Efficacy of eculizumab in refractory life-threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia.
Ontology highlight
ABSTRACT:
SUBMITTER: Gauchy AC
PROVIDER: S-EPMC7752594 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Efficacy of eculizumab in refractory life-threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia.
Gauchy Anne-Cécile AC Hentzien Maxime M Wynckel Alain A de Marcellus Victoire V Rodier Cyrielle C Delmer Alain A Quinquenel Anne A
Clinical case reports 20200817 12
Eculizumab may be considered as an emergency therapeutic option in refractory life-threatening warm autoimmune hemolytic anemia especially if direct antiglobulin test is positive for both IgG and C3d and after failure of all conventional treatments. ...[more]
Similar Datasets
Project description:MethodsWe report the case of a 73-year-old Saudi female who presented with severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. The coexistence of published cases of two hematological disorders with brucellosis is rare.ResultsDespite the initial treatment with eltrombopag and intravenous immunoglobulin (IVIG), our patient's platelets count remained low and significantly improved after initiation of brucellosis treatment in the form of rifampicin and doxycycline. Discussion. We conclude by reviewing the case that in many parts of Saudi Arabia, brucellosis remains a prevalent infection. Hence, it should be considered as a possible diagnosis in febrile individuals with no localizing indications and the presence of severe thrombocytopenia in acute febrile illness. Although it is a rare association, it could be related to brucellosis.ConclusionThis is our region's first published case of severe thrombocytopenia and mild autoimmune hemolytic anemia associated with brucellosis. It contributes to the literature on the successful use of rifampicin and doxycycline to treat hematological disorders associated with brucellosis.
| S-EPMC9883092 | biostudies-literature
Project description:Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ? 40 ?mol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x10(9)/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.
| S-EPMC6224177 | biostudies-literature
Project description: Not available
| S-EPMC5803969 | biostudies-literature
Project description:The diagnosis of autoimmune hemolytic anemia (AIHA) can be made with a stepwise approach that aims to identify laboratory and clinical evidence of hemolysis and then determine the immune nature of hemolysis with the direct anti-globulin test. Once alternative causes for these findings have been excluded, AIHA is established, and the clinician must search for secondary causes, as well as identify the type of AIHA. Rituximab is now the preferred second-line treatment for primary warm AIHA and first-line treatment for primary cold agglutinin disease (CAD), either as monotherapy or combined with bendamustine. Complement inhibitors have shown utility in stabilizing AIHA patients with acute severe hemolysis. Future prospects are discussed and include the C1s inhibitor BIVV009 (sutimlimab) that is now entering phase 3 studies for CAD.
| S-EPMC6246027 | biostudies-literature
Project description:Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) <10 g/dL who had failed at least one prior treatment. Hemoglobin levels and safety assessments were performed at visits every 2 weeks. The primary endpoint was Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.
| S-EPMC9313871 | biostudies-literature
Project description:Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1-3 per 105 individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor-based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor-based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T- and B-cell proliferation.
| S-EPMC8933632 | biostudies-literature
Project description:Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies.
| S-EPMC7796467 | biostudies-literature
Project description:Chronic myelomonocytic leukemia is similar to but a separate entity from both myeloproliferative neoplasms and myelodysplastic syndromes, and shows either myeloproliferative or myelodysplastic features. We ask whether this distinction may have a molecular basis. We established the gene expression profiles of 39 samples of chronic myelomonocytic leukemia (including 12 CD34-positive) and 32 CD34-positive samples of myelodysplastic syndromes by using Affymetrix microarrays, and studied the status of 18 genes by Sanger sequencing and array-comparative genomic hybridization in 53 samples. Analysis of 12 mRNAS from chronic myelomonocytic leukemia established a gene expression signature of 122 probe sets differentially expressed between proliferative and dysplastic cases of chronic myelomonocytic leukemia. As compared to proliferative cases, dysplastic cases over-expressed genes involved in red blood cell biology. When applied to 32 myelodysplastic syndromes, this gene expression signature was able to discriminate refractory anemias with ring sideroblasts from refractory anemias with excess of blasts. By comparing mRNAS from these two forms of myelodysplastic syndromes we derived a second gene expression signature. This signature separated the myelodysplastic and myeloproliferative forms of chronic myelomonocytic leukemias. These results were validated using two independent gene expression data sets. We found that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators (ASXL1, RUNX1, TET2) and splicing genes (SRSF2) and the absence of mutations in signaling genes. Myelodysplastic chronic myelomonocytic leukemias and refractory anemias with ring sideroblasts share a common expression program suggesting they are part of a continuum, which is not totally explained by their similar but not, however, identical mutation spectrum.
| S-EPMC3685272 | biostudies-literature
Project description:The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.
| S-EPMC3311724 | biostudies-literature
Project description:Bortezomib is a first-in-class, potent, selective and reversible proteasome inhibitor approved for the treatment of multiple myeloma (MM) and relapsed/refractory mantle cell lymphoma. In these diseases, bortezomib targets plasma cells and lymphocytes reducing tumor burden. Recently, preclinical evidence highlighted its efficacy in reducing long-lived plasma cells responsible of autoantibodies production in several models of autoimmune conditions. These findings paved the way to a number of experiences of bortezomib use in patients with various autoimmune conditions, including autoimmune hemolytic anemia (AIHA). The latter is a nice model of autoimmunity in hematology and is caused by the production of autoantibodies against erythrocytes resulting in various degrees of hemolytic anemia. AIHA is classified in warm and cold forms according to the thermal characteristics of the autoantibody, and first-line treatment mainly relies on steroids for warm cases and the anti-CD20 rituximab for cold ones. Relapsed/refractory cases are still an unmet need, and bortezomib has been proposed in this setting with intriguing efficacy. In this review, we collected available literature on bortezomib use in AIHA and in other immune-mediated hematologic and non-hematologic diseases. Overall, most experiences highlight bortezomib efficacy even in multi-relapsed/refractory patients and suggest to consider its use in AIHA after rituximab failure.
| S-EPMC8593301 | biostudies-literature