Chronic Myeloid Leukemia in a Patient with Previous Idiopathic Thrombocytopenic Purpura: How to Manage Imatinib Together with Eltrombopag

The occurrence of chronic myeloid leukemia (CML), or other myeloproliferative diseases, after the development of idiopathic thrombocytopenic purpura (ITP) is very rare in the current medical literature. Considering the advances in ITP management, and the wide use of new drugs for ITP and CML, we report an unusual case with this association. Our case report focused on a 64-year-old man with long-standing ITP treated with eltrombopag, who developed hyperleukocytosis during follow-up; after specific laboratory exams, it was diagnosed as CML and he began treatment with imatinib. The treatment with eltrombopag was balanced with imatinib to stabilize his platelet count. Data on bcr-abl and JAK2 transcripts were collected and revealed an optimal response with the achievement of negativization of both molecular signatures. We could demonstrate that treatment with imatinib and eltrombopag was well tolerated and allowed complete molecular remission of CML to be achieved, as well as of ITP.

Polycythemia vera as a rare cause of hypertension in a young man

Polycythemia vera (PV) is an orphan haematological disease and one of the most common myeloproliferative diseases, with the incidence rate of about 0.4–2.8 cases per 100 000 population per year. In patients, proliferation of all three haematopoietic lineages is observed, typically with the development of erythrocytosis. As a rule, PV occurs in patients aged 60–70 years, slightly more often in men. The main clinical signs of PV are weakness, significant burning sensation in fingers and palms due to the increased blood viscosity and microcirculation disorders, discomfort in the left hypochondrium due to splenomegaly at the background of extramedullary haematopoietic sites development, as well as gross vascular complications (thrombosis) of various localisation. Our clinical case represents a rare cardiac manifestation of the PV in a young man.

HSCT FOR CHRONIC MYELOPROLIFERATIVE DISEASES

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

P2X7 Receptor in Hematological Malignancies

The P2X7 receptor is an ion channel gated by the nucleotide ATP, known for its role in immune responses and recently emerging as a critical onco-promoting factor. Lymphocytes, myeloid cells, and their precursors were among the first cells proved to express a functional P2X7 receptor; therefore, it is not surprising that lymphoproliferative and myeloproliferative diseases, also known as hematological malignancies, were shown to be related in their insurgence and progression to P2X7 alterations. Here, we overview established and recent literature relating P2X7 with the biological mechanisms underlying leukemias, lymphomas, and multiple myeloma development. Particular attention is paid to studies published in the very recent past correlating P2X7 with ATP concentration in the leukemic microenvironment and P2X7 overexpression to acute myeloid leukemia aggressiveness and response to chemotherapy. The described literature strongly suggests that P2X7 and its genetic variants could be regarded as potential new biomarkers in hematological malignancies and that both P2X7 antagonists and agonists could emerge as new therapeutic tools alone or in combination with traditional chemotherapy.

Assessing risks of developing myeloproliferative diseases complications with laser doppler flowmetry

Public healthcare in Russia faces many challenges; meeting them requires non-standard and innovative approaches. The set tasks are being solved within the «Public healthcare development» State program. A sub-program within it is called «Development and implementation of innovative diagnostics, prevention, and treatment procedures as well as basics of personified medicine». This sub-program involves wide use of information and digital technologies. Personified medicine envisages developing such methods that would allow early detection of a probable disease even at a preliminary stage in examining a patient; this detection is to be based on a simple and relatively cheap diagnostic technology and to provide a medical center with reliable data on detected signs of a disease for a further diagnosis. Mass use of such technologies also requires truly reliable mathematic procedures and models for putting a preliminary diagnosis. At present cardiovascular diseases are still the leading cause of death all over the world; they develop due to variable factors including influence exerted by malignant neoplasms and also due to chemotherapy. The paper contains data collected by contemporary medical experts on case histories and complications of myeloproliferative diseases caused by vascular system pathology that holds the first rank place as per mortality worldwide. It was detected that both pathological cellular mass and medications applied to treat myeloproliferative neoplasms could produce adverse effects on vascular endothelium damage to which plays the leading role in cardiovascular continuum. To assess risks of myeloproliferative diseases complications, we examined patients using Laser Doppler Flowmetry (LDF). The results were processed with a logistic regression model. As per ROC-analysis results the obtained diagnostic criterion has sensitivity (1 – β) and specificity, (1 – α) that are equal to 0.87 and 0.96 accordingly, and it means diagnostics is high-quality. The procedure and the mode can be applied in digital medicine.

Assessing risks of developing myeloproliferative diseases complications with laser doppler flowmetry

Public healthcare in Russia faces many challenges; meeting them requires non-standard and innovative approaches. The set tasks are being solved within the «Public healthcare development» State program. A sub-program within it is called «Development and implementation of innovative diagnostics, prevention, and treatment procedures as well as basics of personified medicine». This sub-program involves wide use of information and digital technologies. Personified medicine envisages developing such methods that would allow early detection of a probable disease even at a preliminary stage in examining a patient; this detection is to be based on a simple and relatively cheap diagnostic technology and to provide a medical center with reliable data on detected signs of a disease for a further diagnosis. Mass use of such technologies also requires truly reliable mathematic procedures and models for putting a preliminary diagnosis. At present cardiovascular diseases are still the leading cause of death all over the world; they develop due to variable factors including influence exerted by malignant neoplasms and also due to chemotherapy. The paper contains data collected by contemporary medical experts on case histories and complications of myeloproliferative diseases caused by vascular system pathology that holds the first rank place as per mortality worldwide. It was detected that both pathological cellular mass and medications applied to treat myeloproliferative neoplasms could produce adverse effects on vascular endothelium damage to which plays the leading role in cardiovascular continuum. To assess risks of myeloproliferative diseases complications, we examined patients using Laser Doppler Flowmetry (LDF). The results were processed with a logistic regression model. As per ROC-analysis results the obtained diagnostic criterion has sensitivity (1 – β) and specificity, (1 – α) that are equal to 0.87 and 0.96 accordingly, and it means diagnostics is high-quality. The procedure and the mode can be applied in digital medicine.

Immunotherapy in Myeloproliferative Diseases

Myeloproliferative diseases, including myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), are driven by genetic abnormalities and increased inflammatory signaling and are at high risk to transform into acute myeloid leukemia (AML). Myeloid-derived suppressor cells were reported to enhance leukemia immune escape by suppressing an effective anti-tumor immune response. MPNs are a potentially immunogenic disease as shown by their response to interferon-α treatment and allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Novel immunotherapeutic approaches such as immune checkpoint inhibition, tumor vaccination, or cellular therapies using target-specific lymphocytes have so far not shown strong therapeutic efficacy. Potential reasons could be the pro-inflammatory and immunosuppressive microenvironment in the bone marrow of patients with MPN, driving tumor immune escape. In this review, we discuss the biology of MPNs with respect to the pro-inflammatory milieu in the bone marrow (BM) and potential immunotherapeutic approaches.

Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which is often caused by recurrent emboli. These are also frequently found in patients with myeloproliferative diseases. While myeloproliferative diseases can be caused by gene defects, the genetic predisposition to CTEPH is largely unexplored. Therefore, the objective of this study was to analyse these genes and further genes involved in pulmonary hypertension in CTEPH patients. A systematic screening was conducted for pathogenic variants using a gene panel based on next generation sequencing. CTEPH was diagnosed according to current guidelines. In this study, out of 40 CTEPH patients 4 (10%) carried pathogenic variants. One patient had a nonsense variant (c.2071A>T p.Lys691*) in the BMPR2 gene and three further patients carried the same pathogenic variant (missense variant, c.1849G>T p.Val617Phe) in the Janus kinase 2 (JAK2) gene. The latter led to a myeloproliferative disease in each patient. The prevalence of this JAK2 variant was significantly higher than expected (p < 0.0001). CTEPH patients may have a genetic predisposition more often than previously thought. The predisposition for myeloproliferative diseases could be an additional risk factor for CTEPH development. Thus, clinical screening for myeloproliferative diseases and genetic testing may be considered also for CTEPH patients.