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Iron Overload is Associated with Delayed Engraftment and Increased Non-Relapse Mortality in Recipients of Umbilical Cord Blood Hematopoietic Cell Transplantation
Malki, M. M. A., Song, J. Y., Yang, D., Cao, T., Aldoss, I., Mokhtari, S., Dadwal, S., Marcucci, G., Karanes, C., Snyder, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
The negative impact of Iron overload (IO) on outcomes of allogeneic hematopoietic cell transplantation (HCT) is well-recognized, but its impact on umbilical cord blood (UCB) transplant outcome is unknown. We retrospectively analyzed outcomes of 150 patients who received UCB-HCT at our institution, stratified by pre-HCT serum ferritin level (SF) of 2000 ng/ml. Two-year overall survival rate among patients with SF >2000 and ≤2000 ng/ml was 26.1% (95%CI: 10.6%-44.7%) and 52.1% (95%CI: 40.1%-62.8%), respectively; HR=2.26 (95%CI: 1.28-4.00, P=0.005). Two-year non-relapse mortality rate was higher among patients with SF >2000 ng/ml (56.5%, 95%CI: 33.3%-74.4%) compared to SF ≤2000 ng/ml (30.1%, 95%CI: 20.0%-40.9%); HR=2.18, (95%CI: 1.10-4.31, P=0.025). Neutrophil engraftment at 42 days was 78.3% (95%CI: 53.5%-90.8%) in patients with SF >2000 ng/ml, versus 91.8% (95%CI: 82.1%-96.4%) in patients with SF ≤2000 ng/ml; HR=0.58 (95%CI: 0.35-0.96, P=0.034). A significant difference in platelet engraftment at 3 months was also observed: 52.2% (95%CI: 29.4%-70.8%) for SF>2000 ng/ml versus 80.8% (95%CI: 69.5%-88.3%) for SF ≤2000 ng/ml; HR=0.48 (95%CI: 0.23-0.98, P=0.044). In conclusion, IO defined by SF of 2000 ng/ml is a strong adverse prognostic factor for UCB-HCT and should be a considered when UCB is chosen as the graft source for patients without a fully matched donor.
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Prevention of transfusion-transmitted cytomegalovirus infection using leukoreduced blood components in patients receiving seronegative umbilical cord blood transplantation
Shigemura, T., Yanagisawa, R., Komori, K., Morita, D., Kurata, T., Tanaka, M., Sakashita, K., Nakazawa, Y.
Transfusion. 2019
Abstract
BACKGROUND Leukoreduced blood components have been widely implemented to prevent transfusion-transmitted cytomegalovirus (TT-CMV) in transplantation. Recent progress in leukoreduction technology has helped reduce the risk of TT-CMV in hematopoietic stem cell transplantation; however, its efficacy in umbilical cord blood transplantation (CBT) has not been systematically studied. STUDY DESIGN AND METHODS We retrospectively analyzed the incidence of CMV infection in patients treated with CBT who received prestorage leukoreduced, CMV-unselected blood components between 2007 and 2017 in a single Japanese pediatric center. Patients were monitored for CMV antigenemia at least once weekly. RESULTS In total, 71 patients treated with CBT were identified. Two patients were excluded because of unknown CMV serostatus or early death after CBT. Of the remaining 69 patients, 24 developed CMV antigenemia. Among them, 3 received granulocyte transfusions (3 of 3; 100%), 2 were infants with severe combined immunodeficiency who had been infected with CMV before CBT (2 of 2; 100%), and 19 were CMV-seropositive patients (19 of 23, 82.6%). Conversely, of the remaining 45 patients in whom CMV antigenemia did not develop, 41 were seronegative (0 of 41; 0%) and were transfused with a total of 925 leukoreduced, CMV-unselected blood components. Among the 41 patients, 9 (22%) received in vivo T-cell depletion with antithymocyte globulin. None of the patients in the seronegative group has subsequently shown evidence of CMV infection or developed CMV disease. CONCLUSION Using prestorage leukoreduction, no cases of CMV infection were detected in seronegative CBT patients. Our findings showed the safety of leukoreduction in preventing TT-CMV in this patient group.
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Results of two protocols for platelet transfusion in patients undergoing abo incompatible hematopoietic stem cell transplantation
Solves, P., Diaz, A., Carretero, C., Gomez, I., Carpio, N., Sanz, G.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2019
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Comparison of transfusion requirements in adult patients undergoing haploidentical or single unit umbilical cord blood stem cell transplantation
Solves, P., Sanz, J., Gomez, I., de la Puerta, R., Arnao, M., Montoro, J., Pinana, J. L., Carretero, C., Balaguer, A., Guerreiro, M., et al
European journal of haematology. 2019
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Editor's Choice
Abstract
OBJECTIVES Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) modalities have been developed to offset the lack of matched donors. In this study we compare the transfusion requirements of patients undergoing UCBT and Haplo-HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. METHODS The study reviewed 67 and 46 patients undergoing UCBT and Haplo-HSCT, respectively. RESULTS There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median Time to RBC transfusion independence was 35 days and 25.5 days in patients who received an UCBT and Haplo-HSCT, respectively (P=0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for Haplo-HSCT patients (P< 0.001). Days until neutrophils > 0.5 x 10(9) /L was the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and Haplo-HSCT. CONCLUSIONS Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Patients undergoing allogeneic transplantation from different donor sources had their transfusion requirements monitored.
Intervention
Umbilical cord blood transplantation (n=67)
Comparison
Haploidentical transplantation (n=46)
Outcome
There were no significant differences for RBC and PLT requirements according to the transplantation modality. Days until neutrophils > 0.5 x 10(9) /L was the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and Haplo-HSCT.
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Red blood cell transfusion burden by day 30 predicts mortality in adults after single-unit cord blood transplantation
Konuma, T., Oiwa-Monna, M., Mizusawa, M., Isobe, M., Kato, S., Nagamura-Inoue, T., Takahashi, S., Tojo, A.
Bone marrow transplantation. 2019
Abstract
Increased red blood cell (RBC) transfusion requirements are associated with morbidity and mortality after allogeneic hematopoietic cell transplantation. However, its impact on the outcomes after cord blood transplantation (CBT) is unclear. We retrospectively analyzed the data of 278 adult patients who received single-unit CBT in our institute. The median number of RBC transfusions for each patient was 12 units (range, 4-66) by day 30 and 14 units (range, 4-70) by RBC engraftment. Sex, cord blood CD34(+) cell dose, cytomegalovirus serostatus, total body irradiation dose in the conditioning regimen, ABO blood group incompatibility, and pre-CBT RBC transfusion requirements were significantly associated with the number of RBC transfusion units in the linear regression analysis. In the multivariate analysis, RBC transfusion ≥18 units by day 30 was significantly associated with higher overall mortality (hazard ratio, 1.86; P = 0.018). These data suggested that early RBC transfusion burden was significantly associated with overall mortality in adult patients undergoing single CBT. Early RBC transfusion burden might be a surrogate marker for poor outcomes after single CBT.
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Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes
Tanoue, S., Konuma, T., Kato, S., Oiwa-Monna, M., Isobe, M., Jimbo, K., Takahashi, S., Tojo, A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Platelet transfusion refractoriness (PTR) is frequently observed after allogeneic hematopoietic cell transplantation (HCT). However, the incidence of and risk factors for PTR, and impact of PTR on transplant outcomes after cord blood transplantation (CBT) have not been fully investigated. We retrospectively analyzed 185 adult patients who received single-unit CBT in our institute. The mean 16-hour corrected count increment (CCI) for the 5,840 platelet transfusions was 3.68x10(9)/l. Among them, 3,196 transfusions (54.7%) were associated with a PTR with 16-hour-CCI <4.5x10(9)/l. Results of multivariate analysis indicated that the following factors were significantly associated with decreased platelet transfusion responses: female sex with pregnancy history, male sex, the presence of HLA class I antibody, lower cord blood total nucleated cell dose, lower cord blood CD34+ cell dose, 3 locus HLA disparities, body temperature ≥38 degrees C, CRP ≥10mg/dl, cytomegalovirus reactivation, use of foscarnet, and use of liposomal amphotericin B. By contrast, GVHD prophylaxis including methotrexate, ABO minor mismatch, use of ganciclovir, and use of linezolid were significantly associated with better platelet transfusion responses. PTR had a significant effect on poor neutrophil and platelet recovery, and overall mortality after CBT. These data suggest that early phase PTR may be predictive of engraftment and mortality after single-unit CBT for adults.