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Journal of Clinical Oncology, Vol 26, No 27 (September 20), 2008: pp. 4511-4513 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.6560
Complete Remission of Psoriasis After Autologous Hematopoietic Stem-Cell Transplantation for Multiple MyelomaDivision of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center; Graduate School of Biomedical Sciences at the University of Texas in Houston, TX
Department of Dermatology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX A 35-year-old white man with a 15-year history of psoriasis vulgaris and psoriatic arthropathy presented with vomiting, abdominal pain, anemia, acute renal failure, severe hypercalcemia, and numerous bony lytic lesions. Further testing confirmed the diagnosis of multiple myeloma with immunoglobulin A kappa restriction. A transient remission of the disease was achieved with bortezomib and dexamethasone treatment. The disease relapsed 4 months later, and the patient had a partial response after a modified regimen of cyclophosphamide, vincristine, doxorubicin, and dexamethasone. The treatment team decided to proceed with autologous peripheral hematopoietic stem-cell transplantation (HSCT). The psoriasis care in the pretransplant period was limited to phototherapy, topical agents such as calcipotriene, and topical corticosteroids (clobetasol, desonide, and triamcinolone). Despite the autoimmune nature of psoriasis,1 the patient was not a candidate for systemic immunosuppressive therapy because of the cytotoxicity of the agents used to treat the multiple myeloma. Immediately before his stem-cell transplant, the numerous symmetrically distributed erythematous plaques with silvery scales of psoriasis vulgaris covered 50% of the body-surface area, involving mainly the scalp, forehead, ears, back (Figs 1A and FIG 1C), upper chest (Fig 1B), and abdomen (Fig 1D). Additional guttate plaques with scale affected the extensor surface of the elbows and knees, and the nails exhibited distal onycholysis. The patient had a long 15-year history of arthralgias and oligoarticular spondyloarthritis. The patient received a 2-day standard myeloablative conditioning with intravenous melphalan (100 mg/m2 on day –3 and day –2 before HSCT followed by autologous peripheral HSCT (on day 0). Of note, the corticosteroids and phototherapy for the psoriasis have been discontinued before the time of HSCT because of risks of cumulative toxicity. Also, since the patient had an autologous HSCT, he did not receive any of the immunosuppressive agents usually used in cases of allogeneic transplants. The patient experienced a 1-year complete remission of myeloma, accompanied by complete regression of his psoriatic arthropathies and skin lesions though he was completely off corticosteroids and phototherapy. The patient also noted a complete resolution of the arthralgias from which he had suffered for more than a decade, despite remaining untreated for them. He remains psoriasis- and arthralgia-free 15 months later (Fig 2), although his myeloma has relapsed.
Psoriasis is an autoimmune disease which affects the skin and joints.1 The pathogenesis and therapeutic approaches to autoimmune disease remain a major clinical challenge. More than half a century ago, HSCT introduced a new arsenal of therapies into clinical practice, along with an array of complications. Indeed, autoimmune disease such as thyroiditis,2 ulcerative colitis,3,4 psoriasis,5 and scleroderma6 occur occasionally after autologous HSCT. The development of autoimmune diseases after allogeneic HSCT and cord blood transplantation7 has been documented as well,5,8 such as thyroiditis, insulin-dependent diabetes mellitus, myasthenia gravis, and vitiligo. In the case of allogeneic transplants, the causal relationship between the HSCT and the autoimmune disease remains speculative, but the possibility of passive transfer of autoimmune disease from donor to recipient has raised interest in the role of T cells in regulating such diseases.9 In large part because of these findings, for the last decade, researchers have studied HSCT specifically for the treatment of autoimmune disease.10 Indeed, allogeneic HSCT, both with myeloablative and nonmyeloablative regimens,11,12 has demonstrated encouraging therapeutic results in treating psoriasis,13-15 rheumatoid arthritis,16 systemic lupus erythematosus,11 and scleroderma.17 Whether a graft-versus-autoimmunity effect is a plausible therapeutic approach applicable to patient care remains conditional on the availability of less toxic nonmyeloablative regimens.18 Despite the negative reports of some development of a secondary autoimmune disease after autologous HSCT,19 most studies of transplants in patients already having autoimmune diseases have shown beneficial effects. When patients with concomitant long-standing autoimmune disease, were treated with autologous HSCT for hematological conditions (eg, aplasia or lymphomas), dramatic remissions were seen in the autoimmune disease.20 The results from well-conducted, but limited, studies of autologous HSCT's therapeutic effects on concomitant autoimmune disease in patients with hematological disorders have been mixed.21,22 In fact, responses of the autoimmune disease to autologous HSCT, with either myeloablative23 or nonmyeloablative24-26 conditioning regimens, provided prolonged remissions. This was achieved in multiple sclerosis,20,27-29 scleroderma,26,30,31 autoimmune thrombocytopenic purpura,32 systemic lupus erythematosus,21,33 scleromyxedema,34 Wegner's granulomatosis,35,36 and vasculitis.35 Recent reports document that this benefit is not transient but is long lived as autologous HSCT provide sustained improvement of skin condition and organ function in scleroderma24,30,37-39Why HSCT might have therapeutic value in autoimmune disease is still unclear.40 In the case of autologous HSCT, since patients receive their own hematopoietic stem cells, the remission of autoimmune disease thereafter has been attributed to a resetting of the immunological memory. This immune modulation may be secondary to myeloablative conditioning, where high-dose chemotherapy eliminates self-reactive lymphocytes, resulting in ablation of the peripheral autoreactive and alloreactive T cells and depletion of thymus cells and reactive B cells. The subsequent decrease in the level of autoantibodies thus contributes to immune tolerance.40 The reinfusion of autologous stem cells allows the establishment of lymphocytes de novo, which resets the arrangement of the different T-cell clones originally responsible for misrecognizing the auto-antigens as foreign antigens. Reconstitution of regulatory T cells and reactive B cells from naïve progenitors exposed to autoantigens may be responsible of regenerating self-tolerance.24,41,42 Additionally, autologous HSCT could increase cytokine production43 and possibly play a role in regenerating tissues damaged by the inflammatory process.41 AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS We thank Ms. Maude Veech for providing editorial review of the manuscript. REFERENCES 1. de Rie MA, Goedkoop AY, Bos JD: Overview of psoriasis. Dermatol Ther 17:341-349, 2004[CrossRef][Medline] 2. Bohgaki T, Atsumi T, Koike T: Multiple autoimmune diseases after autologous stem-cell transplantation. N Engl J Med 357:2734-2736, 2007 3. Koike K, Kohda K, Kuga T, et al: Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Bone Marrow Transplant 28:619-621, 2001[CrossRef][Medline] 4. Steinbach WJ, Sandborg CI: Development of systemic lupus erythematosus following autologous bone marrow transplant for acute lymphocytic leukemia. J Rheumatol 28:1467-1468, 2001 5. Wahie S, Alexandroff A, Reynolds NJ, et al: Psoriasis occurring after myeloablative therapy and autologous stem cell transplantation. Br J Dermatol 154:194-195, 2006[CrossRef][Medline] 6. 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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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