Effects of Late Toxicities on Outcomes in Long-Term Survivors of Ex-Vivo CD34+-Selected Allogeneic Hematopoietic Cell Transplantation

• Published in: Biology of blood and marrow transplantation Vol. 24; no. 1; pp. 133 - 141
• Main Authors: Scordo, Michael, Shah, Gunjan L., Kosuri, Satyajit, Herrera, Diego Adrianzen, Cho, Christina, Devlin, Sean M., Maloy, Molly A., Nieves, Jimmy, Borrill, Taylor, Avecilla, Scott T., Meagher, Richard C., Carlow, Dean C., O'Reilly, Richard J., Papadopoulos, Esperanza B., Jakubowski, Ann A., Koehne, Guenther, Gyurkocza, Boglarka, Castro-Malaspina, Hugo, Tamari, Roni, Perales, Miguel-Angel, Giralt, Sergio A., Shaffer, Brian C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018
• Subjects: Adult; Aged; Allogeneic hematopoietic cell transplantation; Ex-vivo CD34+ cell selection; Female; Graft vs Host Disease - mortality; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Late toxicities; Long Term Adverse Effects; Male; Middle Aged; Myeloablative Agonists - adverse effects; Risk Factors; Survival Analysis; Survivors; Transplantation Conditioning - adverse effects; Transplantation, Homologous - adverse effects; Transplantation, Homologous - methods; Ex-vivo CD34+ cell selection; Allogeneic hematopoietic cell transplantation; Late toxicities; Ex-vivo CD34(+) cell selection
• ISSN: 1083-8791; 1523-6536; 1523-6536
• DOI: 10.1016/j.bbmt.2017.08.033

•We evaluated all high-grade toxicities in 1-year survivors of CD34+- selected allo-HCT.•HCT-CI ≥3 and GVHD in the first year resulted in more late toxicities, late NRM, and poorer OS.•Limiting toxicities in the first year and identifying those at risk for late toxicity may improve outcomes. 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.