Prevention of graft vs. host disease with alemtuzumab 'in the bag' decreases early toxicity of stem cell transplantation and in multiple myeloma is associated with improved long-term outcome.
BACKGROUND
Allogeneic stem cell transplantation in multiple myeloma (MM) is controversial because treatment-related mortality and relapse remain a substantial challenge.


METHODS
Patients with symptomatic MM responsive to therapy received myeloablative conditioning with radiotherapy (n=12) or chemotherapy (n=10) followed by infusion of HLA-identical grafts from a sibling. Graft vs. host disease (GvHD) prophylaxis consisted of 'ex vivo' T-cell depletion with CAMPATH-1 antibody. The objective of the study was to determine transplant-related mortality (TRM), GvHD, overall survival (OS) and Disease free Survival (DFS).


RESULTS
Twenty-two patients, median age 45 (range 37-56) years, had a median performance status of 1 (0-2). Patients received a median of 23.8 x 10(4)/kg CFU-GM and 4.31 x 10(6)/kg CD34. Median time to engraftment was 13 days. The day-100 and 1-year TRM was 9% and 20%, respectively. Ten patients suffered disease recurrence. Four of eight patients remained in remission after infusions of donor lymphocyte (DLI) containing a median total of 0.67 x 10(8)/kg CD3 cells. Three-year OS was 56%, and 50% remained disease free at a median of 1101 days (range 385-5309). Multiple regression analysis showed that bone marrow (vs. peripheral blood stem cell) (P=0.03), presentation of low albumin (P=0.02) and a higher dose of CAMPATH-1H (P=0.01) were adverse factors for survival. Cox analysis confirmed that a lower CAMPATH-1H dose was associated with improved outcome.


CONCLUSIONS
In chemotherapy-responsive patients with myeloma, T-cell depletion of allogeneic grafts was associated with an acceptable 1-year TRM and seemed to have a favorable impact on long-term survival.
Novitzky
N
N
Groote Schuur Hospital, Observatory, University of Cape Town Leukaemia Centre and Department of Haematology, Cape Town, South Africa. Nicolas.Novitzky@uct.ac.za
Thomas
V
V
du Toit
C
C
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000074301:CD52 Antigen; D018572:Disease-Free Survival; D006023:Glycoproteins / Q000276:immunology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab