Day 4 collection of granulocyte colony-stimulating factor-mobilized HLA-matched sibling donor peripheral blood allografts demonstrates no long-term increase in chronic graft-versus-host disease or relapse rates |
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| Institution: | 1. Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA;2. Biostatistics Shared Resources, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA;1. Gastroenterology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi and University of Verona, Verona, Italy;2. Division of Surgery and Cell Therapy Unit, Institute for Health Research, Jiménez Díaz Foundation University Hospital, Madrid, Spain;3. Laboratory of Advanced Cellular Therapies, Hematology Unit, Vicenza Hospital, Vicenza, Italy;1. Universidad San Francisco de Quito USFQ, Colegio de Ciencias de la Salud, Escuela de Medicina, Quito, Ecuador;2. Universidad San Francisco de Quito USFQ, Instituto de Investigaciones en Biomedicina iBioMed, Quito, Ecuador;3. Mito-Act Research Consortium, Quito, Ecuador;4. Sistemas Médicos SIME, Universidad San Francisco de Quito USFQ, Quito, Ecuador;5. Biología, Colegio de Ciencias Biológicas y Ambientales COCIBA, Universidad San Francisco de Quito USFQ, Quito, Ecuador;6. Instituto de investigaciones biotecnológicas IIB, Universidad Nacional de San Martín, Buenos Aires, Argentina;7. School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;8. Instituto de Neurociencias, Universidad San Francisco de Quito USFQ, Quito, Ecuador;9. Fundação Oswaldo Cruz, FIOCRUZ Instituto Oswaldo Cruz (IOC), Rio de Janeiro, Brazil;1. Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand;2. Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand;3. Chulalongkorn Comprehensive Cancer Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand;4. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand;5. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan;6. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan;7. Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;8. Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;;2. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;;3. Institute of Hematology, Zhejiang University, Hangzhou, China;;4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China;5. Shanghai YaKe Biotechnology Ltd.;6. Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;1. Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA;2. Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA;3. Cellenkos Inc, Houston, Texas, USA;4. Division of Hematology/Oncology, Department of Medicine, New York–Presbyterian Hospital, Columbia University Irving Medical Center, New York, New York, USA;5. Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael''s Hospital, Unity Health Toronto, University of Toronto, Toronto, Canada;1. Department of Hematology, Singapore General Hospital, Singapore, Republic of Singapore;2. Department of Clinical and Translational Research, Singapore General Hospital, Singapore, Republic of Singapore;3. Patient Services, Blood Services Group, Health Sciences Authority, Singapore, Republic of Singapore;4. Cell Therapy Facility, Blood Services Group, Health Sciences Authority, Singapore, Republic of Singapore;5. Infection and Immunity Clinical Academic Group, St George''s, University of London, London, UK |
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| Abstract: | Background aimsIn a previous pilot study of HLA-matched sibling donor hematopoietic cell transplantation (HCT), the authors determined the feasibility of day 4 versus day 5 granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) collection compared with a historical cohort. Given identified differences in the PBSC product (day 4 cohort with significantly lower infused total nucleated, mononuclear and CD3 cells compared with other collection cohorts), the authors performed a follow-up study to determine long-term post-HCT outcomes, including detailed characterization of chronic graft-versus-host disease (GVHD).MethodsThis was a prospective observational study, and the authors collected data on chronic GVHD, staging, sites of involvement and treatments. Performance status, incidence of relapse, overall survival and duration of immunosuppressive therapy (IST) were also evaluated. Data were examined retrospectively. To account for differences in length of follow-up among cohorts, the authors also determined performance status and chronic GVHD staging, sites and treatment at 2 years post-HCT.ResultsAt 2 years post-HCT, the overall survival rate was 71.7% in the day 4 cohort compared with 61.5%, 52% and 56% in the day 5, 2-day and historical cohorts, respectively (P = 0.283). The cumulative incidence of chronic GVHD was 65.2% in the day 4 cohort versus 46.4% in the day 5 cohort, 51.1% in the 2-day cohort and 65% in the historical cohort (P = 0.26). There was no significant difference in the maximum overall stage of chronic GVHD (P = 0.513), median number of sites involved (P = 0.401) or cumulative incidence of discontinuation of IST (P = 0.32). Death from chronic GVHD was less common in the day 4 and day 5 cohorts compared with the 2-day and historical cohorts, though this did not reach statistical significance.ConclusionsThe authors’ preliminary results demonstrated that collection of allogeneic matched sibling donor PBSCs on day 4 of G-CSF was feasible, reduced donor exposure to growth factor and was associated with an initial cost savings. Importantly, the authors now demonstrate that transplantation of day 4 mobilized PBSCs is not associated with any adverse outcomes post-HCT, including late effects such as chronic GVHD. Further investigation of donor G-CSF collection algorithms is merited in other HCT settings, including unrelated and mismatched related donors. |
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