Primary myelofibrosis: own experience and news from diagnostic and treatment

The newest advances in primary myelofibrosis (PMF) pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features) issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors) trials results are discussed.</p

Primary myelofibrosis: own experience and news from diagnostic and treatment

The newest advances in primary myelofibrosis (PMF) pathogenesis study, diagnostic and treatment approaches are presented in this article. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of PMF, it caused by JAK2, CALR, MPL genes mutations. Authors demonstrate their own data about epidemiology, clinical signs, diagnostic and treatment results of 315 PMF patients. The most frequent clinical symptoms are: anemia, leukocytosis, thrombocytosis, splenomegaly, constitutional symptoms. Diagnostic criteria, prognostic scales (including cytogenetic and molecular features) issues are reviewed. Intermediate-1 risk grade is in the most proportion of patients. Therecommended PMF treatment algorithm is listed. The treatment methods, target drugs (Janus kinases inhibitors) trials results are discussed

All we know about polycythemia vera: literature review and own experience

The literature review and own long-term polycythemia vera diagnosis and treatment experience are presented in this article. The results of newest advances in pathogenesis description, modern diagnostic techniques and treatment modalities in polycythemia vera are included. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of polycythemia vera. In this case this activation caused almost exlusively by JAK2 gene mutations. Authors demonstrate their own data about epidemiology, clinical signs and diagnostic and treatment results of 252 polycythemia vera patients. The most frequent clinical symptoms at diagnosis were: plethora, headache and dizziness, fatigue, pruritus. Diagnostic criteria and thrombotic complications prognostic scale are presented. The thrombosis frequency in this polycythemia vera patients group was 11.1 %. It was included 3.6 % of myocardial infarctions and 5.2 % of strokes. The thrombotic complications rates statistically differed in various prognostic groups. For example, from 2.6 % in low-risk group to 20.6 % in high-risk thrombosis group. The used personalized polycythemia vera management algorithm is listed. The treatment methods features, target drugs (Janus kinases inhibitors) trials results are discussed

Dasatinib: ten years of clinical practice worldwide

The article contains results of meta-analysis of experience in use of second-generation tyrosine kinase inhibitors – dasatinib. The results of clinical trials dasatinib therapy in chronic myelogenous leukemia imatinib-resistant or intolerant patients are presented. The dasatinib and imatinib comparative analysis in first-line therapy in newly diagnosed chronic myelogenous leukemia patients are demonstrated. The range and frequency of dasatinib therapy adverse events are analyzed. Toxicities management recommendations are listed. Perspectives of dasatinib therapy cessation in patients with long lasting deep molecular responses – treatment free chronic myelogenous leukemia remissions are descripted. Also, there is an information about dasatinib usage in treatment of Philadelphia-positive acute lymphoblastic leukemia

Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kinase inhibitors was performed. The average direct cost for one patient and total budget impact in twenty years were calculated. Analysis was made based on costs of original imatinib and generics. We used the imatinib generics’ substitution experience as a scenario for the second generation TKIs. Under these conditions, more frequent therapy cessation with second generation TKIs resulted in nilotinib first line is cost saving over imatinib. We should note that theresults of our analysis were strongly dependent on the input parameters values. The Pharmacoeconomic modelling can forecast the budget burden and its future dynamics on the individual and national level. The results of such modelling could be of value in decision-making in national guidelines development and discussion with healthcare authorities.</p

Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kinase inhibitors was performed. The average direct cost for one patient and total budget impact in twenty years were calculated. Analysis was made based on costs of original imatinib and generics. We used the imatinib generics’ substitution experience as a scenario for the second generation TKIs. Under these conditions, more frequent therapy cessation with second generation TKIs resulted in nilotinib first line is cost saving over imatinib. We should note that theresults of our analysis were strongly dependent on the input parameters values. The Pharmacoeconomic modelling can forecast the budget burden and its future dynamics on the individual and national level. The results of such modelling could be of value in decision-making in national guidelines development and discussion with healthcare authorities

Combination therapy with ruxolitinib plus low-dose cytarabine or mercaptopurine in patients with blast-phase myelofibrosis

Patients with myelofibrosis in blast-phase commonly have a median overall survival of only 3–6 months. Given the older median age of onset and heavy pretreatment, intensive chemotherapy often is not appropriate and has low efficacy with high toxicity. Ruxolitinib (a JAK1/2 inhibitor) has provided significant clinical benefits in patients with chronic phase myelofibrosis. We report our experience of treating blastphase myelofibrosis patients with the combination therapy of ruxolitinib plus low dose mercaptopurine or low-dose cytarabine. The cases presented here demonstrated the feasibility and tolerability of combination continuous ruxolitinib treatment with mercaptopurine or low-dose cytarabine for patients with blast-phase myelofibrosis. The efficacy of these combination regimens is encouraging

Tyrosine kinase inhibitors therapy related neutropenia and thrombocythopenia correction in CML patients

At present, introduction of target therapy to chronic myelogenous leukemia (CML) treatment made CML not life-limiting disorder. The main condition of treatment efficacy is its continuity. The most common causes of dose reduction and CML therapy interruption is hematologic toxicities such as neutropenia and thrombocytopenia. The adverse events correction in these circumstances is vital. Recommendations for neutropenia and thrombocytopenia correction are proposed in this article. The basement and results of the use of granulocyte colony stimulating factor (G-CSF) and thrombopoietine receptor agonist for hematologic toxicities correction with clinical case are presented.</p