Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases.

OBJECTIVE: High-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (AHSCT) can be a salvage therapy for patients with severe, refractory systemic autoimmune diseases. The function of the newly rebuilt immune system is important, but little is known about immune reconstitution after AHSCT in autoimmune disorders. Our aim was to investigate the repopulation of different lymphocyte subsets in patients with systemic autoimmune diseases after AHSCT. METHODS: Twelve patients with severe refractory, autoimmune diseases were enrolled in the study: four with rheumatoid arthritis (RA), four with systemic sclerosis (SSc), three with systemic lupus erythematosus (SLE), and one with autoimmune overlap syndrome (myositis and RA). After stem-cell mobilization, CD34+ apheresis was carried out, followed by conditioning and AHSCT. After transplantation, peripheral lymphocyte subsets were regularly assessed by flow cytometry. RESULTS: The follow-up time was 24 months. The overall transplantation-related mortality (TRM) was 16.7% and the transplant-related toxicity was 33% 2 years after AHSCT. Regarding the immune reconstitution, CD56+ natural killer (NK) cells appeared in the earliest phase after transplantation, followed by CD8+ T cells. B cells and CD4+ T cells became normal within 150 days. The ratio of naive cells was low 30 days after AHSCT; however, naive B cells regenerated within 2 months whereas the repopulation of naive T cells took longer. After a short increase, the ratio of memory cells decreased 2 months after transplantation. Regulatory T (Treg) cells did not change significantly in the peritransplant period. Altogether approximately 5-6 months were required for the reconstitution of the peripheral immune network. CONCLUSIONS: AHSCT can be a salvage therapeutic modality in autoimmune patients who are refractory to other conventional therapies.

Autologous stem cell transplantation in autoimmune and rheumatic diseases: from the molecular background to clinical applications.

Autoimmune diseases have a multifactorial origin. Because of disturbances of the immune system, autoreactive T and B cells target self-antigens, leading to permanent organ damage. Despite novel therapeutic protocols, the disease course is chronic and in many instances the outcome is lethal. The efficacy of stem cell therapy has been observed in autoimmune animal models and in autoimmune diseases related to haematological abnormalities. Although the therapy is more than 30 years old, its broad spread has been delayed by the serious side-effects due to the conditioning treatments based on oncological protocols. Evaluation of the data of patients who have undergone autologous stem cell therapy reinforced the view that protocols used for conditioning treatments, mostly causing lymphoablation, and procedures carried out in specialist centres significantly reduced mortality, with an almost optimal therapeutical efficacy. New, multicentre investigations have been launched to compare the efficacy of various protocols. In this review, we summarize certain aspects of the molecular background of autologous stem cell transplantation and also depict the response to therapy in various autoimmune and rheumatic diseases.

Aspects of B-cell non-Hodgkin's lymphoma development: a transition from immune-reactivity to malignancy.

The development of B-cell lymphomas is an intricate interplay among various pathogenic factors, leading to a multi-step process, encompassing various stages of B-cell maturation. Besides genetic abnormalities, a variety of environmental and microbial factors, as well as disproportional immune-regulatory processes lead to the malignant transformation. Yet, little is known about the exact chain of events, which lead from the physiological polyclonal B-cell activation as a response to exogenous antigens through oligoclonality to a monoclonal, uncontrolled, malignant B-cell proliferation. The aim of the present review was to summarize the potential harmful steps in the development of B-cell lymphomas, according to conventional and novel theories, and to depict therapeutic regimens presently in use as well as to envision future drug developments, beneficial in the battle against this lymphoid malignancy.

Antibodies against extractable nuclear antigen in non-Hodgkin lymphoma patients.

Autoantibodies are found at higher frequency in malignant lymphoproliferative diseases and also the association of these diseases with autoimmunity is documented. However precise mechanisms are not yet understood beyond these findings. We measured anti-extractable nuclear antigen (ENA) antibodies in non-Hodgkin's lymphoma patients before, during and after chemotherapy and compared these values to healthy controls. Sixty six lymphoma patients' data were compared with 30 healthy patients' data. ENA levels were significantly elevated in untreated lymphoma patients compared with healthy controls (1.85 U/l versus 0.68 U/l, P < 0.05). This increase could be observed during and after treatment as well. Those patients who responded well to initial chemotherapy were demonstrated with gradually increasing ENA antibody titers compared with the rest of patients, where a gradual decrease in titer was found. These findings are not yet statistically significant, but may help us further understand immunological reactions beyond the treatment of malignant lymphomas.

Diagnostics and treatment of pulmonary BALT lymphoma: a report on four cases.

Bronchus-associated lymphoid tissue (BALT) is a lymphoid aggregate located in the submucosal area of bronchioles and plays a central role in airway mucosal immunity by inducing the accumulation of secretory IgA-producing cells. Long-lasting antigen stimuli promote the hyperplasia of BALT, which may develop into pulmonary mucosa-associated lymphoma (baltoma). Most pulmonary lymphomas are low-grade B-cell lymphomas. We have recently treated four patients with BALT lymphoma and this is our first report on their diagnostics and treatment. Based on these cases we wanted to demonstrate the difficulties of differential diagnosis during bronchoscopic and computed tomography (CT) examinations as well as the pitfalls of thoracosurgical vs hemato-oncological treatments.

[Hematopoietic stem cell transplantation in the treatment of autoimmune diseases]. / Haematopoeticus óssejt-transzplantáció alkalmazása az autoimmun kórképek kezelésében.

Stem cell transplantation is a new possibility to treat autoimmune diseases. Animal data and early clinical trials highlight that rebuilding the completely destroyed immune system leads to the remission of several immune-mediated diseases. The aim of this review was to summarize experimental and clinical results as well as recommendations for the protocol of stem cell transplantation and its complications.