Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease.
The treatment of steroid-refractory acute graft-versus-host disease (aGVHD) remains a clinical challenge, for which no standard therapy exists. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) that has been successfully used as part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) to prevent GVHD. The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (>or=grade II) following HSCT. Eighteen patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days. Response was assessed at day 28 following initiation of alemtuzumab. Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV. The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3. Fifteen patients (83%) responded to alemtuzumab, including 6 (33%) with complete response. All 3 unresponsive patients died of GVHD. Ten of 15 responders are alive at median follow-up of 11 months (range: 3-24). Infections occurred in 14 patients, including cytomegalovirus (CMV) reactivation in 11. Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively. Alemtuzumab was well tolerated, and induces promising response rates in steroid-refractory aGVHD.
Gómez-Almaguer
David
D
Servicio de Hematología, Hospital Universitario Dr. José E. González, Universidad Autónoma Nuevo León, Monterrey, NL, México. dr_gomez@infosel.net.mx
Ruiz-Argüelles
Guillermo J
GJ
del Carmen Tarín-Arzaga
Luz
L
González-Llano
Oscar
O
Gutiérrez-Aguirre
Homero
H
Cantú-Rodríguez
Olga
O
Jaime-Pérez
José
J
Carrasco-Yalán
Antonio
A
Giralt
Sergio
S
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000074301:CD52 Antigen; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000009:adverse effects; D017211:Treatment Failure
D000305:Adrenal Cortex Hormones; 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