Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience

Abstract Background: In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods: This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results: Median (range) age was 35.9 (19-59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1-7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions: Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.(AU)

Trasplante de células progenitoras hematopoyéticas en enfermedades autoinmunes / Hematopoietic stem cell transplantation in autoimmune diseases

El trasplante de células progenitoras hematopoyéticas, células con capacidad de autorrenovación y reconstitución de todos los tipos de células sanguíneas, se utiliza en el tratamiento de numerosas enfermedades potencialmente letales incluyendo leucemias y linfomas. Hoy en día es posible además aplicarlo en el tratamiento de enfermedades autoinmunes graves, como esclerosis múltiple, lupus eritematoso sistémico o esclerosis sistémica, resistentes a la terapia convencional. Estudios en modelos animales nos demuestran que la transferencia de células progenitoras hematopoyéticas podría revertir el proceso de autoinmunidad, un fenómeno que puede explicarse mediante diferentes mecanismos. El resultado de los estudios clínicos que se están llevando a cabo, así como también estudios en pacientes y modelos animales, ayudarán a determinar el rol que el transplante de células progenitoras hematopoyéticas puede jugar en el tratamiento de enfermedades autoinmunes.

Transplantation of hematopoietic stem cells, which are capable of self renewal and reconstitution of all types of blood cells, can be a treatment for numerous potential lethal diseases, including leukemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant multiple sclerosis, lupus and systemic sclerosis. Studies in animal models show that the transfer of hematopoietic stem cells can reverse autoimmunity. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.

Trasplante autólogo de médula ósea como tratamiento de enfermedades autoinmunes: mecanismos y resultados / Autologous Bone Marrow Transplantation as a Treatment for Autoimmune Disease: Mechanisms and Results

Las enfermedades autoinmunes se caracterizan por una respuesta del sistema inmune del individuo hacia tejidos propios. Una línea de investigación actual es el tratamiento de estas enfermedades y el desarrollo de tolerancia. Una de las opciones en la búsqueda del desarrollo de tolerancia es el trasplante autólogo de médula ósea: la variantes del trasplante de médula ósea que hace uso de células progenitoras hematopoyéticas propias. La posibilidad de usar este tipo de trasplante como tratamiento de enfermedades autoinmunes se originó en los hallazgos de remisiones de enfermedades autoinmunes coexistentes, en pacientes que eran trasplantados por enfermedades oncológicas. En esta revisión presentemos el fundamento teórico de este tratamiento, así como una recopilación de los estudios preclínicos y clínicos más relevantes en esta materia. Aunque algún reporte inicial puso en duda la utilidad de dicho procedimiento, en general, los resultados son alentadores. Es necesario que más pacientes en diversos estadios de las enfermedades autoinmunes sean referidos a centros especializados de manera que sea posible recopilar la información de manera ordenada y sistemática, y se pueda arribar a un conocimiento sobre el papel que juega este tipo de tratamiento en las enfermedades autoinmunes.

Autoimmune diseases are characterized by immune response against self antigens. One of the current research interests in this field is oriented toward development of tolerance. One of the newest options in the search for tolerance is autologous bone marrow transpiantation: a variant of bone marrow transplant in which the patient's own hematopoietic stem cells are reinfused after myeloablative therapy. The idea of using bone marrow transplant in treatment of autoimmune diseases derived from observing remission in autoinmune diseases in patients transplanted due to coexisting neoplastic disease. Although an isolated initial report of bone marrow transplant as treatment for autoimmune disease questioned the utility of this procedure, over all, results are encouraging. To compile information in a programmed and systematic manner, it is necessary to send more patients in all stages of immune diseases to specialized centers to be included in large multicenter randomized trials. In time, the role for this procedure in autoimmune diseases will become clear.

Transplante renal e esclerose sistêmica progressiva: relato de caso e revisäo da literatura / Renal transplant and progressive systemic sclerosis: case report and literature review

Descreve-se o caso de um paciente de 55 anos portador de esclerose sistêmica progressiva que após quatro anos em hemodiálise é submetido a transplante renal com doador cadáver. A evoluçäo clínica foi turbulenta, tendo o paciente evoluído com perda da funçäo renal sugestiva de rejeiçäo. O paciente faleceu no 71§ pós-operatório, em virtude de sepsis secundária a necrose intestinal; a necrópsia revelou recidiva na nefropatia da esclerodermia. É feita revisäo do comprometimento renal na esclerodermia e dos casos de transplante renal descritos na literatura