Management Of Autoimmune Cytopenias Research Articles

Evans syndrome: Disease awareness and clinical management in a nation-wide ITP-NET survey.

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.

Evans' Syndrome: From Diagnosis to Treatment.

Evans’ syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. When AIHA and ITP occurred concomitantly, the diagnosis procedure must rule out differential diagnoses such as thrombotic microangiopathies, anaemia due to bleedings complicating ITP, vitamin deficiencies, myelodysplastic syndromes, paroxysmal nocturnal haemoglobinuria, or specific conditions like HELLP when occurring during pregnancy. As for isolated auto-immune cytopenia (AIC), the determination of the primary or secondary nature of ES is important. Indeed, the association of ES with other diseases such as haematological malignancies, systemic lupus erythematosus, infections, or primary immune deficiencies can interfere with its management or alter its prognosis. Due to the rarity of the disease, the treatment of ES is mostly extrapolated from what is recommended for isolated AIC and mostly relies on corticosteroids, rituximab, splenectomy, and supportive therapies. The place for thrombopoietin receptor agonists, erythropoietin, immunosuppressants, haematopoietic cell transplantation, and thromboprophylaxis is also discussed in this review. Despite continuous progress in the management of AIC and a gradual increase in ES survival, the mortality due to ES remains higher than the ones of isolated AIC, supporting the need for an improvement in ES management.

Autoimmune Complications in Chronic Lymphocytic Leukemia in the Era of Targeted Drugs.

Autoimmune phenomena are frequently observed in patients with chronic lymphocytic leukemia (CLL) and are mainly attributable to underlying dysfunctions of the immune system. Autoimmune cytopenias (AIC) affect 4–7% of patients with CLL and mainly consist of autoimmune hemolytic anemia and immune thrombocytopenia. Although less common, non-hematological autoimmune manifestations have also been reported. Treatment of CLL associated AIC should be primarily directed against the autoimmune phenomenon, and CLL specific therapy should be reserved to refractory cases or patients with additional signs of disease progression. New targeted drugs (ibrutinib, idelalisib and venetoclax) recently entered the therapeutic armamentarium of CLL, showing excellent results in terms of efficacy and became an alternative option to standard chemo-immunotherapy for the management of CLL associated AIC. However, the possible role of these drugs in inducing or exacerbating autoimmune phenomena still needs to be elucidated. In this article, we review currently available data concerning autoimmune phenomena in patients with CLL, particularly focusing on patients treated with ibrutinib, idelalisib, or venetoclax, and we discuss the possible role of these agents in the management of AIC.

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia, and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and it involves antigen presentation by CLL cells to polyclonal B cells resulting in production of autoantibody, and alteration of the T cell milieu tilting the balance in favor of an autoimmune response. Traditional therapy of autoimmune complications in CLL consists of immunosuppression with corticosteroids and/or anti-CD20 monoclonal antibodies. In patients who have a suboptimal response, treating the underlying CLL is generally effective in ameliorating secondary cytopenias. Although novel oral therapies such as ibrutinib, idelalisib, and venetoclax have been shown to be extremely effective in the management of CLL, prospective data from larger numbers of patients with longer follow-up are needed prior to recommending their routine use in the management of autoimmune cytopenias in CLL.

Rituximab–cyclophosphamide–dexamethasone combination in management of autoimmune cytopenias associated with chronic lymphocytic leukemia

We report our experience on rituximab–cyclophosphamide–dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders in 48 patients with chronic lymphocytic leukemia (CLL). The diagnosis of autoimmune disease (AID) was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenic purpura (AITP) in nine (18.8%), Evans syndrome in eight (16.7%), and pure red cell anemia (PRCA) in five patients (10.5%). CLL was considered progressive in 40% of subjects upon AID diagnosis. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). The median duration of autoimmunity was 24 months, but the duration of response of autoimmunity (DR-AI) was higher for patients presenting with: (1) AID early during the CLL course (<3 years), or (2) both and pure red cell aplasia (PRCA) in five patients (10.5%) and AIHA.

Rituximab in Children with Autoimmune Thrombocytopenia Complicating Underlying Congenital or Acquired Immunodeficiency State.

Rituximab (chimeric anti-CD20 monoclonal antibody) has been reported to be effective in various autoimmune conditions, especially in autoimmune cytopenias, but there are few reports of its use in paediatric population with underlying immunodeficiency states. We report three cases of autoimmune cytopenias (Evan's syndrome in DiGeorge syndrome, autoimmune thrombocytopenia in a HIV positive patient and lastly autoimmune thrombocytopenia in a post liver transplant patient) where rituximab was effective in reversing the cytopenias. First patient (11yrs) had DiGeorge syndrome which was complicated by Evan's syndrome. It was treated with multiple courses of steroids and immunosuppressive agents, with resultant recurrent systemic bacterial and fungal infections. She had rituximab as a last resort, which resulted in sustained improvements in her Haemoglobin and platelet count. Second patient (12yrs) was diagnosed with HIV in 1993. She had sudden onset Intra-cranial bleed as a result of immune thrombocytopenia. She was treated with Intravenous immunoglobulin (IVIg) and subsequently with prednisolone with no response. She however responded to rituximab and then went on to have rituximab for a further 2 courses, each 12 months apart. The third patient (14yrs) had auxiliary liver transplant in 2002. He developed immune thrombocytopenia and neutropenia in which remission was sustained only for a maximum of 6 weeks following IVIg. As he was already on immunosuppression, he was given rituximab to which he has had a sustained remission. Side effects: The patient with DiGeorge syndrome had recurrent chest infection which was thought to be due to aspiration as a result of her hiatus hernia. The other patients did not have major side-effects. Immunoglobulin levels in all three patients were in normal range. Thus, in our experience rituximab is a useful adjunct in management of autoimmune cytopenias with an underlying immunodeficiency state and should be considered early in steroid refractory cases, as it leads to sustained remissions in the blood counts. It is well tolerated without major infections in patients who are already immunosuppressed due to their immunodeficiency state and the fear of immuneparesis is not seen.