title: Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.
abstract: Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34(+) selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical-autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34(+) cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois; Section of Hematology-Oncology, Department of Medicine, Loyola University Medical Center, Maywood, Illinois. Electronic address: s13@bu.edu.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Tsai
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Hematopoietic Stem Cell Transplant Program, Weill-Cornell Medical College, New York, New York.
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.affiliation: Department of Hematology, Beijing Hospital, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Bishop
authors.affiliation: Department of Pathology, Weill-Cornell Medical College, New York, New York.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Cushing
authors.affiliation: Hematopoietic Stem Cell Transplant Program, Weill-Cornell Medical College, New York, New York.
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Lucy
authors.initials: L
authors.lastname: Godley
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: Stem Cell Laboratory, Department of Hematology, University of Chicago, Chicago, Illinois.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Martinez
authors.affiliation: Hematopoietic Stem Cell Transplant Program, Weill-Cornell Medical College, New York, New York.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: Section of Hematology-Oncology, Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
authors.forename: Olatoyosi
authors.initials: O
authors.lastname: Odenike
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.affiliation: Department of Pathology, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Amittha
authors.initials: A
authors.lastname: Wickrema
authors.affiliation: Hematopoietic Stem Cell Transplant Program, Weill-Cornell Medical College, New York, New York.
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Artz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D046528:Chimerism; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006238:Haploidy; D006648:Histocompatibility; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D000075442:Transplantation, Haploidentical / Q000379:methods; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: Allogeneic stem cell transplantation; Alternative donor; Graft failure; Haploidentical graft; umbilical cord blood