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
DOI/URL:
Notes: Article -- Export Date: 6 February 2018 -- Source: Scopus
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MSK Authors
  1. Sergio Andres Giralt
    537 Giralt
  2. Miguel-Angel Perales
    382 Perales
  3. Guenther Koehne
    175 Koehne
  4. Jimmy L . Nieves
    12 Nieves
  5. Richard O'Reilly
    487 O'Reilly
  6. Molly Anna Maloy
    133 Maloy
  7. Sean McCarthy Devlin
    305 Devlin
  8. Christina Cho
    38 Cho
  9. Roni Tamari
    78 Tamari
  10. Michael Scordo
    39 Scordo
  11. Richard Charles Meagher
    38 Meagher
  12. Gunjan Lalitchandra Shah
    81 Shah
  13. Satyajit   Kosuri
    23 Kosuri
  14. Dean Christian Carlow
    21 Carlow
  15. Brian Carl Shaffer
    45 Shaffer
  16. Taylor Wray Borrill
    12 Borrill