title: Hydroxychloroquine for the treatment of chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The manifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial responses were seen in 32 evaluable patients (53% response rate). All responders tolerated a >50% reduction in their steroid dose while receiving HCQ. Clinical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach for the treatment of extensive chronic GVHD.
authors.affiliation: Department of Pediatrics, The Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Gilman
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Mogul
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.forename: F D
authors.initials: FD
authors.lastname: Goldman
authors.forename: M
authors.initials: M
authors.lastname: Boyer
authors.forename: E
authors.initials: E
authors.lastname: Cirenza
authors.forename: A
authors.initials: A
authors.lastname: Mazumder
authors.forename: E
authors.initials: E
authors.lastname: Gehan
authors.forename: R
authors.initials: R
authors.lastname: Cahill
authors.forename: S
authors.initials: S
authors.lastname: Frankel
authors.forename: K
authors.initials: K
authors.lastname: Schultz
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D006886:Hydroxychloroquine