IMMUNE CYTOPENIAS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (PECULIARITIES, PROGNOSTIC MARKERS)

Background: Immune cytopenia (IC) is one of the major complications in chronic lymphocytic leukemia (CLL). The paper describes the peculiarities of different immune cytopenia in CLL patients and the importance of individual prognostic markers in the course of the disease. Methods: We observed 62 patients with CLL complicated by immune cytopenia. Among these patients 30 had autoimmune hemolytic anemia (AIHA), 18 experienced immune thrombocytopenia (ITP), 10 had Fisher-Evans syndrome (FES), 3 were diagnosed with partial red cell aplasia (PRCA), and immune neutropenia (IN) was revealed in 1 patient. In addition to general examination and laboratory studies, the following examinations were performed: immunophenotyping of peripheral blood lymphocytes, flow cytometry (CD5; CD19; CD20; CD23; CD38; ZAP70), Coombs test, a molecular cytogenetic study of peripheral blood lymphocytes using the FISH method with TP53 and ATM probes, the level of ß2-microglobulin. Results: It was established that the overall survival of CLL patients with IC depends on the form of the latter. The median overall survival in patients with Fisher-Evans syndrome was the shortest (75 months), slightly better survival was observed in patients with AIHA (median 80 months), the best survival was found in patients with ITP (median not reached). Among unfavorable markers of CLL with IC, there is the presence of del 11q22.3. Unfavorable prognostic markers were also the following: a positive Coombs test, high levels of ZAP 70 expression, and high levels of ß2-microglobulin

Anemia hemolitik otoimun dengan immune thrombocytopenia

Latar belakang Sindroma evan (Evans syndrome) merupakan penyakit yang sangat jarang, dimana terjadi suatu keadaan anemia hemolitik otoimun yang bersamaan dengan immune thrombocytopenia (ITP). Penyakit ini diperkenalkan pertama kali pada tahun 1951 oleh Evan dkk Kasus Seorang laki-laki pegawai toko 23 tahun datang dengan keluhan cepat lelah dan perdarahan gusi hilang timbul selama 4 bulan terakhir.Laboratorium hemoglobin 4,8 gr%, trombosit 11.900 /mm, leukosit 11.090/mmk, retikulosit yaitu 12,4 %. Pada pemeriksaan gambaran darah tepi ditemukan sferosit pada eritrosit dan giant trombosit. Ureum, kreatinin, natrium, kalium, kalsium normal . Protein total 8,4 gr/dl albumin 3,2 gr/dl. Didapatkan hiperbilirubinemia (4,48 mg/dl) dengan dominasi bilirubin indirek (2,20 mg/dl). Didapatkan peningkatan dari kadar ANA sebesar 79 U, tetapi anti Ds-DNA tidak meningkat (201,9 U). Pemeriksaan coomb pada penderita ini menunjukkan hasil yang positif baik direk (+3) maupun indirek (+2).Selanjutnya pasien diberikan injeksi intravena metilprednisolon 125 mg/12 jam dan siklosporin oral 50 mg/12 jam selama 5 hari dilanjutkan pemberian metilprednisolon dan siklosporin oral sampai pasien pulang dan selama dirumah. Kesimpulan Anemia hemolitik otoimun dan immune thrombocytopenia yang terjadi bersamaan (sindroma Evan) merupakan kelainan yang jarang dijumpai. Penegakan diagnosis disertai dengan menyingkirkan penyebab anemia dan trombositopenia imun sekunder yang lain. Pemberian steroid dan imunosupresan pada sebagian besar pasien masih menunjukkan hasil yang cukup baik dalam mencapai keadaan remisi.

A full-term pregnant woman with secondary Evans syndrome caused by severe coronavirus disease 2019: a case report

Background In this report, we describe a very challenging case of a patient with secondary Evans syndrome caused by severe coronavirus disease 2019 infection in a pregnant full-term woman. Case presentation A 29-year-old full-term pregnant Indonesian woman presented with gross hematuria, dry cough, fever, dyspnea, nausea, anosmia, and fatigue 5 days after confirmation of coronavirus disease 2019 infection. Laboratory examinations showed very severe thrombocytopenia, increased indirect bilirubin, and a positive direct Coombs’ test. From peripheral blood, there was an increased number of spherocytes, which indicated an autoimmune hemolytic process. Antinuclear antibody and anti-double-stranded DNA test results were negative, and her virology serological markers are also negative for human immunodeficiency virus, cytomegalovirus, and hepatitis B and C. Despite aggressive treatment with platelet transfusion, high-dose steroid, and thrombopoietin receptor agonists, the platelet count did not recover, and a speculative cesarean delivery had to be done with a very low platelet count.

Primary Evans syndrome in an adult man

Evans syndrome (ES) is a simultaneous or subsequent development of two haematological disorders, autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP). It can be primary (idiopathic) or secondary (associated with an underlying disease). Primary Evans is a diagnosis of exclusion and has a poorer prognosis than AIHA or ITP alone. We present a 55-year-old man who presented with weakness and lethargy and was diagnosed to be suffering from primary ES.

Severe neonatal autoimmune thrombocytopenia secondary to maternal Evans syndrome

Evans syndrome is a rare and chronic autoimmune disease seen in both paediatric and adult age groups. We present a case of severe thrombocytopenia in a neonate born to a mother with Evans syndrome who showed no response to intravenous immunoglobulin therapy initially and improved after treatment with methylprednisolone.

Autoimmune Cytopenias and Covid-19 Vaccination: Relapse and Suggested Treatment

Introduction: There are "de novo" and relapsed autoimmune diseases in patients with COVID-19 that includes autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia among others (Hematology 2021;26:225-239 and Curr Rheumatol Rev 2021;17:193-204). There is scanty material about relapse of autoimmune hematological diseases after vaccination for COVID-19 (Blood Adv 2021;13:2794-2798). Material and methods: Adult patients 18 years or older with autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia who completed SARS-Cov2 vaccination. Results: Between December 2020 and June 2021 there were identified 53 patients with autoimmune hematological disease that completed SARS-Cov2 vaccination. Thirty-six with autoimmune thrombocytopenia, all were preexisting. Twelve with autoimmune hemolytic anemia, 5 secondaries to previous COVID-19 and 7 preexisting. Five with Evans syndrome, all preexisting. Twenty-three patients with autoimmune thrombocytopenia did not develop any fall in the platelet count. Ten patients had a fall of 50 % from basal counts and recovered spontaneously. Three patients developed counts below 30,000 with purpuric symptoms and needed treatment that consisted in two courses of dexamethasone 40 mg daily for four days every three weeks; all patients reached complete remission without any further treatment. All patients with Evans syndrome developed hemolysis and low platelet counts. Two patients maintained Hb levels above 10 and platelet counts above 50,000; both patients had spontaneously recovery. Three patients developed Hb levels below 7 with anemic syndrome and platelets below 50,000 but without purpuric syndrome; they received the same treatment as patients with autoimmune thrombocytopenia and reached complete remission too. All five patients with autoimmune hemolytic anemia secondary to COVID-19 developed Hb levels below 7 with anemic symptoms and needed treatment as described. The remaining 7 patients with preexisting autoimmune anemia developed hemolysis; five with Hb levels above 7 and recovery without any treatment; two had Hb levels below 7 and received the same treatment with full recovery and complete remission. Conclusions: Autoimmune cytopenias can be trigger by vaccines and viral infections by involving molecular mimicry and circulating immune complexes, including SARS-Cov2. The viral protein spike from SARS-Cov2 has mimicry between the Ankyrin-1 in the erythrocyte surface, and has been linked as one of the pathogenesis pathways of autoimmune hemolytic anemia secondary to COVID-19 (Br J Haematol 2020;190:e92-e93 and Blood 2020;136:suppl8,138001). Relapse of autoimmune cytopenias after vaccination with SARS-Cov2 involves stimulation of autoantibodies production from preexisting B cells. Although relapses were observed in the three kinds of patients, all with hemolytic component developed a drop in the hemoglobin levels, most of them needed treatment. It is important to notice that patients with hemolytic autoimmune anemia secondary COVID-19 had severe relapse, event that support the mimicry mentioned lines above. It is important to follow up closely this kind of patients after SARS-CoV2 vaccination, we suggest weekly complete blood counts, and a short courses of high dose dexamethasone can induce curable responses if treatment is advised. Disclosures No relevant conflicts of interest to declare.

Genetic Screening of Patients with Evans Syndrome: A Single Centre Analysis

Background: Evans syndrome (ES) is a rare disorder defined as the simultaneous or sequential presence of autoimmune haemolytic anemia and immune thrombocytopenia but it can also be considered as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying congenital immune dysregulation syndrome that, in some case, can benefit from specific treatments. Aims: The aim of this study is to investigate the clinical/immnunological characteristics and the underlying genetic background of a single centre cohort of patients with ES. Methods: Data were obtained from a retrospective charts' review of patients with a diagnosis of ES in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both hematologic and immunological disorders as congenital bone marrow failure syndromes, primary immunodeficiencies, and primary immune regulatory disorders. Results: Fourteen patients (23 males, 17 females) with a median age at onset of 6 years (range 0-16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine/40 (8%) patients had a family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 29/40 (72%) of cases, respectively. Seventeen out of 40 (42%) children fitted the ALPS diagnostic criteria. The remaining 15 (37%) and 9 (22%) were classified as having an ALPS-like phenotype and an isolated ES, respectively. Twenty patients (50%) were found to have an underlying genetic defect on TNFRSF13B, FAS, CTLA4, IKBGK, CARD11, LIG4, LRBA, STAT3, CASP10 and ADA2 genes. Table 1 shows the details of clinical/immunological characteristics of patients with or without a genetic diagnosis. No significant differences were noted between the two groups. Conclusions: This study shows that half of patients with ES have a genetic background, secondary to Primary Immunodeficiencies. Therefore, an immunological screening and an extended molecular evaluation should be offered to all patients, since specific genetic diagnosis may benefit from targeted treatments. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.