High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study
| Autor: | Jerry A. Molitor, Peter A. McSweeney, J. Lee Nelson, Leona Holmberg, Howard M. Shulman, Mark H. Wener, Chien-Shing Chen, Federico Viganego, Bernadette McLaughlin, Maureen D. Mayes, J. David Godwin, Muneer H. Abidi, Daniel E. Furst, Rainer Storb, Ted Gooley, Leslie J. Crofford, Gretchen Henstorf, Richard A. Nash, C. Fred LeMaistre, James R. Seibold, Kevin T. McDonagh, Keith M. Sullivan |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Cyclophosphamide medicine.medical_treatment Immunology Antigens CD34 Pilot Projects Hematopoietic stem cell transplantation Systemic scleroderma Biochemistry Gastroenterology Transplantation Autologous Scleroderma Internal medicine Granulocyte Colony-Stimulating Factor medicine Humans Survival rate Antilymphocyte Serum Skin Transplantation Scleroderma Systemic integumentary system business.industry Hematopoietic Stem Cell Transplantation Cell Biology Hematology Total body irradiation Middle Aged medicine.disease Combined Modality Therapy Fibrosis Hematopoietic Stem Cell Mobilization Surgery Granulocyte colony-stimulating factor Survival Rate Female business Immunosuppressive Agents Whole-Body Irradiation medicine.drug Follow-Up Studies |
| Zdroj: | Blood. 110(4) |
| ISSN: | 0006-4971 |
| Popis: | More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, −22.08; P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, −1.03; P < .001) at final evaluation. Importantly, for the first time, biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial. |
| Databáze: | OpenAIRE |
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