Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Societe Francophone d'Histocompatibilite et d'Immunogenetique (SFHI) and Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) analysis

Ruggeri, Annalisa; Rocha, Vanderson; Masson, Emeline; Labopin, Myriam; Cunha, Renato; Absi, Léna; Boudifa, Ali; Coeffic, B.; Devys, Anne; Matteis, M de; Dubois, Valérie; Hanau, Daniel; Hau, F.; Jollet, Isabelle; Masson, Dominique; Pédron, Béatrice; Perrier, P.; Picard, Christophe; Ramouneau-Pigot, Annie; Volt, Fernanda; Charron, Dominique; Gluckman, Éliane; Loiseau, Pascale

doi:10.3324/haematol.2012.077685

Cited by 120 publications

(84 citation statements)

References 27 publications

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“…Different studies found an increased risk of graft failure in the presence of donor-specific anti-HLA antibodies in both single and double UCBT after myeloablative conditioning regimens 21 and reduced intensity conditioning. 22 However, due the retrospective character of our study, we were not able to analyze the impact of anti-HLA antibodies in this series of UCBT recipients.…”

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confidence: 99%

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Ruggeri¹,

Labopin²,

Sormani³

et al. 2014

Haematologica

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on behalf of Eurocord, Cord Blood Committee EBMT and NetcordInternational audienceUmbilical 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

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confidence: 99%

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Ruggeri¹,

Labopin²,

Sormani³

et al. 2014

Haematologica

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“…17 Other factors contributing to risk of graft rejection include the presence of donor-specific anti-HLA antibodies, which have been associated with both failed engraftment and higher TRM. 18 Recipient antibodies against mismatched donor HLA-DP have also been shown in 10/10 matched MUD alloSCT to be associated with a higher incidence of graft failure and mortality. 19 Risk of rejection also increases with increasing numbers of mismatches at HLA-A, -B, -C and -DR loci.…”

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confidence: 99%

Umbilical cord blood graft engineering: challenges and opportunities

Thompson

Rezvani

Hosing

et al. 2015

Bone Marrow Transplant

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We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specificT-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

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“…Moreover, although a haplo-identical donor was indicated as available in 85 patients, only two such transplants were planned. This reflects the usual transplant team practice for the period of this study, and it is likely that the feasibility of UD transplants has increased recently with new transplant modalities developed for CB 11,12 and haplo-mismatch transplants. 13,14 The primary objective of this study was to evaluate the allocation of patients to pre-defined therapies in EBMT centers and to assess feasibility and deviations from initial treatment assignments.…”

Section: Discussionmentioning

confidence: 99%

A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality

Labopin

Gorin

Polge

et al. 2013

Bone Marrow Transplant

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For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR ¼ 0.82; P ¼ 0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

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Cited by 120 publications

References 27 publications

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Umbilical cord blood graft engineering: challenges and opportunities

A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality

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