Major ABO-incompatible Allogeneic Hematopoietic Stem Research Articles

Prevalence of Pure Red Cell Aplasia Following Major ABO-Incompatible Hematopoietic Stem Cell Transplantation.

BackgroundPure red cell aplasia (PRCA) is one of the important complications in major ABO-incompatible allogeneic hematopoietic stem cell transplantation (HSCT). The established pathogenic factor of PRCA is the persistence of high anti-donor isohemagglutinins. As previously verified, the conditioning regimen and donor type were the factors associated with the development of PRCA in the small-sized studies. Currently, the prevalence, risk factors, and prognosis of PRCA are still worth studying to provide evidence.MethodsWe conducted a prospective nested case-control study to determine the prevalence, donor-related factors, and the outcomes of PRCA following major ABO-incompatible transplantation. A total of 469 patients who underwent ABO-incompatible grafts were observed.ResultsNone of the patients were diagnosed with PRCA with minor or bidirectional ABO-incompatible HSCT. Thirteen of the187 patients (7%; 95% confidence interval [CI], 3.9%–11.9%) developed PRCA following major ABO-incompatible HSCT. Eleven of the 13 patients with PRCA recovered entirely. Donor type was an independent factor associated with post-HSCT PRCA (odds ratio [OR]=0.030; 95% CI, 0.003–0.321; P=0.004). The cumulative incidence rates of post-HSCT PRCA in the context of major ABO-incompatible HSCT were 0.8%, 13.1%, and 27.2% for the haploidentical donor (HID), unrelated donor, and matched related donor, respectively. No significant influence of PRCA on transplantation outcomes was observed.In conclusion, post-HSCT PRCA is a rare and less threatening complication in major ABO-incompatible HSCT. The majority of patients with PRCA could recover. Additionally, HIDs for recipients may have a low risk of post-HSCT PRCA. This trial was registered at www.chictr.org.cn (#ChiCTR2000041412).

Recent progress in the diagnosis and management of acquired pure red cell aplasia

Acquired pure red cell aplasia (PRCA) is characterized by normocytic anemia, reticulocytopenia, and a marked decrease in erythroid cell count in the bone marrow. PRCA develops in the context of various backgrounds, including recently recognized immune checkpoint inhibitor-associated PRCA, that need careful differential diagnoses. Besides humoral abnormalities such as major ABO-incompatible allogeneic hematopoietic stem cell transplantation-related PRCA, dysregulations of T cells have been shown. STAT3 gene mutations of cytotoxic T cells were identified in 40% of PRCA patients, which might suggest their use as novel molecular markers for PRCA. As initial management options for PRCA, red blood cell transfusion and immunosuppressive therapy (IST) drugs, such as cyclosporin, are usually selected. Roughly 80% of patients respond to IST; however, some relapse afterward or are refractory to IST. When patients with PRCA become refractory to two or three lines of IST, allogeneic hematopoietic stem cell transplantation (HCT) would become an appropriate choice, although the optimal procedures for allogeneic HCT have not been determined. A prospective study of PRCA in Japan has been ongoing since 2016 to solve the myriad clinical issues of PRCA.

Donor-type fresh frozen plasma is effective in preventing hemolytic reaction in major ABO incompatible allogeneic stem cell transplant.

Hemolysis at the time of graft infusion is one of the immediate complications in major ABO-incompatible allogeneic hematopoietic stem cell transplants (HSCTs). We conducted a retrospective analysis to evaluate the efficacy of donor-type fresh frozen plasma (FFP) in reducing isohemagglutinin titer and preventing hemolysis, as well as its effect on delayed red cell engraftment. This is a single-center study on a series of 380 allogeneic HSCT between 2005 and 2015; of which 99 were either major (n = 74) or bidirectional (n = 25) ABO mismatched. Pre-transplant infusion of FFP, post-transplant complications and transfusion requirements were determined by retrospective review of individual medical records. Laboratory results were also reviewed for evidence of hemolysis and pure red cell aplasia (PRCA). Clinical manifestation of hemolysis attributable to ABO mismatch was present in one recipient of major ABO-incompatible peripheral blood stem cell (PBSC) with a titer of 64. Another recipient of major ABO-incompatible PBSC with a titer of 64 showed biochemical evidence of hemolysis. Both patients recovered with supportive treatment. Hemolysis did not occur in any patients with titer of 32 or less at the time of stem cell infusion. We were unable to demonstrate the influence of any variables on the incidence of PRCA. Our experience demonstrated that donor-type FFP is safe and effective in preventing acute hemolysis in major ABO-mismatched HSCT. We have also established the titer of 64 as the threshold that may cause hemolysis and therefore efforts should be made to reduce titer to below this level.

Successful Treatment of Pure Red Cell Aplasia after Major ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with Repeated Doses of the Single-Agent Rituximab: A Case Report.

Background: ABO incompatibility occurs in up to 20–40% of HLA matched allogeneic hematopoietic stem cell transplantation (HSCT). Pure red cell aplasia (PRCA) following ABO-incompatible allogeneic HSCT is a rare complication associated with interaction of recipient anti-A or anti-B isoagglutinins, produced by residual B cells, with donor erythrocytes precursors expressing A and/or B antigens. The best treatment approach for PRCA is not established. Plasma exchange and immunoadsorption are regarded as a first-line treatment strategies. Other therapeutic approaches include: erythropoietn (EPO), donor-derived leukocyte infusion (DLI), steroids or induction of graft versus host disease (GVHD) by immunosuppression withdraw. Moreover, recovery or erythropoiesis is often incomplete and may induce futher complications. Recent reports describe successful treatment of PRCA and others cytopenias after HSCT using Rituximab (Mabthera®; Roche; Switzerland). This drug is a chimeric IgG1 monoclonal antibody directed against the CD20 surface antigen expressed by most human B lymphocytes. Its exact mechanism of action is not known.Case Report: We treat a 47-year-old woman with PRCA after a major ABO-mismatched (Donor A Rh-; Recipient O Rh-) allogeneic HSCT after a second remission of a acute myeloid leukemia. Allogeneic HSCT was performed in November 2005, from a HLA-matched older sister, using bone marrow graft (Mn cell dose 1,72x108/kg) following a myeloablative conditioning with busulfan (16mg/kg) and melfalan (140mg/m2). GVHD prophylaxis included cyclosporine A and methotrexate. Baseline anti-A isoagglutinin IgM titers of the paient before transplantation was 1:128 and after immunoadsorption with plasma A for 48 hours decreased to 1:32. One plasmapheresis session was performed to remove ABO antibodies from the patient and her anti-A IgM titer dropped to 1:4 before bone marrow infusion. We also removed red blood cells from the donor's marrow product to prevent risk of hemolysis. After bone marrow transplantation, the patient developed a severe anemia that required weekly red blood cells transfusion over six months. Reticulocyte counts were extremely low during this period, bone marrow aspirate was normal, except for decreased erythrocyte precursors (only 1% of total cells). In August 2006, the diagnosis of PRCA was set after exclusion of red blood cells alloantibodies, hemolysis and viral or bacterial infection. Donor chimerism (STR) was totally completed and the recipient anti-A IgM titer was 1:16 and the patient showed no evidence of GVHD. In October 2006, she was treated with rituximab 375mg/m2 administered once weekly for four weeks. In the next two months, after the treatment with rituximab, her hemoglobin (Hb) increased from 5.5g/dl to 12g/dl. Up to her last medical avaluation (July 2006), she was in PRCA remission, her Hb was 12g/dl and she had no detectable anti-A titer. Conclusion: Rituximab can be a very effective treatment to PRCA secondary to major ABO-incompatible allogeneic stem cell transplantation. The best dose schedule and long term effects must be establish.

Clinical features and risk factors of pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group a/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.

Clinical Features and Risk Factors of Pure Red Cell Aplasia Following Major ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation.

Objective:To study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT).Method:We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April, 1997 to December, 2005.Results:1. 11 out of the 42 patients developed PRCA (26.1%); 2. All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n=9) or blood group B donor (n=2). 3. The following factors were associated with an increased risk of PRCA:(1) blood group O recipient;(2) blood group A donor;(3) blood group O/A in recipient/donor pair;4. Only blood group O/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis (P=0.006); 5. 6 patients who received donor-type plasma exchange did not develop PRCA, and among them, 5 cases were the O blood group recipients. 8 patients obtained spontaneous remission and in the remaining 3 patients, 2 patients with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA.Conclusions:The incidence of PRCA in this series of patients was 26.1%. Only blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange is an effective approach for the treatment and prophylaxis of PRCA. Anti-CD20 monoclonal antibody is indicated for patients who are not response to conventional therapy.