Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.

2.50
Hdl Handle:
http://hdl.handle.net/10541/87663
Title:
Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.
Authors:
Patel, Bella; Kirkland, Keiren E; Szydlo, Richard; Pearce, Rachel M; Clark, Richard E; Craddock, Charles; Liakopoulou, Effie F; Fielding, Adele K; Mackinnon, Stephen; Olavarria, Eduardo; Potter, Mike N; Russell, Nigel; Shaw, Bronwen E; Cook, Gordon; Goldstone, Anthony H; Marks, David I
Abstract:
BACKGROUND: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known. DESIGN AND METHODS: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005. RESULTS: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045). CONCLUSIONS: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.
Affiliation:
Department of Haematology, Royal Free and University College London Medical School, and BSBMT Data Registry, Guy's Hospital, London, UK.
Citation:
Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission. 2009, 94 (10):1399-406 Haematologica
Journal:
Haematologica
Issue Date:
Oct-2009
URI:
http://hdl.handle.net/10541/87663
DOI:
10.3324/haematol.2009.008649
PubMed ID:
19648167
Type:
Article
Language:
en
ISSN:
1592-8721
Appears in Collections:
All Christie Publications ; Haematology

Full metadata record

DC FieldValue Language
dc.contributor.authorPatel, Bellaen
dc.contributor.authorKirkland, Keiren Een
dc.contributor.authorSzydlo, Richarden
dc.contributor.authorPearce, Rachel Men
dc.contributor.authorClark, Richard Een
dc.contributor.authorCraddock, Charlesen
dc.contributor.authorLiakopoulou, Effie Fen
dc.contributor.authorFielding, Adele Ken
dc.contributor.authorMackinnon, Stephenen
dc.contributor.authorOlavarria, Eduardoen
dc.contributor.authorPotter, Mike Nen
dc.contributor.authorRussell, Nigelen
dc.contributor.authorShaw, Bronwen Een
dc.contributor.authorCook, Gordonen
dc.contributor.authorGoldstone, Anthony Hen
dc.contributor.authorMarks, David Ien
dc.date.accessioned2009-12-09T14:22:27Z-
dc.date.available2009-12-09T14:22:27Z-
dc.date.issued2009-10-
dc.identifier.citationFavorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission. 2009, 94 (10):1399-406 Haematologicaen
dc.identifier.issn1592-8721-
dc.identifier.pmid19648167-
dc.identifier.doi10.3324/haematol.2009.008649-
dc.identifier.urihttp://hdl.handle.net/10541/87663-
dc.description.abstractBACKGROUND: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known. DESIGN AND METHODS: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005. RESULTS: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045). CONCLUSIONS: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.en
dc.language.isoenen
dc.subjectAdulten
dc.subjectAcute Lymphoblastic Leukaemiaen
dc.subjectStem Cell Transplantationen
dc.subjectT-Cell Depletionen
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntibodies, Neoplasm-
dc.subject.meshPhiladelphia Chromosome-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshStem Cell Transplantation-
dc.subject.meshTransplantation Conditioning-
dc.titleFavorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, Royal Free and University College London Medical School, and BSBMT Data Registry, Guy's Hospital, London, UK.en
dc.identifier.journalHaematologicaen

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