Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study

Abstract

Summary:seriously disabling, running a relapsing/remitting course which eventually becomes progressive (secondary proSeveral experimental autoimmune diseases (AID), gressive MS). In about 10-20% of cases it has a continuincluding allergic encephalomyelitis, ie the multiple ously progressive course from onset (primary progressive sclerosis (MS) model, respond to TBI and chemotherapy MS), which is slow or rapid, or even fulminant with shortfollowed by BMT. Remissions of AID may also occur ened survival. 2 There is strong evidence supporting an in patients with concomitant malignancies treated with immunopathogenic basis for the disease which could, thereallogeneic or autologous BMT. These observations have fore, be regarded as an autoimmune process directed at one emphasized the possibility of treating AID with highor other of the structural components of myelin. 3 Treatment dose therapy and haematopoietic stem cell transplaninvolves anti-inflammatory, immunosuppressive, and tation (HSCT). In a phase I/II pilot study, 15 patients immunomodulating agents, 4,5 some of which are active in with progressive MS were treated with BEAM followed managing relapses or preventing them, but none is curative. by autologous blood SCT and antithymocyte globulinMoreover, for patients with the progressive form of the dis-(ATG). Patients were severely disabled, with median ease, therapies are either unable to halt deterioration or have EDSS and SNRS scores of 6 (5-7.5) and 42 (33-62), modest effects on clinical improvement. ) and G/GMThe rationale for using haematopoietic stem cell trans-CSF (5 g/kg/day) were used for stem cell mobilization, plantation (HSCT) to treat MS is based on the principle of which caused no neurotoxicity. On days +1 and +2, ATG complete ablation of an aberrant immune system followed (2.5-5 mg/kg) was given for in vivo T cell-depletion.by reconstitution of a new immune system deriving from Allergy (93%) and infections (87%) were the principal either an allogeneic donor or a T cell-depleted autologous toxic complications. Mild, transient, neurotoxicity was transplant, as has been proposed for other autoimmune disobserved in six patients in the immediate post-transeases (AID). 12-16 Recapitulation of lymphocyte ontogeny plant period. The median follow-up time is 6 months may result in immune tolerance, especially in the allogeneic (6-18). Durable neurologic improvements have been setting in which a graft-versus-host reaction could contribdetected on both the EDSS (7/15) and SNRS (15/15) sysute to complete elimination of the patient's residual myelintems. One patient worsened at 3 months and two have reactive cells. 17 In the autologous setting it seems practirelapsed. Autologous HSCT appears feasible in MS; it cally impossible to eliminate all autoreactive cells, but the does not aggravate disability and seems to offer a clinipatient may still benefit from a strong conditioning regimen cal benefit. However, these observations need confirfollowed by a graft containing very few lymphocytes. mation and long-term ...

T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients

“…1,2 Because these cells arise from bone marrow progenitor cells, complete destruction of the immune system followed by hematopoietic progenitor (CD34 + ) cell rescue has been previously suggested or reported as therapy for multiple sclerosis. [3][4][5] The CD34 + hematopoietic stem cells will proliferate and differentiate not only into new platelets, red blood cells and neutrophils but also into lymphocytes and macrophages. In an animal model of MS, experimental autoimmune encephalomyelitis, immune ablation and syngeneic bone marrow transplantation is capable of ameliorating disease.…”

Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease

“…Only a small number of patients undergoing HSCT for an autoimmune disease have been reported [43][44][45][46][47][48][49][50][51][52][53][54] (Table 1). All were transplanted using autologous hematopoietic stem cells.…”

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

“…Além disso, especialmente para populações pobres, mas não só para elas, a descontinuidade da imunossupressão crônica, proporcionada pelo TCTH bem sucedido, representa um benefício que não pode ser medido apenas monetariamente. Por esta razão, além do Brasil (14)(15)(16)(17)(18)(21)(22) e da China (16,(38)(39)(40) , incluindo Hong-Kong (41) , outros países emergentes, como a Rússia (42) , a Hungria (43) , a Coréia do Sul (44) , a República Tcheca (45) e a Grécia (46) têm se dedicado crescentemente ao TCTH em DAI. Uma outra questão de grande importância nesta área, e ainda bastante controversa, se refere ao mecanismo de ação do transplante das células-tronco hematopoéticas nas DAI e o papel das CTH (n. o 1, Tabela 2). No transplante autó-logo, existem três explicações possíveis para este mecanismo de ação (47) : 1) efeito isolado da imunossupressão em altas doses na eliminação de linfócitos auto-reativos; neste caso, as CTH deveriam apenas prover suporte hematopoético após a imunossupressão em altas doses, reduzindo o período de pancitopenia pós-transplante; 2) as CTH poderiam restaurar a auto-tolerância a tecidos próprios, perdida na emergência DAI; ou 3) as CTH poderiam promover reparação tecidual por meio de transdiferenciação das CTH ou outras CT em células do tecido lesado pela DAI. A primeira hipótese é suportada pelo benefício clínico observado em pacientes submetidos a imunossupressão em altas doses (200 mg/kg de ciclofosfamida endovenosa) sem resgate com CTH (48)(49)(50) .…”