Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report

• Published in: Bone marrow transplantation (Basingstoke) Vol. 36; no. 12; pp. 1097 - 1101
• Main Authors: SHAPIRA, M. Y, RESNICK, I. B, OR, R, BITAN, M, ACKERSTEIN, A, TSIRIGOTIS, P, GESUNDHEIT, B, ZILBERMAN, I, MIRON, S, LEUBOVIC, A, SLAVIN, S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.12.2005
• Subjects: Acute Disease; Adolescent; Adult; Alefacept; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Bacteremia; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Child; Complications and side effects; Dosage and administration; Drug Resistance; Drug therapy; Female; Fusion protein; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - pathology; Graft versus host disease; Graft versus host reaction; Graft vs Host Disease - drug therapy; Hemorrhage; Hemorrhagic cystitis; Humans; Immunomodulators; Infection; Liver; Liver - pathology; Lymphoma, Non-Hodgkin - therapy; Male; Medical sciences; Middle Aged; Myelodysplastic Syndromes - therapy; Pancytopenia; Patients; Pharmacology. Drug treatments; Pharynx; Physiological aspects; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Primary Myelofibrosis - therapy; Recombinant Fusion Proteins - therapeutic use; Risk factors; Side effects; Sinusitis; Skin; Skin - pathology; Skin Abnormalities - therapy; Stem cell transplantation; Steroids; Steroids (Drugs); Steroids - pharmacology; T-Lymphocytes - metabolism; Time Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Conditioning; Treatment Outcome; Israel; Human; Corticosteroid; Treatment resistance; Hematology; Acute; Homograft; Graft versus host reaction; Malignant hemopathy; Non Hodgkin lymphoma; Myelodysplastic syndrome; allogeneic bone marrow transplantation; Alefacept; Cancerology; Treatment; corticosteroids; Lymphoproliferative syndrome; Immunotherapy; Bone marrow; Graft; Complication; Immunosuppressive agent; Acute lymphocytic leukemia; graft-versus-host disease
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1705185

We evaluated the effect of alefacept (Amevive), a novel dimeric fusion protein, in steroid resistant/dependent acute graft-versus-host-disease (aGVHD). Seven patients were treated in eight aGVHD episodes. GVHD grade at treatment initiation and at peak ranged 2-4 (median 2.5) and 2-4 (median 4), respectively. System involvement at GVHD peak included skin (n=7), gastrointestinal tract (n=5) and liver (n=3). All patients responded. However, one patient with skin GVHD and two with gastrointestinal GVHD featuring an early initial response (IR) exacerbated and CR was not achieved. Skin GVHD responded rapidly with a median of 1 day to IR and 7 days to CR. Intestinal response was slower with median 7.5 days to IR. Of the four patients that achieved IR, CR was achieved in only one (40 days to CR). None of the patients had significant hepatic GVHD before treatment so no hepatic effect of alefacept could be determined. No immediate alefacept-related side effects were observed. Late side effects included infections (aspergillus sinusitis, pneumonia, bacteremia, pharyngeal thrush), pancytopenia and hemorrhagic cystitis. Three patients had CMV reactivation while on alefacept. We conclude that alefacept may have a beneficial effect in controlling aGVHD. Further investigations in larger cohorts of patients and controlled studies are warranted.