title: Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report.
abstract: 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.
authors.affiliation: Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah - Hebrew University Medical Center, Jerusalem, Israel. shapiram@hadassah.org.il
authors.forename: M Y
authors.initials: MY
authors.lastname: Shapira
authors.forename: I B
authors.initials: IB
authors.lastname: Resnick
authors.forename: M
authors.initials: M
authors.lastname: Bitan
authors.forename: A
authors.initials: A
authors.lastname: Ackerstein
authors.forename: P
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: B
authors.initials: B
authors.lastname: Gesundheit
authors.forename: I
authors.initials: I
authors.lastname: Zilberman
authors.forename: S
authors.initials: S
authors.lastname: Miron
authors.forename: A
authors.initials: A
authors.lastname: Leubovic
authors.forename: S
authors.initials: S
authors.lastname: Slavin
authors.forename: R
authors.initials: R
authors.lastname: Or
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000077944:Alefacept; D016026:Bone Marrow Transplantation; D002648:Child; D004351:Drug Resistance; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007239:Infections; D008099:Liver / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D055728:Primary Myelofibrosis / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology; D012868:Skin Abnormalities / Q000628:therapy; D013256:Steroids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D011993:Recombinant Fusion Proteins; D013256:Steroids; D000077944:Alefacept