piperidines and Anemia--Hemolytic--Autoimmune

Topics: Adenine; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunophenotyping; Incidence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Piperidines; Positron-Emission Tomography; Prevalence; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Tomography, X-Ray Computed; Treatment Outcome

In the past decade the introduction of targeted therapies has dramatically transformed the landscape of treatment for chronic lymphocytic leukemia (CLL). Whether this new therapeutic scenario will modify the current prevalence statistics and natural history of autoimmune cytopenias complicating CLL is still a matter of debate. Here we present a comprehensive review of the literature on this topic, with special emphasis on the incidence of autoimmune hemolytic anemia (AIHA). The potential to induce autoimmune cytopenia has been studied mostly with ibrutinib, a first- in-class bruton kinase (BTK) inhibitor, licensed for the treatment of relapsed/refractory high-risk CLL. Recent observations suggest that emergent AIHA occurring during therapy with ibrutinib is more an expression of CLL activity than an ibrutinib-mediated process. Since available information on AIHA occurring during and after therapy with small-molecule kinase inhibitors relies mainly on data collected from clinical trials, a close post- marketing surveillance is mandatory in order to improve our understanding of this topic.

Topics: Adenine; Anemia, Hemolytic, Autoimmune; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Molecular Targeted Therapy; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines

We present a unique case of a patient with a long-standing history of indolent chronic lymphocytic leukaemia (CLL) who suddenly developed autoimmune haemolytic anaemia after starting immune checkpoint inhibitor therapy for bladder cancer. He had no clear indication to start CLL-directed treatment based on current clinical practice guidelines; however, targeted treatment of CLL with ibrutinib proved to be effective in treating the haemolytic anaemia.

Topics: Adenine; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines

In this study, we report a case of a 77-year-old woman who was presented with anemia in the winter of 2002. She was diagnosed with cold agglutinin disease (CAD) and treated with corticosteroids. Further, her hemoglobin levels were maintained between 7.0 g/dl and 8.0 g/dl. In May 2019, mature peripheral blood lymphocytes increased with exacerbation of hemolytic anemia. The lymphocytes were positive for CD19 and CD20, but negative for CD5, CD10, and CD23. Additionally, they were positive for cell surface IgM-κ. The B-cell neoplasm could not be further subclassified due to the lack of BCL2-IgH and BCL1-IgH rearrangement and morphology. The IgM-κ-type M-protein was found in serum, and the direct Coombs test was negative for IgG but positive for C3b/C3d. These findings suggested that small B-cell neoplasm-associated M-protein was involved in the development of CAD through complement activation. Based on the presence of TP53 deletion, the patient was treated with ibrutinib monotherapy. Although hemolysis rapidly improved with a dramatic decrease in lymphocytes, she died from a cerebral hemorrhage. It is assumed that ibrutinib improved CAD through suppression of small B-cell neoplasm-related M-protein. CAD can precede lymphoproliferative disorders; however, the risk of ibrutinib-associated hemorrhage should be noted.

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Female; Humans; Lymphoproliferative Disorders; Neoplasms; Piperidines

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Red-Cell Aplasia, Pure; Steroids; Virus Diseases

Topics: Adenine; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors; Red-Cell Aplasia, Pure

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Cyanosis; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Retrospective Studies

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Cyclophosphamide; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Methylprednisolone; Piperidines; Prednisone; Pyrazoles; Pyrimidines; Recurrence; Rituximab; Salvage Therapy; Sulfonamides; Vincristine

Ibrutinib (IBR) covalently binds to the active site of Bruton's tyrosine kinase (BTK) and is used for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). Approximately 5-10% of CLL is complicated by autoimmune cytopenia (AIC), such as autoimmune hemolytic anemia (AIHA). Several cases of AIC have reportedly demonstrated improvement during IBR treatment. However, in our case, the patient developed AIHA during oral IBR treatment. As AIHA is exacerbated by the increased number of CLL cells in the peripheral blood, it may have developed because of disease progression rather than IBR use. This phenomenon may also be attributed to the production of autoantibodies due to increased number of CD5+ B cells. In this case, withdrawal of IBR and administration of rituximab improved hemolysis. If AIHA develops during treatment, its etiology must be examined to confirm the effects of treatment.

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Autoantibodies; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Pyrazoles; Pyrimidines; Rituximab

Topics: Adenine; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Clinical Trials, Phase III as Topic; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AICs). Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase approved for the treatment of relapsed CLL and CLL with del(17p). The effect of ibrutinib treatment on the incidence of AIC is currently unknown. We reviewed medical records of 301 patients treated with ibrutinib, as participants in therapeutic clinical trials at The Ohio State University Comprehensive Cancer Center between July 2010 and July 2014. Subjects were reviewed with respect to past history of AIC, and treatment-emergent AIC cases were identified. Before starting ibrutinib treatment, 26% of patients had experienced AIC. Information was available for a total of 468 patient-years of ibrutinib exposure, during which there were six cases of treatment-emergent AIC. This corresponds to an estimated incidence rate of 13 episodes for every 1000 patient-years of ibrutinib treatment. We further identified 22 patients receiving therapy for AIC at the time ibrutinib was started. Of these 22 patients, 19 were able to discontinue AIC therapy. We found that ibrutinib treatment is associated with a low rate of treatment-emergent AIC. Patients with an existing AIC have been successfully treated with ibrutinib and subsequently discontinued AIC therapy.

Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Humans; Incidence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Piperidines; Protein-Tyrosine Kinases; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Pyrimidines

Topics: Adenine; Anemia, Hemolytic, Autoimmune; Chromosome Deletion; Chromosomes, Human, Pair 17; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Recurrence; Treatment Outcome

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Remission Induction; Treatment Outcome; Waldenstrom Macroglobulinemia

Topics: Adenine; Aged; Anemia, Hemolytic, Autoimmune; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Pyrazoles; Pyrimidines