pci-32765 and Leukemia--Prolymphocytic

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 μmol/L to 125 μmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m

Topics: Acute Kidney Injury; Adenine; Aged; Cytokines; Glucocorticoids; Humans; Kidney; Leukemia, Prolymphocytic; Male; Nephritis, Interstitial; Piperidines; Protein Kinase Inhibitors; Proteinuria

Topics: Adenine; Bridged Bicyclo Compounds, Heterocyclic; Humans; Leukemia, Prolymphocytic; Piperidines; Sulfonamides

B-cell (B-PLL) and T-cell (T-PLL) prolymphocytic leukemias are rare, poor-prognosis lymphoid neoplasms with similar presentation characterized by symptomatic splenomegaly and lymphocytosis. They can be distinguished from each other and from other T- and B-cell leukemias by careful evaluation of morphology, immunophenotyping, and molecular genetics. The clinical behavior is typically aggressive, although a subset of patients may have an indolent phase of variable length. First-line therapy for T-PLL is with intravenous alemtuzumab and for B-PLL is with combination purine analog-based chemo-immunotherapy. New B-cell receptor inhibitors, such as ibrutinib and idelalisib, may have a role in the management of B-PLL, especially for the patients harboring abnormalities of TP53. Allogenic stem cell transplantation should still be considered for eligible patients and may be the only current therapy capable of delivering a cure. In the past few years, many of the molecular mechanisms underlying disease pathogenesis and progression have been revealed and are likely to lead to the development of novel targeted approaches.

Topics: Adenine; Alemtuzumab; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Disease Progression; Humans; Immunophenotyping; Immunotherapy; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell; Mutation; Piperidines; Prognosis; Purines; Pyrazoles; Pyrimidines; Quinazolinones; Recurrence; Stem Cell Transplantation; T-Lymphocytes; Treatment Outcome; Tumor Suppressor Protein p53