Treatment of Autoimmune Disease by Intense Immunosuppressive Conditioning and Autologous Hematopoietic Stem Cell Transplantation

Abstract

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34+progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34+ selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/μL (0.5 × 109/L) and a nontransfused platelet count greater than 20,000/μL (20 × 109/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell–depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation

“…ANN NEUROL 2013;73:341-354 P owerful chemotherapy regimens followed by bone marrow reconstitution, such as chemoablation and autologous hematopoietic stem cell transplantation (HSCT), a form of bone marrow transplantation (BMT), have been applied to patients with severe autoimmune diseases including aggressive multiple sclerosis (MS). [1][2][3][4][5][6][7][8][9][10] Associated risks of high-intensity regimens, however, preclude broader use of this approach in spite of its capacity to dramatically diminish new focal inflammatory disease activity in the central nervous system (CNS) of MS patients, who are otherwise treatment refractory. [11][12][13][14][15] Hence, elucidating the immune mechanisms underlying the therapeutic effect of high-intensity HSCT could guide development of more selective treatments with a more favorable risk/benefit profile.…”

Two‐step immunoablative treatment with autologous peripheral blood CD34+ cell transplantation in an 8‐year‐old boy with autoimmune haemolytic anaemia

“…It seems that at least part of the principal effect of this treatment is as a result of the lymphoablative effect of the high-dose chemotherapy. If the chemotherapy is not sufficiently lymphoablative, persistent lymphocytes could represent a potential source of relapse (Burt et al, 1998). The role of post-transplant immunosuppressive treatment must also be considered.…”

Extracorporeal photochemotherapy for secondary chronic progressive multiple sclerosis: a pilot study

“…with relapsing remitting MS, partial prevention of relapses can be achieved by the use of b-interferon (8,9), whereas results are yet less convincing in progressive MS (10). Further treatment options include monoclonal antibodies (11)(12)(13) and autologous haematopoietic stem cell transplantation (14). The unpredictable course of the disease, especially in its relapsing-remitting forms, makes clinical trials very difficult to design.…”

“…There is no consensus on the treatment for chronic and progressive forms of MS (6)(7)(8)(9)(10)(11)(12)(13)(14). MS relapses can be treated with a course of high dose intravenous methylprednisolone (6).…”