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.

TitleFrequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.
Publication TypeJournal Article
Year of Publication2016
AuthorsTsai SB, Liu H, Shore T, Fan Y, Bishop M, Cushing MM, Gergis U, Godley L, Kline J, Larson RA, Martinez G, Mayer S, Odenike O, Stock W, Wickrema A, Van Besien K, Artz AS
JournalBiol Blood Marrow Transplant
Volume22
Issue6
Pagination1065-1072
Date Published2016 06
ISSN1523-6536
KeywordsAdolescent, Adult, Aged, Antigens, CD34, Chimerism, Cord Blood Stem Cell Transplantation, Female, Fetal Blood, Graft Rejection, Haploidy, Histocompatibility, Humans, Male, Middle Aged, Risk Factors, Survival Analysis, Transplantation Conditioning, Transplantation, Haploidentical, Young Adult
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.

DOI10.1016/j.bbmt.2016.02.010
Alternate JournalBiol Blood Marrow Transplant
PubMed ID26912055
PubMed Central IDPMC4867292
Grant ListK12 CA139160 / CA / NCI NIH HHS / United States
K24 CA116471 / CA / NCI NIH HHS / United States
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