Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.
AuthorsPérez-Simón, José A
Kottaridis, Panagiotis D
Milligan, Donald W
Goldstone, Anthony H
Linch, David C
San Miguel, Jesus F
AffiliationDepartment of Hematology, Hospital Universitairo de Salamanca, Paseo de San Vicente s/n, 37007 Salamanca, Spain. firstname.lastname@example.org
MetadataShow full item record
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.
CitationNonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. 2002, 100 (9):3121-7 Blood
- The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation.
- Authors: Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A, Clark FJ, Hunt L, Yin J, Fuller S, Vandenberghe E, Marsh J, Littlewood T, Smith GM, Culligan D, Hunter A, Chopra R, Davies A, Towlson K, Williams CD
- Issue date: 2002 Nov 1
- In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.
- Authors: Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S
- Issue date: 2000 Oct 1
- A study of a reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation for patients with hematologic malignancies using Campath-1H as part of a graft-versus-host disease strategy.
- Authors: Shore T, Harpel J, Schuster MW, Roboz GJ, Leonard JP, Coleman M, Feldman EJ, Silver RT
- Issue date: 2006 Aug
- Intensive graft-versus-host disease prophylaxis is required after unrelated-donor nonmyeloablative stem cell transplantation.
- Authors: Loren AW, Luger SM, Stadtmauer EA, Tsai DE, Schuster S, Nasta SD, Goldstein SC, Perl A, Orloff G, Oliver JC, Green J, Emerson SG, Porter DL
- Issue date: 2005 May
- Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes.
- Authors: Peggs KS, Sureda A, Qian W, Caballero D, Hunter A, Urbano-Ispizua A, Cavet J, Ribera JM, Parker A, Canales M, Mahendra P, Garcia-Conde J, Milligan D, Sanz G, Thomson K, Arranz R, Goldstone AH, Alvarez I, Linch DC, Sierra J, Mackinnon S, UK and Spanish Collaborative Groups.
- Issue date: 2007 Oct