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Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria
Nakamura, Y., Takenaka, K., Yamazaki, H., Onishi, Y., Ozawa, Y., Ikegame, K., Matsuoka, K. I., Toubai, T., Ueda, Y., Kanda, Y., et al
International Journal of Hematology. 2021;113(1):122-127
Abstract
The safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) remain unclear. Therefore, we retrospectively analyzed the outcomes of 42 adult patients with PNH who underwent allogeneic HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median patient age was 32.5 years. The number of packed red cell (PRC) transfusions was < 20 times in 19 patients and ≥ 20 times in 16; 7 patients had missing data. Stem cell sources were bone marrow (N = 15) or peripheral blood (N = 13) from a related donor or bone marrow (N = 11) and cord blood (N = 3) from an unrelated donor. The cumulative incidence of neutrophil engraftment at day 40 was 81%. Six patients died before engraftment, and the 6-year overall survival (OS) was 74%. The OS of patients with < 20 pretransplant PRC transfusions was significantly higher than that of patients with ≥ 20 pretransplant PRC transfusions (95% vs. 63%; P < 0.05). Moreover, the OS of patients aged < 30 years was significantly higher than that of patients aged ≥ 30 years (90% vs. 59%; P < 0.05). Allogeneic HSCT for PNH could provide favorable survival; however, pretransplant transfusion burden and patient age should be considered when deciding the timing of allogeneic HSCT.
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Transfusions in aplastic anemia patients cause HLA alloimmunization Comparisons of current and past cohorts demonstrate progress
Julen, K., Volken, T., Holbro, A., Infanti, L., Halter, J. P., Schaub, S., Wehmeier, C., Diesch, T., Rovó, A., Passweg, J. R., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Transfusions are the mainstay of supportive therapy in patients with aplastic anemia (AA) and may lead to anti-human leukocyte antigen (HLA) alloimmunization, thereby also increasing the risk for donor-specific antibodies in the setting of HLA-mismatched transplantation. Historically, AA patients were thought to be at particularly high risk for HLA alloimmunization. OBJECTIVE In the past decades, blood product manufacturing (leukoreduction), but also HLA antibody testing has improved significantly by single antigen bead (SAB) technology. It is currently unknown how those developments have impacted HLA-alloimmunization and treatment outcome in patients with AA. STUDY DESIGN We retrospectively investigated 54 AA patients treated by immunosuppressive therapy and/or allogeneic hematopoietic cell transplantation after the introduction of the SAB assay at our center. We compared the HLA antibody results to a historical AA cohort (n=26), treated prior to introduction of leukoreduced blood products from 1975 to 1995. RESULTS HLA alloimmunization was detected in 43 of 54 (80%) patients in recently treated patient. Past pregnancy, female gender, disease severity, age and a history of more transfusions were significantly associated with a larger number and/or higher intensity (mean fluorescence intensity) of HLA antibodies. Treatment outcome including bleeding episodes, response to treatment, engraftment, GvHD and overall survival was not associated with HLA alloimmunization. In the historical cohort a significantly higher number of HLA antibodies (p<0.01) with a higher MFI (p<0.01) was observed. CONCLUSION HLA alloimmunization remains frequent in AA tested by current techniques but it has significantly decreased since prior decades and does not affect treatment outcome.
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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
Mehta, P., Ramprakash, S., Raghuram, C. P., Trivedi, D., Dhanya, R., Agarwal, R. K., Faulkner, L.
Annals of hematology. 2021
Abstract
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.
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Blood transfusion support for sickle cell patients during haematopoietic stem cell transplantation: a single-institution experience
De Santis, G. C., Costa, T. C. M., Santos, F. L. S., da Silva-Pinto, A. C., Stracieri, Abpl, Pieroni, F., Darrigo-Junior, L. G., de Faria, J. T. B., Grecco, C. E. S., de Moraes, D. A., et al
British journal of haematology. 2020
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A prospective non-interventional study on the impact of transfusion burden and related iron toxicity on outcome in myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation()
Cremers, E. M. P., de Witte, T., de Wreede, L., Eikema, D. J., Koster, L., van Biezen, A., Finke, J., Socie, G., Beelen, D., Maertens, J., et al
Leukemia & lymphoma. 2019;:1-10
Abstract
Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.