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Treatment of Severe Systemic Sclerosis with Allogeneic Marrow Transplantation

Treatment of Severe Systemic Sclerosis with Allogeneic Marrow Transplantation

Blood 100(11): Abstract No 5418, November 16

Allogeneic marrow transplantation (MT) was evaluated in 2 patients (pts) for control of severe systemic sclerosis (SSc). Both pts received a myeloablative conditioning regimen consisting of busulfan (Css=700 ng/ml), cyclophosphamide (120 mg/kg) and ATG (90 mg/kg) and MT from HLA-matched siblings. Case 1: The patient (pt) was a 38 y.o. female who was diagnosed with SSc in Feb. 1997. The pt was profoundly disabled with severe pulmonary dysfunction (DLCO=43%, FVC= 68%) and diffuse scleroderma with a Rodnan skin score of 36 at baseline. Renal and cardiac function were normal. The pt was anti-nuclear antibody (ANA) positive but Scl-70 negative. Treatment with conventional agents including penicillamine and cyclophosphamide failed. Patient was transplanted with marrow in Mar. 1999 and received cyclosporine (CSP) and methotrexate (MTX) for GVHD prophylaxis. Posttransplant course was complicated with a bacterial pneumonia on day 51 which resolved. No GVHD treatment was required and CSP was discontinued 7 months after transplantation. There were no significant cardiac or renal complications. At 3 years after transplantation, DLCO was unchanged at 40% and FVC was markedly improved to 95%. There was no worsening of the bilateral interstitial infiltrates identified at baseline on high-resolution CT scans of the chest. Rodnan skin score was decreased to 2. Patient's overall function had improved with a decrease in the score of the Health Assessment Questionnaire (mHAQ) from 1.35 to 0.25. There was no recurrence of digital ulcerations after MT. In both the CD3+ and CD33+ compartments, there was 100% donor chimerism. Case 2: Patient was a 31 y.o. female who was diagnosed in Oct. 1998. The pt had pulmonary dysfunction ( DLCO= 63%, FVC= 64%) and a Rodnan skin score of 40. Renal and cardiac function were normal. The pt was ANA positive and Scl-70 negative. Treatment with penicillamine and methotrexate failed. The pt was transplanted with marrow in Aug. 2000. GVHD prophylaxis was CSP and MTX. The pt developed acute GVHD and was treated with prednisone on day 37. The pt developed a hypertensive crisis on day 39 with seizures and renal failure not requiring dialysis. Dose of prednisone was decreased and mycophenolate mofetil (MMF) started. T cells were 99% donor at 100 days. Chronic GVHD developed after day 100 (after prednisone and MMF were discontinued), and the patient was started on a prolonged course with those agents. Late posttransplant course was complicated by flares of chronic GVHD, pulmonary aspergillosis and nocardia. These late complications resolved on treatment and the pt was tapering immunosuppressive therapy. At 16 months the Rodnan skin score had decreased to 11 and the mHAQ had decreased from 2.125 to 0.75. At 18 months, before returning to Seattle for subsequent pulmonary function tests (PFT), the pt presented to hospital with overwhelming pseudomonas sepsis and died. Conclusions: Although the experience is still limited, these 2 cases demonstrate that scleroderma significantly improves after allogeneic MT. Although only one pt had PFT at more than 1 year, DLCO did not improve even though there was marked improvement in FVC. Management of acute GVHD with high-dose prednisone may be complicated with hypertensive crisis. The risks of allogeneic MT must be carefully weighed before pts are considered for treatment and all pts should be enrolled in clinical trials.

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Accession: 035980612

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