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Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts.
Transplant Cell Ther. 2021 08; 27(8):697.e1-697.e5.TC

Abstract

As a result of the COVID-19 pandemic, most centers performing allogeneic hematopoietic cell transplantation (allo-HCT) have switched to the use of cryopreserved grafts. Previous investigators have suggested that cryopreserved allografts may heighten risk of nonengraftment. To date, no study has investigated the effect of cryopreservation of CD34-selected hematopoietic progenitor cells (CD34+ HPCs) used as the sole graft source. In this study, we sought to evaluate outcomes after unrelated donor or matched sibling allo-HCT with cryopreserved CD34+ HPCs. This was a single-center analysis of adult patients with hematologic malignancies who underwent allo-HCT with cryopreserved CD34-selected allo-HCT grafts between January 2010 and June 2017. All patients received ablative conditioning and antirejection prophylaxis with rabbit antithymocyte globulin. G-CSF-mobilized leukapheresis products underwent CD34 selection using the CliniMACS Reagent System. Cells were then cryopreserved in DMSO (final concentration 7.5%) to -90 °C using a controlled-rate freezing system before being transferred to vapor-phase liquid nitrogen storage. In internal validation, this method has shown 92% mean CD34+ cell viability and 99.7% mean CD34+ cell recovery. Engraftment was defined as the first of 3 consecutive days of an absolute neutrophil count of ≥0.5. Platelet recovery was recorded as the first of 7 consecutive days with a platelet count ≥20 K/μL without transfusion. Kaplan-Meier methodology was used to estimate overall survival (OS) and relapse-free survival (RFS), and cumulative incidence functions were used to estimate rates of relapse, nonrelapse mortality (NRM), and acute graft-versus-host disease (GVHD). A total of 64 patients received a cryopreserved CD34-selected graft. The median CD34+ cell count before cryopreservation was 6.6 × 106/kg (range, 1.4 to 16.1 × 106/kg), and the median CD3+ cell count was 2.0 × 103/kg (range, 0 to 21.1 × 106/kg). All patients were engrafted, at a median of 11 days post-HCT (range, 8 to 14 days). One patient had poor graft function in the setting of cytomegalovirus viremia, necessitating a CD34-selected boost on day +57. The median time to platelet recovery was 16 days (range, 13 to 99 days). The estimated 2-year OS was 70% (95% confidence interval [CI], 58% to 83%) with cryopreserved grafts versus 62% (95% CI, 57% to 67%) with fresh grafts (hazard ratio [HR], 0.86; 95% CI, 0.54 to 1.35; P = .5). The estimated 2-year RFS in the 2 groups was 59% (95% CI, 48% to 74%) versus 56% (95% CI, 51% to 61%; HR, 1.01; 95% CI, 0.68 to 1.51; P > .9). The cumulative incidence of relapse at 2 years was 29% (95% CI, 17% to 41%) versus 23% (95% CI, 19% to 27%; P = .16), and the cumulative incidence of NRM at 2 years was 17% (95% CI, 9% to 28%) versus 23% (95% CI, 19% to 28%; P = .24). The cumulative incidence of grade II-IV acute GVHD by day +100 was 16% with cryopreserved grafts (95% CI, 8% to 26%) and 16% (95% CI, 13% to 20%; P = .97) with fresh grafts. Moderate to severe chronic GVHD by day +365 occurred in only 1 recipient of a cryopreserved graft (2%). Our data show that in patients with hematologic malignancies who received cryopreserved allogeneic CD34+ HPCs, engraftment, GVHD, and survival outcomes were consistent with those seen in recipients of fresh allogeneic CD34+ HPC grafts at our center. Our laboratory validation and clinical experience demonstrate the safety of our cryopreservation procedure for CD34-selected allografts.

Authors+Show Affiliations

Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: jacobr@mskcc.org.Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York; Department of Medicine, Leukemia Service, Memorial Sloan Kettering, Cancer Center, New York, New York.Department of Medicine, Weill Cornell Medical College, New York, New York; Pediatric Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33991721

Citation

Jacob, Reuben P., et al. "Universal Engraftment After Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts." Transplantation and Cellular Therapy, vol. 27, no. 8, 2021, pp. 697.e1-697.e5.
Jacob RP, Flynn J, Devlin SM, et al. Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts. Transplant Cell Ther. 2021;27(8):697.e1-697.e5.
Jacob, R. P., Flynn, J., Devlin, S. M., Maloy, M., Giralt, S. A., Maslak, P., O'Reilly, R. J., Tonon, J. A., Perales, M. A., Avecilla, S. T., & Cho, C. (2021). Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts. Transplantation and Cellular Therapy, 27(8), e1-e5. https://doi.org/10.1016/j.jtct.2021.04.026
Jacob RP, et al. Universal Engraftment After Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts. Transplant Cell Ther. 2021;27(8):697.e1-697.e5. PubMed PMID: 33991721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts. AU - Jacob,Reuben P, AU - Flynn,Jessica, AU - Devlin,Sean M, AU - Maloy,Molly, AU - Giralt,Sergio A, AU - Maslak,Peter, AU - O'Reilly,Richard J, AU - Tonon,Jo-Ann, AU - Perales,Miguel Angel, AU - Avecilla,Scott T, AU - Cho,Christina, Y1 - 2021/05/13/ PY - 2021/02/26/received PY - 2021/04/26/revised PY - 2021/04/29/accepted PY - 2022/08/01/pmc-release PY - 2021/5/16/pubmed PY - 2021/7/30/medline PY - 2021/5/15/entrez KW - Allogeneic hematopoietic stem cell transplantation KW - CD34 selection KW - COVID-19 KW - Cryopreservation KW - Engraftment SP - 697.e1 EP - 697.e5 JF - Transplantation and cellular therapy JO - Transplant Cell Ther VL - 27 IS - 8 N2 - As a result of the COVID-19 pandemic, most centers performing allogeneic hematopoietic cell transplantation (allo-HCT) have switched to the use of cryopreserved grafts. Previous investigators have suggested that cryopreserved allografts may heighten risk of nonengraftment. To date, no study has investigated the effect of cryopreservation of CD34-selected hematopoietic progenitor cells (CD34+ HPCs) used as the sole graft source. In this study, we sought to evaluate outcomes after unrelated donor or matched sibling allo-HCT with cryopreserved CD34+ HPCs. This was a single-center analysis of adult patients with hematologic malignancies who underwent allo-HCT with cryopreserved CD34-selected allo-HCT grafts between January 2010 and June 2017. All patients received ablative conditioning and antirejection prophylaxis with rabbit antithymocyte globulin. G-CSF-mobilized leukapheresis products underwent CD34 selection using the CliniMACS Reagent System. Cells were then cryopreserved in DMSO (final concentration 7.5%) to -90 °C using a controlled-rate freezing system before being transferred to vapor-phase liquid nitrogen storage. In internal validation, this method has shown 92% mean CD34+ cell viability and 99.7% mean CD34+ cell recovery. Engraftment was defined as the first of 3 consecutive days of an absolute neutrophil count of ≥0.5. Platelet recovery was recorded as the first of 7 consecutive days with a platelet count ≥20 K/μL without transfusion. Kaplan-Meier methodology was used to estimate overall survival (OS) and relapse-free survival (RFS), and cumulative incidence functions were used to estimate rates of relapse, nonrelapse mortality (NRM), and acute graft-versus-host disease (GVHD). A total of 64 patients received a cryopreserved CD34-selected graft. The median CD34+ cell count before cryopreservation was 6.6 × 106/kg (range, 1.4 to 16.1 × 106/kg), and the median CD3+ cell count was 2.0 × 103/kg (range, 0 to 21.1 × 106/kg). All patients were engrafted, at a median of 11 days post-HCT (range, 8 to 14 days). One patient had poor graft function in the setting of cytomegalovirus viremia, necessitating a CD34-selected boost on day +57. The median time to platelet recovery was 16 days (range, 13 to 99 days). The estimated 2-year OS was 70% (95% confidence interval [CI], 58% to 83%) with cryopreserved grafts versus 62% (95% CI, 57% to 67%) with fresh grafts (hazard ratio [HR], 0.86; 95% CI, 0.54 to 1.35; P = .5). The estimated 2-year RFS in the 2 groups was 59% (95% CI, 48% to 74%) versus 56% (95% CI, 51% to 61%; HR, 1.01; 95% CI, 0.68 to 1.51; P > .9). The cumulative incidence of relapse at 2 years was 29% (95% CI, 17% to 41%) versus 23% (95% CI, 19% to 27%; P = .16), and the cumulative incidence of NRM at 2 years was 17% (95% CI, 9% to 28%) versus 23% (95% CI, 19% to 28%; P = .24). The cumulative incidence of grade II-IV acute GVHD by day +100 was 16% with cryopreserved grafts (95% CI, 8% to 26%) and 16% (95% CI, 13% to 20%; P = .97) with fresh grafts. Moderate to severe chronic GVHD by day +365 occurred in only 1 recipient of a cryopreserved graft (2%). Our data show that in patients with hematologic malignancies who received cryopreserved allogeneic CD34+ HPCs, engraftment, GVHD, and survival outcomes were consistent with those seen in recipients of fresh allogeneic CD34+ HPC grafts at our center. Our laboratory validation and clinical experience demonstrate the safety of our cryopreservation procedure for CD34-selected allografts. SN - 2666-6367 UR - https://www.unboundmedicine.com/medline/citation/33991721/Universal_Engraftment_after_Allogeneic_Hematopoietic_Cell_Transplantation_Using_Cryopreserved_CD34_Selected_Grafts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2666-6367(21)00887-3 DB - PRIME DP - Unbound Medicine ER -