Effects of late toxicities on outcomes in long-term survivors of ex-vivo CD34(+)-selected allogeneic hematopoietic cell transplantation Journal Article
| Authors: | Scordo, M.; Shah, G. L.; Kosuri, S.; Herrera, D. A.; Cho, C.; Devlin, S. M.; Maloy, M. A.; Nieves, J.; Borrill, T.; Avecilla, S. T.; Meagher, R. C.; Carlow, D. C.; O'Reilly, R. J.; Papadopoulos, E. B.; Jakubowski, A. A.; Koehne, G.; Gyurkocza, B.; Castro-Malaspina, H.; Tamari, R.; Perales, M. A.; Giralt, S. A.; Shaffer, B. C. |
| Article Title: | Effects of late toxicities on outcomes in long-term survivors of ex-vivo CD34(+)-selected allogeneic hematopoietic cell transplantation |
| Abstract: | The late adverse events in long-term survivors after myeloablative-conditioned allogeneic hematopoietic cell transplantation (HCT) with ex vivo CD34+ cell selection are not well characterized. Using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0, we assessed all grade ≥3 toxicities from the start of conditioning to the date of death, relapse, or last contact in 131 patients who survived >1 year post-HCT, identifying 285 individual toxicities among 17 organ-based toxicity groups. Pretransplantation absolute lymphocyte count >.5 K/µL and serum albumin >4.0 g/dL were associated with a reduced risk of toxicities, death, and nonrelapse mortality (NRM), whereas serum ferritin >1000 ng/mL was associated with an increased risk of toxicities and NRM after 1 year. An HCT Comorbidity Index (HCT-CI) score ≥3 was associated with an increased risk of all-cause death and NRM, but was not associated with a specific increased toxicity risk after 1 year. Patients who incurred more than the median number of toxicities (n = 7) among all patients within the first year subsequently had an increased risk of hematologic, infectious, and metabolic toxicities, as well as an increased risk of NRM and inferior 4-year overall survival (OS) (67% versus 86%; P =.003) after the 1-year landmark. The development of grade II-IV acute graft-versus-host disease (GVHD) within the first year was associated with incurring >7 toxicities within the first year (P =.016), and also with an increased risk of all-cause death and NRM after 1 year. In multivariate models, cardiovascular, hematologic, hepatic, infectious, metabolic, neurologic, and pulmonary toxicities incurred after 1 year were independently associated with increased risk of death and NRM when adjusting for both HCT-CI and grade II-IV acute GVHD within the first year. One-year survivors of ex vivo CD34+ selection had a favorable 4-year OS of 77%, although the development of grade ≥3 toxicities after the first year was associated with poorer outcomes, emphasizing the fundamental importance of improving survivorship efforts that may improve long-term toxicity burden and outcome. © 2017 The American Society for Blood and Marrow Transplantation |
| Keywords: | adult; aged; major clinical study; overall survival; busulfan; fludarabine; mortality; hypertension; outcome assessment; infection; multiple myeloma; lung disease; relapse; cyclophosphamide; melphalan; chronic myeloid leukemia; thiotepa; acute lymphoblastic leukemia; survivor; risk; alkaline phosphatase; cause of death; acute graft versus host disease; acute leukemia; chronic graft versus host disease; myelodysplastic syndrome; nonhodgkin lymphoma; death; cardiovascular disease; urinary tract infection; scoring system; sepsis; allogeneic hematopoietic stem cell transplantation; liver disease; cognitive defect; lymphoproliferative disease; hyperbilirubinemia; bacteremia; toxicity; lung infection; ex vivo study; neurologic disease; metabolic disorder; cd34 selection; cytopenia; clofarabine; national health organization; lymphocyte count; myeloproliferative neoplasm; hematologic disease; ferritin; upper respiratory tract infection; adult respiratory distress syndrome; ferritin blood level; allogeneic hematopoietic cell transplantation; prolymphocytic leukemia; serum albumin; hypertransaminasemia; acute myeloid leukemia; human; male; female; article; late toxicities; ex-vivo cd34+ cell selection |
| Journal Title: | Biology of Blood and Marrow Transplantation |
| Volume: | 24 |
| Issue: | 1 |
| ISSN: | 1083-8791 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2018-01-01 |
| Start Page: | 133 |
| End Page: | 141 |
| Language: | English |
| DOI: | 10.1016/j.bbmt.2017.08.033 |
| PROVIDER: | scopus |
| PUBMED: | 28870777 |
| PMCID: | PMC6713288 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 February 2018 -- Source: Scopus |
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