Early fluid overload is associated with an increased risk of nonrelapse mortality after ex vivo CD34-selected allogeneic hematopoietic cell transplantation Journal Article


Authors: Rondon-Clavo, C.; Scordo, M.; Hilden, P.; Shah, G. L.; Cho, C.; Maloy, M. A.; Papadopoulos, E. B.; Jakubowski, A. A.; O'Reilly, R. J.; Gyurkocza, B.; Castro-Malaspina, H.; Tamari, R.; Shaffer, B. C.; Perales, M. A.; Jaimes, E. A.; Giralt, S. A.
Article Title: Early fluid overload is associated with an increased risk of nonrelapse mortality after ex vivo CD34-selected allogeneic hematopoietic cell transplantation
Abstract: In a recently published and validated definition of fluid overload (FO), grade ≥ 2 FO was significantly associated with an increased risk of nonrelapse mortality (NRM) after unmodified and haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis. We evaluated the effect of FO on outcomes in 169 patients undergoing myeloablative-conditioned ex vivo CD34+ selected allo-HCT using the same grading scale. Thirty patients (17.8%) had grade ≥ 2 FO within the 30 days after ex vivo CD34+ selected allo-HCT with a median onset at day 11 (range, -8 to 28). Age ≥ 55 years (odds ratio, 3.43; P =.005) and chemotherapy-based conditioning (odds ratio, 3.89; P =.007) were associated with an increased risk of grade ≥ 2 FO. Patients with early grade ≥ 2 FO had a significantly higher NRM when compared with patients with grade < 2 FO (24.1% versus 3.6% at day 100, P =.01). The HCT-specific comorbidity index (HCT-CI) ≥ 3, FEV1 < 80, adjusted DLco < 80, and HLA mismatch were associated with an increased risk of NRM, whereas total body irradiation–based conditioning was associated with a reduced risk of NRM. In a multivariate analysis grade ≥ 2 FO was associated with increased NRM after adjusting for HCT-CI and HLA match (hazard ratio, 2.3; P =.014). There was a trend toward inferior relapse-free survival in patients with grade ≥ 2 FO compared with patients with grade < 2 FO, 62% versus 72% at 1 year (P =.07), and a trend toward inferior overall survival, 69% versus 79% at 1 year (P = 0.06), respectively. Our findings show that FO should be routinely assessed to identify patients at risk for NRM. Despite a CNI-free allo-HCT platform, regimen-related tissue and endothelial injury leads to FO in susceptible patients. FO is a highly relevant post-HCT toxicity that requires further inquiry. © 2018
Keywords: adult; major clinical study; overall survival; busulfan; fludarabine; mortality; outcome assessment; cd34 antigen; cyclophosphamide; melphalan; risk factor; thiotepa; electronic medical record; acute graft versus host disease; myeloablative conditioning; whole body radiation; prophylaxis; allogeneic hematopoietic stem cell transplantation; dna sequence; toxicity; hla typing; ex vivo study; granulocyte colony stimulating factor; keratinocyte growth factor; clofarabine; thymocyte antibody; recurrence free survival; endothelium injury; liver venoocclusive disease; conditioning; fluid overload; hypervolemia; human; male; female; article; nonrelapse mortality; comorbidity assessment; ex vivo cd34-selected allogeneic transplantation
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 24
Issue: 12
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2018-12-01
Start Page: 2517
End Page: 2522
Language: English
DOI: 10.1016/j.bbmt.2018.07.031
PROVIDER: scopus
PMCID: PMC6286243
PUBMED: 30055353
DOI/URL:
Notes: Biol. Blood Marrow Transplant. -- Export Date: 2 January 2019 -- Article -- CODEN: BBMTF C2 - 30055353 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Sergio Andres Giralt
    500 Giralt
  2. Miguel-Angel Perales
    355 Perales
  3. Richard O'Reilly
    462 O'Reilly
  4. Molly Anna Maloy
    118 Maloy
  5. Christina Cho
    34 Cho
  6. Roni Tamari
    72 Tamari
  7. Michael Scordo
    29 Scordo
  8. Patrick Dale Hilden
    79 Hilden
  9. Gunjan Lalitchandra Shah
    67 Shah
  10. Edgar Alberto Jaimes
    23 Jaimes
  11. Brian Carl Shaffer
    40 Shaffer