Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?
The anti-CD52 (Campath-1) monoclonal antibodies (Mabs) have a substantial history of use for controlling graft-versus-host disease in allogeneic bone marrow transplantation. Now, with the availability of a humanised form, alemtuzumab (Campath-1H), and the demonstration that this agent can reduce the tumour burden in B-CLL, a new niche may be found - as a potentially curative agent in which its tumour purging ability in vivo combines with its role as a conditioning agent in nonmyeloablative transplantation. Review of the literature shows that alemtuzumab has unique advantages as a method of depleting malignant lymphocytes, including those in patients resistant to conventional chemotherapy. Alemtuzumab can also be used in BMT for depletion of normal T and B lymphocytes of both the recipient and donor for prevention of graft rejection and GVHD. It allows good stem cell recovery with resultant rapid engraftment, has a low risk of EBV-triggered secondary malignancy and does not interfere with blood stem cell mobilisation. As a method of eliminating the malignant clone in B-CLL, alemtuzumab has shown remarkable efficacy in heavily pre-treated patients, a number of whom have progressed to autologous or allogeneic transplantation. Efficacy data are shown within the context of other transplantation data for B-CLL. These results indicate that the combination of tumour-depleting and immunosuppressive properties of alemtuzumab should be explored, with the hope of providing improved treatment options for elderly patients with advanced B-CLL or indolent lymphoma whose prognosis is too poor currently to allow treatment with traditional regimens of high-dose myeloablative chemotherapy.
Hale
G
G
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Slavin
S
S
Goldman
J M
JM
Mackinnon
S
S
Giralt
S
S
Waldmann
H
H
D000328:Adult; D000368:Aged; 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*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000628:therapy; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; 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; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine