The graft-versus-leukemia effect in leukemia cutis.

Abstract

The benefit of allogeneic hematopoietic stem-cell transplantation (AHSCT) in patients with acute myeloid leukemia (AML) is largely related to the immune mediated graft-versus-leukemia (GvL) effect of the allografts. The curative potential of the GvL effect has been demonstrated by the ability of inducing remission upon withdrawal of immunosuppressive therapy or donor lymphocyte infusion in patients whose AML relapsed after transplant (1). We report here a patient who developed cutaneous relapse of his AML 2 months after AHSCT from his human leukocyte antigen (HLA)-identical sibling. Withdrawal of immunosuppression induced skin graft-versus-host disease (GvHD) and an immediate, complete remission (CR) of his leukemia cutis. A 65-year-old male was diagnosed with stage IIIa diffuse large cell lymphoma in February 1997. He was treated with chemotherapy and achieved a CR until January 1999, when he developed progressive fatigue. Bone-marrow study showed AML (French-American-British [FAB] classification: AML M5) with multiple cytogenetic abnormalities. He achieved a CR after induction chemotherapy with cyclophosphamide, cytarabine, and topotecan followed by consolidation chemotherapy. In June 2001, he developed relapse of his leukemia in skin and bone marrow, which was confirmed on histology. He received clofarabine as salvage therapy and achieved a new CR in both his skin and bone marrow. In January 2002, he received a peripheral blood stem-cell transplantation from an HLA-matched sibling using fludarabine and busulfan as conditioning regimen. Tacrolimus and methotrexate were used for prophylaxis of GvHD. Day 30 work-up showed that he was in CR with complete donor chimerism. On day 36, he developed grade II skin GvHD as confirmed by skin biopsy. His skin GvHD progressed to stage III, which responded to systemic steroids. On day 65 posttransplant, he developed a new widespread, round, raised, erythematous, papular rash on his trunk and limbs. Skin biopsy showed leukemia cutis (Fig. 1a). Repeat bone-marrow study showed no evidence of leukemia, and there was complete donor chimerism. Tacrolimus was withdrawn on day 71, and steroids were rapidly tapered off. His papular rash gradually resolved, but he developed a new maculopapular rash over the resolving leukemia cutis. A repeat skin biopsy performed on day 100 showed GvHD but no leukemic infiltrates (Fig. 1b). His grade II skin GvHD responded to topical steroids. On his 9-month follow-up, he remained in CR and off immunosuppression. Figure 1: (a) Skin biopsy obtained on day 65 posttransplant. Note the dense, mononuclear infiltrate in the dermis compatible with leukemia cutis. (b) Skin biopsy obtained on day 100 posttransplant. There was interface dermatitis with mild lymphocytic infiltrate and vacuolization of basal keratinocytes. There was no evidence of leukemia cutis.Leukemia cutis is considered a poor prognostic sign in patients with acute leukemia (2,3). Analysis of reported case series indicate that systemic chemotherapy can induce sustained bone-marrow remissions but rarely controls leukemia cutis (4). Local therapy using electron-beam irradiation is a treatment option, but it does not prevent bone-marrow relapse (4). Systemic chemotherapy combined with electron-beam irradiation has been reported to induce long-term disease-free survival (4,5). Skin is a common site of GvHD, an immune-mediated effect of the allograft. In our patient, the temporal relationship of development of skin GvHD and resolution of leukemia cutis after withdrawal of immunosuppression is a convincing evidence of GvL effect. Our case demonstrated that the GvL effect following AHSCT can be effective against leukemia cutis. Raymond Wong Daniel Couriel Victor G. Prieto