Collection of hematopoietic stem cells from patients with autoimmune diseases

Abstract

Summary:We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 g/kg/day) or cyclophosphamide (2 or 4 g/m 2 ) with either G-CSF (5 or 10 g/kg/day) or GM-CSF (5 g/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P Ͻ 0.001). G-CSF alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and G-CSF (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell

Transplante de células-tronco hematopoéticas em doenças reumáticas. Parte 2: experiência brasileira e perspectivas futuras

“…143 x 10 3 /µl), mas também foi escolhida para futuros estudos porque induziu uma resposta clínica mais prolongada do que nos pacientes condicionados com 100 mg/kg de CY (17- 19 vs. 2-3 meses) (64) . Em estudos retrospectivos, a mobilização com G-CSF isoladamente foi menos tóxica do que a combinada com ciclofosfamida (que causou mortalidade em 2,6% dos pacientes), mas induziu maior número de reativações da doença de base (65) e regimes de condicionamento mais agressivos causaram menos recaídas pós-transplante, mas maior mortalidade (11) . Assim, a tendência atual é utilizar mobilização com ciclofosfamida em dose baixa (2 g/m 2 combinada a G-CSF) e regimes de condicionamento de intensidade reduzida, subablativos, tanto nos transplantes autólogos como nos alogênicos, evitando-se o emprego de irradiação corporal total e esquemas poliquimioterápicos mieloablativos (66,67) .…”

Normal bone marrow hematopoietic stem cell reserves and normal stromal cell function support the use of autologous stem cell transplantation in patients with multiple sclerosis

“…In particular, marginal or even failed mobilizations occurred in 9.2% of MS patients while inadequate BM progenitor cell harvests occurred in two patients. 12 Difficulties in stem cell mobilization procedure have also been described by Carreras et al 39 in 13.3% of cases in a series of 15 MS patients since one patient failed mobilization after two attempts while an additional patient reached the target CD34 þ cell yield following three leukaphereses.…”

“…[18][19][20][21][32][33][34] Studies in other autoimmune diseases have already shown abnormalities in BM hematopoiesis [7][8][9][10] capable of affecting the mobilization and/or the engraftment of stem cells in patients undergoing ASCT. [11][12][13] In the current study, we have evaluated the reserves and functional characteristics of BM hematopoietic progenitor cells and the hematopoiesis supporting capacity of BM stromal cells in MS patients and we have found that these patients displayed normal proportion of CD34 þ hematopoietic progenitor cells in the BMMC fraction and normal proportion of early CD34 þ /CD38 À and committed CD34 þ /CD38 þ cells. In contrast, the clonogenic potential of hematopoietic progenitor cells was found to be significantly reduced in these patients as was demonstrated by the low CFC number obtained from BMMCs and purified CD34 þ cells in short-term BM cultures and the low CFC recovery in NACs from LTBMCs.…”

“…Specifically, in a large survey performed by Burt et al, 12 who evaluated retrospectively data from 24 transplant centers to determine the outcome of the procedure in patients with a variety of autoimmune diseases including 76 patients with MS, it was identified that MS patients displayed low progenitor cell yields in comparison to rheumatoid arthritis or to systemic sclerosis patients. In particular, marginal or even failed mobilizations occurred in 9.2% of MS patients while inadequate BM progenitor cell harvests occurred in two patients.…”

“…For example, it has been reported that patients with active rheumatoid arthritis and systemic lupus erythematosus display a low frequency of BM CD34 þ cells and impaired hematopoiesis supporting capacity of BM stromal cells due to the presence of autoreactive cells producing pro-inflammatory cytokines and proapoptotic mediators. [7][8][9][10][11] These abnormalities may give an explanation for the recently described difficulties or failures in the stem cell collection procedure 12 and occasional graft failure 13 in some patients undergoing ASCT. In contrast, patients with primary autoimmune cytopenias exhibit increased numbers of hematopoietic progenitor cells and normal BM stromal cell function in terms of its capacity to support hematopoiesis.…”