Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84355
Title:
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.
Authors:
Pérez-Simón, José A; Kottaridis, Panagiotis D; Martino, Rodrigo; Craddock, Charles; Caballero, Dolores; Chopra, Rajesh; García-Conde, Javier; Milligan, Donald W; Schey, Stephen; Urbano-Ispizua, Alvaro; Parker, Anne; Leon, Angel; Yong, Kwee; Sureda, Anna; Hunter, Ann; Sierra, Jordi; Goldstone, Anthony H; Linch, David C; San Miguel, Jesus F; Mackinnon, Stephen
Abstract:
Although 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.
Affiliation:
Department of Hematology, Hospital Universitairo de Salamanca, Paseo de San Vicente s/n, 37007 Salamanca, Spain. pesimo@usal.es
Citation:
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. 2002, 100 (9):3121-7 Blood
Journal:
Blood
Issue Date:
1-Nov-2002
URI:
http://hdl.handle.net/10541/84355
DOI:
10.1182/blood-2002-03-0701
PubMed ID:
12384408
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPérez-Simón, José Aen
dc.contributor.authorKottaridis, Panagiotis Den
dc.contributor.authorMartino, Rodrigoen
dc.contributor.authorCraddock, Charlesen
dc.contributor.authorCaballero, Doloresen
dc.contributor.authorChopra, Rajeshen
dc.contributor.authorGarcía-Conde, Javieren
dc.contributor.authorMilligan, Donald Wen
dc.contributor.authorSchey, Stephenen
dc.contributor.authorUrbano-Ispizua, Alvaroen
dc.contributor.authorParker, Anneen
dc.contributor.authorLeon, Angelen
dc.contributor.authorYong, Kweeen
dc.contributor.authorSureda, Annaen
dc.contributor.authorHunter, Annen
dc.contributor.authorSierra, Jordien
dc.contributor.authorGoldstone, Anthony Hen
dc.contributor.authorLinch, David Cen
dc.contributor.authorSan Miguel, Jesus Fen
dc.contributor.authorMackinnon, Stephenen
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.en
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

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