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Presentation Number: 688
Purpose: Autologous hematopoietic stem cell transplantation using a myeloablative regimen has shown promising results in the treatment of systemic sclerosis (SSc) but has been accompanied by substantial treatment related mortality (TRM) and morbidity. We have performed autologous peripheral blood stem cell (PBSC) transplantation utilizing a non-myeloablative but intense immunoablative conditioning regimen in order to reduce TRM and morbidity.
Methods: A Phase I autologous PBSC study was conducted in 10 patients with SSc and poor prognostic features. Candidates were less than 65 years old with a modified Rodnan skin score ( mRSS ) greater than 14 or a diffusion capacity less than 80%, interstitial lung disease, elevated ESR, renal involvement, or abnormal ECG. Only one patient had a mRSS less than 23 at entry into the trial. Eight of the ten patients had pre-transplant high resolution chest CT ( HRCT ) findings consistent with interstitial lung disease. Patients with severe pulmonary hypertension ( > 45 mm Hg ) were excluded. PBSC were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. The PBSC graft was cryopreserved without manipulation and reinfused after the patient was treated with a lymphoablative but non-myeloablative conditioning regimen of 200 mg/kg cyclophosphamide and 7.5 mg/kg rabbit antithymocyte globulin ( rATG ).
Results: The median number of days for neutrophil and platelet engraftment were 9 ( range 7-11 ) and 9 ( range 0-14 ), respectively. The median infused CD 34+ and CD3+ cell counts were 7.38 x 106/ kg ( range 2.35 - 14.7 ) and 2.14 x 108/ kg ( range 0.41-6.83 ), respectively. There was a marked improvement of mRSS in most of patients whereas cardiac ( ejection fraction, pulmonary artery pressure ), pulmonary function (DLCO) and renal function (creatinine) remained stable. One patient with advanced disease and poor pre-transplant performance status died 2 years after transplant in a nursing home. That patient had a normal pre-transplant HRCT and enjoyed improvement in skin score after transplant. After median follow-up of 25.5 months ( range 5-40 ), the overall survival is 90% ( nine out of ten) and progression-free survival is 70% ( seven out of ten ). Two patients had recurrence of skin thickening at 12 and 24 months respectively. One of these two patients stabilized and one improved the mRSS after initiation of mycophenylate mofitel.
Conclusions: Autologous PBSC transplantation with a non-myeloablative conditioning regimen of Cy/rATG appears safe with no TRM in our first 10 patients and no deterioration of PFTs observed in the 12 months post-transplantation. These results suggest that further evaluation of this regimen in a randomized controlled trial is warranted.
Methods: A Phase I autologous PBSC study was conducted in 10 patients with SSc and poor prognostic features. Candidates were less than 65 years old with a modified Rodnan skin score ( mRSS ) greater than 14 or a diffusion capacity less than 80%, interstitial lung disease, elevated ESR, renal involvement, or abnormal ECG. Only one patient had a mRSS less than 23 at entry into the trial. Eight of the ten patients had pre-transplant high resolution chest CT ( HRCT ) findings consistent with interstitial lung disease. Patients with severe pulmonary hypertension ( > 45 mm Hg ) were excluded. PBSC were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. The PBSC graft was cryopreserved without manipulation and reinfused after the patient was treated with a lymphoablative but non-myeloablative conditioning regimen of 200 mg/kg cyclophosphamide and 7.5 mg/kg rabbit antithymocyte globulin ( rATG ).
Results: The median number of days for neutrophil and platelet engraftment were 9 ( range 7-11 ) and 9 ( range 0-14 ), respectively. The median infused CD 34+ and CD3+ cell counts were 7.38 x 106/ kg ( range 2.35 - 14.7 ) and 2.14 x 108/ kg ( range 0.41-6.83 ), respectively. There was a marked improvement of mRSS in most of patients whereas cardiac ( ejection fraction, pulmonary artery pressure ), pulmonary function (DLCO) and renal function (creatinine) remained stable. One patient with advanced disease and poor pre-transplant performance status died 2 years after transplant in a nursing home. That patient had a normal pre-transplant HRCT and enjoyed improvement in skin score after transplant. After median follow-up of 25.5 months ( range 5-40 ), the overall survival is 90% ( nine out of ten) and progression-free survival is 70% ( seven out of ten ). Two patients had recurrence of skin thickening at 12 and 24 months respectively. One of these two patients stabilized and one improved the mRSS after initiation of mycophenylate mofitel.
Conclusions: Autologous PBSC transplantation with a non-myeloablative conditioning regimen of Cy/rATG appears safe with no TRM in our first 10 patients and no deterioration of PFTs observed in the 12 months post-transplantation. These results suggest that further evaluation of this regimen in a randomized controlled trial is warranted.
W.G. Barr, None; Y. Oyama, None; L. Statkute, None; T. Corbridge, None; K. Yaung, None; K. Quigley, None; L. Verda, None; N. Krosnjar, None; D. Bronesky, None; R.K. Burt, None.