Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura with a positive direct anti-human globulin test. It is classified as primary and secondary, with the frequency in patients with autoimmune hemolytic anemia being 37%–73%. It predominates in children, mainly due to primary immunodeficiencies or autoimmune lymphoproliferative syndrome. ES during pregnancy is associated with high fetal morbidity, including severe hemolysis and intracranial bleeding with neurological sequelae and death. The clinical presentation can include fatigue, pallor, jaundice and mucosal bleeding, with remissions and exacerbations during the person’s lifetime, and acute manifestations as catastrophic bleeding and massive hemolysis. Recent molecular theories explaining the physiopathology of ES include deficiencies of CTLA-4, LRBA, TPP2 and a decreased CD4/CD8 ratio. As in other autoimmune cytopenias, there is no established evidence-based treatment and steroids are the first-line therapy, with intravenous immunoglobulin administered as a life-saving resource in cases of severe immune thrombocytopenic purpura manifestations. Second-line treatment for refractory ES includes rituximab, mofetil mycophenolate, cyclosporine, vincristine, azathioprine, sirolimus and thrombopoietin receptor agonists. In cases unresponsive to immunosuppressive agents, hematopoietic stem cell transplantation has been successful, although it is necessary to consider its potential serious adverse effects. In conclusion, ES is a disease with a heterogeneous course that remains challenging to patients and physicians, with prospective clinical trials needed to explore potential targeted therapy to achieve an improved long-term response or even a cure.

Aim: Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA.Method: This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198.Results: A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up. Conclusion:The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA.

Key Points• Eltrombopag/dexamethasone is a safe and effective combination for treating newly diagnosed ITP patients.• This treatment may prove useful in achieving lasting responses without additional immunosuppression in some patients.Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ‡30 3

Using non-myeloablative, immunosuppressive, fludarabine (FLU)-based conditioning regimens, we have performed allogeneic peripheral blood stem cell transplants in 26 patients (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 10 with acute lymphoblastic leukemia, 1 with myelodysplasia, and 1 with thalassemia major). Conditioning consisted of FLU/busulphan/cyclophosphamide/cyclosporin-A (CyA)/ methotrexate, or FLU/melphalan/CyA/methotrexate. The median granulocyte recovery time to 0.5 × 10 9 /l was 11 days, whereas the median platelet recovery time to 20 × 10 9 /l was 12 days. Twelve patients did not need red blood cell transfusions, and 8 did not need platelet transfusions. In 21 individuals (81%), the procedure could be completed fully on an outpatient basis. Follow-up times range between 30 and 600 days: one patient failed to engraft and recovered endogenous hemopoiesis; six out of 26 patients developed acute graft-versus-host disease (GVHD) whereas 7/22 developed chronic GVHD. Twelve patients (46%) have died, nine of them with a relapsing disease and three with GVHD; median post-transplant survival (SV) was 300 days, whereas the 12-month SV was 42%. The 100-day mortality was 3.8% and the transplant-related mortality was 11.5%. This procedure is substantially less costly than its counterpart, using in-hospital myeloablative conditioning regimens, and it may represent another approach in the management of patients requiring an allogeneic stem cell transplant. Am. J. Hematol. 66:241-244, 2001.

No abstract

Treatment of autoimmune cytopenias remains unsatisfactory for patients refractory to first-line management. We evaluated the safety and efficacy of low-dose rituximab plus alemtuzumab in patients with steroidrefractory autoimmune hemolytic anemia and immune thrombocytopenic purpura. Nineteen of 21 included patients were assessable for response (11 with immune thrombocytopenic purpura, 8 with autoimmune hemolytic anemia). Treatment with 10 mg of alemtuzumab subcutaneously on days 1 to 3, plus 100 mg of rituximab intravenously weekly in 4 doses, was administered. The overall response rate was 100%, with complete response in 58%. IntroductionAutoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) are characterized by antibody-mediated destruction of red blood cells and platelets; as in other autoimmune disorders, B and T lymphocytes have important roles in their pathogenesis. 1 Corticosteroids are the standard initial treatment, with a 60% response rate. Patients unresponsive to corticosteroids usually experience a complicated course and show increased morbidity and mortality rates. Splenectomy and a large number of drugs have been used as second-line therapies with variable success, without evidence that any single agent is more effective than another. 2 Rituximab effectively depletes B cells involved in the production of antibodies and has been studied as a second-line treatment for ITP at full 3-10 and low doses 11,12 ; its use in ITP has led to a median overall response rate of approximately 60%. 7,9 Alemtuzumab, a humanized IgG monoclonal antibody specific for the CD52 antigen, expressed on lymphocytes, has been used in the treatment of lymphoproliferative disorders and recently for autoimmune diseases. 13,14 Preliminary results indicate that alemtuzumab may induce responses in patients with autoimmune cytopenias. [15][16][17][18] We evaluated the safety and efficacy of low-dose rituximab plus alemtuzumab in combination therapy in patients with steroidrefractory AIHA and ITP. The rationale for combining the 2 monoclonal antibodies was their reported single-agent activity, and the possibility of a synergistic effect, based on the fact that T lymphocytes are involved in the control of expansion of immunoglobulinproducing, autoreactive B-lymphocyte clones. MethodsApproval for the study was obtained from the Ethics Committee of the School of Medicine and University Hospital of the Universidad Autónoma de Nuevo León. Eligible patients were adults with active symptomatic ITP or AIHA, who had previously received treatment with at least one line of therapy, or followed a chronic relapsing course, and who provided written informed consent. Patients were excluded if they had active bacterial or viral infection, HIV, hepatitis C virus, cytomegalovirus immunoglobulin M (CMV-IgM)-positive serology, hepatitis B surface antigen positivity, pregnancy, or concomitant malignant disease. Pretreatment assessment included complete blood, reticulocyte, lymphocyte subset counts, serum immunoglobulins, direct an...

The combination of low-dose rituximab and high-dose dexamethasone as frontline therapy for adults with primary immune thrombocytopenia was effective and had a high overall response rate and a low incidence of relapse.

Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL.