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.
The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T-cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol.
Peggs
Karl S
KS
Department of Haematology, Royal Free and University College, London, UK. k.peggs@ucl.ac.uk
Sureda
Anna
A
Qian
Wendi
W
Caballero
Dolores
D
Hunter
Ann
A
Urbano-Ispizua
Alvaro
A
Cavet
James
J
Ribera
Josep M
JM
Parker
Anne
A
Canales
Miguel
M
Mahendra
Premini
P
Garcia-Conde
Javier
J
Milligan
Donald
D
Sanz
Guillermo
G
Thomson
Kirsty
K
Arranz
Reyes
R
Goldstone
Anthony H
AH
Alvarez
Ivan
I
Linch
David C
DC
Sierra
Jorge
J
Mackinnon
Stephen
S
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D008727:Methotrexate