title: Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen.
abstract: Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Hospital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, AP-HP, UPMC University of Paris 06, UMR-S 938, CEREST-TC EBMT, France Cord Blood Committee EBMT, University of Genova, Italy annalisa.ruggeri@sls.aphp.fr.
authors: Annalisa
authors: A
authors: Ruggeri
authors: Hospital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, AP-HP, UPMC University of Paris 06, UMR-S 938, CEREST-TC EBMT, France.
authors: Myriam
authors: M
authors: Labopin
authors: Biostatistics Unit, Department of Health Sciences (DISSAL), University of Genova, Italy.
authors: Maria Pia
authors: MP
authors: Sormani
authors: Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Guillermo
authors: G
authors: Sanz
authors: Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Jaime
authors: J
authors: Sanz
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France.
authors: Fernanda
authors: F
authors: Volt
authors: Hôpital d'Enfants de la Timone, Marseille, France.
authors: Gerard
authors: G
authors: Michel
authors: Dipartimento di Oncoematologia Pediatrica, Ospedale Bambino Gesù, IRCSS, Rome/University of Pavia, Italy.
authors: Franco
authors: F
authors: Locatelli
authors: Servicio de Hematologia y Oncologia Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
authors: Cristina
authors: C
authors: Diaz De Heredia
authors: Sydney Children's Hospital, Sydney, Australia.
authors: Tracey
authors: T
authors: O'Brien
authors: Rome Transplant Network, University Tor Vergata, Rome, Italy.
authors: William
authors: W
authors: Arcese
authors: Università La Sapienza, Dip. Biotecnologie Cellulari ed Ematologia, Rome, Italy.
authors: Anna Paola
authors: AP
authors: Iori
authors: Barcelona Cord Blood Bank, Barcelona, Spain.
authors: Sergi
authors: S
authors: Querol
authors: Dusseldorf Cord Blood Bank, University of Dusseldorf, Germany.
authors: Gesine
authors: G
authors: Kogler
authors: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Lucilla
authors: L
authors: Lecchi
authors: Besançon Cord Blood Bank of the Etablissement Français du Sang, Besançon, France.
authors: Fabienne
authors: F
authors: Pouthier
authors: Agence de la Biomedecine, Paris, France.
authors: Federico
authors: F
authors: Garnier
authors: NHS-Cord Blood Bank, NHSBT, Colindale Ave, and University College London, UK.
authors: Cristina
authors: C
authors: Navarrete
authors: Liege Cord Blood Bank, University of Liege, Belgium.
authors: Etienne
authors: E
authors: Baudoux
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France.
authors: Juliana
authors: J
authors: Fernandes
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France.
authors: Chantal
authors: C
authors: Kenzey
authors: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Mary
authors: M
authors: Eapen
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Monacord, Centre Scientifique de Monaco, Monaco.
authors: Eliane
authors: E
authors: Gluckman
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Churchill Hospital, Oxford University Hospitals, UK.
authors: Vanderson
authors: V
authors: Rocha
authors: Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Careggi University Hospital, Florence, Italy.
authors: Riccardo
authors: R
authors: Saccardi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists