ABSTRACT
Background: Hairy cell leukemia is a rare oncohematological disease that manifests itself in damage to the bone marrow and spleen. One of the characteristic changes in the bone marrow are large cells, a rounded nucleus and thin outgrowths - 'hairs' of the cytoplasm. The standard of care are drugs: cladribine and purine analogues-pentostatin. The complexity of therapy lies in the high risk of infections due to prolonged cytopenia during therapy. Aims: The aim of the study was to analyze the detection of hairy cell leukemia in Kazakhstan and the effectiveness of the cladribine regimen. Methods: In Kazakhstan 30 patients were diagnosed over the last 5-year period. All patients underwent cytological, histological examination of the bone marrow, bone marrow immunophenotyping. Thirty patient s were treated with cladribine intravenous infusion 0.1 mg/kg per day for 7 days. The average age was 54.6years (from 29 to 80 years), men-10, women-20. With a median follow-up of 4 years, the complete response (CR) was -25 patients, progression of disease - 3 patients, two patients die from infection. Results: Median duration of response was 38 months (range, 0.0+ to 52.0+). Median overall survival was not reached in all patients with CR. All patients had hematological complications in the form of grade 4 leukopenia - 30 patients, grade 4 thrombocytopenia - 28 patients, grade 3 thrombocytopenia - 2, patients grade 2 anemia - 9 patients. Emetic syndrome in the form of vomiting of the 3rd degree was in one patient, diarrhea of the 2nd degree in one patient. Eleven patients had febrile neutropenia. Two patients had a fatal outcome due to the development of pneumonia and subsequent sepsis. Summary/Conclusion: Treatment of patients with hairy cell leukemia with a purine analogue showed high efficiency, but was accompanied by prolonged cytopenia and frequent secondary infection. It is necessary to consider the issue of vaccination of this category of patients with anti-pneumococcal vaccine and also to conduct continuous monitoring. Ten patients with CR were vaccinated against coronavirus infection.
ABSTRACT
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, with a median age at diagnosis of approximately 70 years. The natural course of the disease varies greatly, and patients with non-progressive and asymptomatic leukemia do not require treatment. The results of CLL treatment have improved significantly in recent years, mainly due to the introduction of new, more effective drugs, including BCR inhibitors and BCL2 inhibitors. The new drugs are used continuously, while venetoclax in combination with anti-CD20 antibodies is used for 24 (rituximab) or 12 (obinutuzumab) months, depending on the type of antibody and line of therapy. The choice of treatment protocol should largely depend on the assessment of 17p deletion/TP53 mutation and immunoglobulin variable heavy chain (IGVH) mutation status, which correlate with a worse response to immunochemotherapy. The role of immunochemotherapy, which until recently was the mainstay of CLL treatment, has now significantly decreased. In the first-line, it is recommended only in patients without 17p deletion/TP53 mutation, with mutated IGVH. Other patients should receive novel targeted therapies. However, at the time of the preparation of these recommendations, these therapies are not available in the firs-line of treatment in Poland. Novel targeted therapies play a major role in the treatment of refractory/relapsed CLL, and immunochemotherapy is recommended primarily in patients with a long-term response to first-line therapy. In this article, we present an update of the guidelines for the diagnosis and treatment of CLL, including the treatment of autoimmune complications, as well as the prophylaxis and treatment of infections, developed by the Polish Society of Haematologists and Transfusiologists and PALG-CLL Working Group.
ABSTRACT
For patients with classical hairy cell leukemia (HCL) standard treatment options such as purine analogues (PA) achieve a durable response, but are associated with severe immunosuppression. In particular, PAs cause long-lasting depletion of CD4+-lymphocytes. The BRAF inhibitor vemu-rafenib is effective in HCL but its use in first line treatment is currently limited to select clinical situations such as active infection. There is a lack of clinical data on the impact of BRAF inhibitors on immune function or response to vaccines in HCL. Here, we report the use of vemurafenib in four patients with HCL during the coronavirus disease 2019 (COVID-19) pandemic with detailed immune monitoring during treatment. All patients responded to BRAFi with normalization of peripheral blood counts. None of the patients developed neutropenia or severe infection. We observed stable CD4+ and CD8+ T-lymphocyte counts while receiving vemurafenib (median treatment duration 131 days). Immunoglobulin levels were normal in all patients without decline. 3 out of 4 patients received the SARS-CoV-2 vaccination (Pfizer-BioNTech) during vemuraf-enib treatment. The IgG antibody levels against the spike-protein of SARS-CoV-2 were detectable in 3 out of 3 patients (2-12 weeks after the second vaccination). Our findings suggest that BRAF inhibitors have limited effect on cellular and humoral immune function. The findings may support the use of BRAF inhibitors during the current pandemic to avoid the potentially detrimental effects of PA and thus minimize COVID-19 related morbidity and mortality in patients without SARS-CoV-2 vaccination.