Mobilization, harvesting and selection of peripheral blood stem cells in patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation

Abstract

Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens.

Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis

“…The reason for collection and re-infusion of PBSC in this study is to shorten the duration of CY-induced neutropenia and thus decrease the risk of infection. 11 Our data suggest that a non-myeloablative transplant regimen may have less adverse effects than was seen in a myeloablative regimen containing TBI while producing similar skin score (mRSS) improvement. However, this is a controversial area and only time will prove the superiority of one regimen over another.…”

“…10 Following a non-myeloablative regimen, re-infusion of HSC is not necessary for hematopoietic reconstitution but is performed as a safety measure to shorten the duration of neutropenia induced by the conditioning regimen. 11 After HSCT using a TBI-based myeloablative conditioning regimen, the efficacy data in terms of modified Rodnan skin score (mRSS) appear promising; 6,8,9 however, substantial treatment-related toxicity including mortality and treatment-related deterioration of internal organ (lung and kidney) function and radiation-related myelodysplastic syndrome/leukemia has tempered enthusiasm for this approach. 9,10,12 In contrast, non-myeloablative non-radiation containing autologous HSCT regimens have been utilized to treat safely both systemic lupus erythematosus 13 and type I diabetes mellitus.…”

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

“…Mobilization is associated with flair of AID and bacteremia caused by severe cytopenias, leading to increased morbidity and mortality. 15,[63][64][65][66][67] In addition, with autologous HCT, there is a risk of relapse from reinfusion of autoreactive lymphocytes. Although many patients with malignancies have been treated by allogeneic HCT, autologous HCT has been favored over allogeneic HCT for treatment of AID because of the increased risks of morbidity and mortality from GVHD.…”

Mobilization and harvesting of PBPC in newly diagnosed type 1 diabetes mellitus

“…5,6 The same cannot be asserted for patients with T1DM. Herein, we found that all 25 patients with T1DM had an efficient CD34 þ cell mobilization with CY and G-CSF, demonstrated by the high concentration and the early peak of CD34 þ cells in the peripheral blood.…”

“…6 Patients with systemic lupus erythematosus achieved the lowest CD34 þ number in peripheral blood and the lowest cell yield, whereas patients with multiple sclerosis or scleroderma achieved the highest. Furthermore, Statkute et al, 5 had to perform a mean of 1.8 apheresis sessions per patient with CAID (2.5 for those with lupus). Overall, patients with T1DM needed approximately half the apheresis sessions relative to patients with other autoimmune diseases, possibly because T1DM patients were 'healthier' than patients with CAID.…”