In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.
A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.
Kottaridis
P D
PD
Departments of Hematology, University College London Hospital, London, England.
Milligan
D W
DW
Chopra
R
R
Chakraverty
R K
RK
Chakrabarti
S
S
Robinson
S
S
Peggs
K
K
Verfuerth
S
S
Pettengell
R
R
Marsh
J C
JC
Schey
S
S
Mahendra
P
P
Morgan
G J
GJ
Hale
G
G
Waldmann
H
H
de Elvira
M C
MC
Williams
C D
CD
Devereux
S
S
Linch
D C
DC
Goldstone
A H
AH
Mackinnon
S
S
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000627:therapeutic use; D018895:Microsatellite Repeats; D008875:Middle Aged; D009679:Nuclear Family; D016133:Polymerase Chain Reaction; D012008:Recurrence; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D000074323:Alemtuzumab; D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D008727:Methotrexate