosuppressants, was given to 22 patients but not to the other 24 patients. The overall response rate of the treatment group was 54.5%. The number of days from diagnosis of PRCA to recovery of reticulocytes >1% and the cumulative number of red blood cell transfusions were not significantly different between the 2 groups. Infections accounted for the death of 7 of 11 patients in the treatment group. Univariate analysis identified 5 variables influencing survival, including graft-versus-host disease, disease progression, and treatment of PRCA; disease progression remained as the only factor negatively affecting survival by multivariate analysis. The present study could not provide supportive evidence for the beneficial effects of treatment for PRCA after major ABO-mismatched HSCT.

Impact of Donor-Recipient Major ABO Mismatch on Allogeneic Transplantation Outcome According to Stem Cell Source

Major ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT), even if it can be associated with several immunohematologic complications. Nevertheless, conflicting data still exist as to its influence on graft-versus-host disease (GVHD) incidence, relapse rate, and survival. To further investigate the relevance of ABO major mismatch on transplantation outcome, we retrospectively analyzed results from 414 patients with major or major/minor ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) allogeneic HSCT. Transplantation outcome was assessed by comparison with results from a 395-patient ABO-compatible population with similar characteristics. Median time to red cell transfusion independence was significantly longer in ABO-incompatible BM recipients (median time, 63 days vs 41 days; P =.001), with faster disappearance of antidonor IgM hemagglutinins in unrelated recipients (median time, 36 days vs 44 days; P = .03) and in patients with grade > or =II acute GVHD (aGVHD) (median time, 35 days vs 59 days ; P = .001). In PB stem cell (PBSC) and CB transplantation, erythroid reconstitution was not significantly delayed, regardless of donor type or presence of aGVHD. A slight correlation between ABO incompatibility and GVHD incidence was found in PBSC recipients when considering grade > or =II aGVHD incidence (63% in ABO-matched HSCT vs 83% in ABO-mismatched HSCT; P = .055), but this was not confirmed in multivariate analysis. In patients with acute leukemia, multivariate analysis revealed an association between major ABO mismatch and decreased relapse rate with borderline statistical significance (hazard ratio, 0.65; P = .04). Major ABO incompatibility mainly, if not exclusively, affects red blood cell engraftment after BM transplantation. Somewhat surprisingly, the graft-versus-plasma cell effect seems to be confined to this stem cell source.

Impact of ABO-Incompatible Donor on Early and Late Outcome of Hematopoietic Stem Cell Transplantation

ABO incompatibility is not a barrier to allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of an ABO mismatch on the outcome of the HSCT remains controversial. We analyzed whether ABO incompatibility leads to an increased risk of early/late complications, mortality, or increased transfusion requirements. The 147 consecutive allogeneic HSCTs includes 80 ABO-identical and 25 major, 30 minor, and 12 bidirectional ABO-mismatched grafts. The four groups were balanced with respect to disease status at transplantation. Transplantation-related mortality was significantly greater ( P < .01) and overall survival significantly shorter ( P = 0.2) among HSCT recipients with minor ABO-mismatched grafts. The relapse rate, progression-free survival, and transfusion requirements until discharge were not different between ABO-identical and ABO-mismatched groups. Pure red cell aplasia (PRCA); ( P < .0001) and delayed red blood cell (RBC) engraftment ( P < .001) were more frequent in HSCT recipients with major mismatched donors. Delayed RBC engraftment was associated with posttransplantation hyperferritininemia and increased mortality risk ( P = .05). The greater frequency of sinusoidal obstruction syndrome and graft-versus-host disease (GVHD) in patients with minor mismatched transplants, did not show statistical significance. In contrast severe GVHD was significantly more frequent among minor mismatched patients ( P = .04). ABO-mismatched HSCT might have an unfavorable impact on transplant outcomes. Selection of ABO-compatible donors when possible, strategies to prevent and treat PRCA, modifications in transfusion practice, and effective iron chelation are among the measures that can improve transplant outcomes.

Mesenchymal stem cells for the treatment of refractory pure red cell aplasia after major ABO-incompatible hematopoietic stem cell transplantation

Pure red cell aplasia (PRCA) is a well-known, although infrequent, hematological complication after allogeneic hematopoietic stem cell transplantation (HSCT). PRCA occurs in cases of major ABO mismatch between donor and recipient and is believed to be due to inhibition of donor erythroid progenitors by residual host isohemagglutinins. The purpose of our study was to further evaluate the efficacy of human adipose tissue-derived mesenchymal stem cells (AMSC) as the salvage therapy for refractory PRCA after major ABO-incompatible HSCT. Two patients with refractory pure red cell aplasia received intravenous infusions of AMSC at a dose of 1.5 x 10(6)/kg of the patients' weight, and rapid recovery from PRCA without any side effects was observed. We conclude that AMSC seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.