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dc.contributor.authorPérez-Simón, José A
dc.contributor.authorKottaridis, Panagiotis D
dc.contributor.authorMartino, Rodrigo
dc.contributor.authorCraddock, Charles
dc.contributor.authorCaballero, Dolores
dc.contributor.authorChopra, Rajesh
dc.contributor.authorGarcía-Conde, Javier
dc.contributor.authorMilligan, Donald W
dc.contributor.authorSchey, Stephen
dc.contributor.authorUrbano-Ispizua, Alvaro
dc.contributor.authorParker, Anne
dc.contributor.authorLeon, Angel
dc.contributor.authorYong, Kwee
dc.contributor.authorSureda, Anna
dc.contributor.authorHunter, Ann
dc.contributor.authorSierra, Jordi
dc.contributor.authorGoldstone, Anthony H
dc.contributor.authorLinch, David C
dc.contributor.authorSan Miguel, Jesus F
dc.contributor.authorMackinnon, Stephen
dc.date.accessioned2009-10-16T14:48:59Z
dc.date.available2009-10-16T14:48:59Z
dc.date.issued2002-11-01
dc.identifier.citationNonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. 2002, 100 (9):3121-7 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid12384408
dc.identifier.doi10.1182/blood-2002-03-0701
dc.identifier.urihttp://hdl.handle.net/10541/84355
dc.description.abstractAlthough nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.
dc.language.isoenen
dc.subjectGraft vs Tumour Effecten
dc.subjectCancer Antibodiesen
dc.subjectHaematologic Canceren
dc.subject.meshAdult
dc.subject.meshAntibodies, Monoclonal
dc.subject.meshAntibodies, Neoplasm
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshCyclosporine
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshGraft vs Host Disease
dc.subject.meshGraft vs Tumor Effect
dc.subject.meshGreat Britain
dc.subject.meshHematologic Neoplasms
dc.subject.meshHumans
dc.subject.meshImmunosuppressive Agents
dc.subject.meshIncidence
dc.subject.meshInfection
dc.subject.meshLife Tables
dc.subject.meshLymphoproliferative Disorders
dc.subject.meshMale
dc.subject.meshMelphalan
dc.subject.meshMethotrexate
dc.subject.meshMiddle Aged
dc.subject.meshPeripheral Blood Stem Cell Transplantation
dc.subject.meshProspective Studies
dc.subject.meshSpain
dc.subject.meshTransplantation Conditioning
dc.subject.meshTransplantation, Homologous
dc.subject.meshTreatment Outcome
dc.subject.meshVidarabine
dc.titleNonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.en
dc.typeArticleen
dc.contributor.departmentDepartment of Hematology, Hospital Universitairo de Salamanca, Paseo de San Vicente s/n, 37007 Salamanca, Spain. pesimo@usal.esen
dc.identifier.journalBlooden
html.description.abstractAlthough nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.


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