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.

Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft‐versus‐host disease

“…Less commonly, retinal toxicity, itching, intravascular hemolysis, skin rash, or bone marrow suppression can be seen. Toxicity to muscle and peripheral nerve has been rarely reported, and the incidence has been suggested to be low [1,11,12]. We report a severe case of hydroxychloroquine-induced myopathy with striking muscle pathology.…”

“…Hydroxychloroquine (Plaquenil), an anti-malarial drug, has been used increasingly in treating immunemediated diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and chronic graftversus-host disease (cGVHD) in bone marrow transplant patients [1]. The immune effects of this drug are multiple.…”

“…Hydroxychloroquine inhibits cytotoxicity caused by T cells, induces apoptosis in T cells, and in high concentrations, blocks T-cell activation [2][3][4]. It inhibits antigen processing and presentation through the major histocompatibility complex class II pathway and modulates cytokine production of, for example, IL-1, IL-6, and TNF [1,[5][6][7][8]. Hydroxychloroquine is an amphiphilic drug structurally similar to chloroquine but with a hydroxylated side chain as its name implies.…”

“…Hydroxychloroquine is an amphiphilic drug structurally similar to chloroquine but with a hydroxylated side chain as its name implies. Both chloroquine and hydroxychloroquine have been used in experimental and clinical models of GVHD [1,8]. It is synergistic with other drugs such as cyclosporine, tacrolimus, and sirolimus [9,10].…”

“…It is synergistic with other drugs such as cyclosporine, tacrolimus, and sirolimus [9,10]. The most common side effects of hydroxychloroquine are gastrointestinal disturbances [1]. Less commonly, retinal toxicity, itching, intravascular hemolysis, skin rash, or bone marrow suppression can be seen.…”