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• W2536103419 abstract "Abstract Abstract 3412 Poster Board III-300 Introduction High-dose cyclophosphamide (HD CY) is a potent immunosuppressive agent that is used as conditioning for HSCT in most patients with both hematologic malignancies and autoimmune diseases. HD CY is highly toxic to lymphocytes, but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase (the primary mechanism of CY inactivation). We and others have shown that HD CY without stem cell support can induce durable remissions in a variety of severe autoimmune diseases. Here, we report the long term follow-up of 124 patients with a variety of severe autoimmune diseases treated with HD CY. Methods From August 1996 through August 2008, 124 consecutive patients with severe, refractory autoimmune diseases (excluding acquired severe aplastic anemia) were treated with HD CY (50mg/kg/d) for 4 consecutive days without HSCT. Six days after the last dose of CY, all patients received granulocyte colony stimulating factor (5 μg/kg/day) until the neutrophil count exceeded 0.5 × 109/liter. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose or administration of a new immunosuppressive medication. Results The most common diseases treated with HD CY included lupus (n=42), multiple sclerosis (MS, n=32), myasthenia gravis (n=14) scleroderma (SSC, n=10), autoimmune hemolytic anemia (n=9) and pemphigus (n=9). The median follow up is 47 (range 1-127) months. All patients experienced rapid hematopoietic recovery: an absolute neutrophil count (ANC) > 500/μL was achieved at a median of 13 (range 8-22) days after the last dose CY and the median duration of an ANC < 500/μL was 9 (range 4-23) days. The median time to last platelet transfusion after completion of CY was 13 (range 0-33) days and the median time to last packed red blood cell transfusion was 12 (range 0-24) days. The median number of PRBC transfusions was 2 (range 0-27) and the median number of platelet transfusions was 2 (range 0-18.) The overall treatment related mortality was 0.8% with the lone death occurring in a non-neutropenic SSC patient on day 51 after HD CY. Median number of hospitalized days was 4 (range 0-55) days. The overall response rate was 94% with 42% of responders maintaining a durable response at the time of analysis. Durability of response seemed to vary according to the underlying disease and/or disease severity. The actuarial event-free survival (EFS) at 60 months is 10.6% for SLE, 31% for MS, 42.1% for MG, 50% for AIHA, 33% for pemphigus, and 25% for the other diseases. Interestingly, disease activity improved from pre-HD CY in virtually all patients even at the time of relapse, as many patients became responsive to immunosuppressive agents that were previously ineffective in controlling their disease. Discussion HD CY with or without HSCT has a potent disease modifying effect in wide variety of autoimmune disorders. These data suggest that eliminating HSCT after HD CY maintains both its efficacy and safety. The duration of cytopenias compares favorably with HSCT, especially when factoring in the mobilization phase of HSCT. Furthermore, eliminating mobilization and HSCT may have at least theoretical advantages in that the overall duration of the procedure is shortened, any toxicity associated with mobilization is avoided, and the potential of reinfusing autoreactive lymphocytes with the autograft is averted. Disclosures Jones: Accentia: Patents & Royalties. Brodsky:Accentia: Patents & Royalties." @default.
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• W2536103419 date "2009-11-20" @default.
• W2536103419 modified "2023-09-29" @default.
• W2536103419 title "High Dose Cyclophosphamide (HD CY) without Hematopoietic Stem Cell Transplantation (HSCT) in Refractory Severe Autoimmune Diseases: 11 Year Experience in Over 100 Patients." @default.
• W2536103419 doi "https://doi.org/10.1182/blood.v114.22.3412.3412" @default.
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