Impact of First- and Second-Generation Tyrosine Kinase Inhibitors on the Development of Graft-Versus-Host Disease in Individuals with Chronic Myeloid Leukemia: A Retrospective Analysis on Behalf of the Polish Adult Leukemia Group.

: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes has not been thoroughly explored. : The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD).

Immune escape of B-cell lymphoblastic leukemic cells through a lineage switch to acute myeloid leukemia.

Acute leukemia (AL) with a lineage switch (LS) is associated with poor prognosis. The predisposing factors of LS are unknown, apart from rearrangements that have been reported to be associated with LS. Herein, we present two cases and review all 104 published cases to identify risk factors for LS.

Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

Background: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group).

Objectives: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis.

The role of daratumumab in relapsed/refractory CD38 positive acute leukemias-case report on three cases with a literature review.

Primary refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and mixed phenotype myeloid/T-cell acute leukemia have dismal prognoses. New treatment approaches, preferably targeting specific leukemic aberrations to overcome resistance, are urgently needed. The bright expression of the CD38 antigen found in several cases of T-ALL led to an investigation into the role of anti-CD38 antibodies in the treatment of T-ALL.

Impact of genetic polymorphisms of drug transporters and and regulators of xenobiotic transport and metabolism and on clinical efficacy of dasatinib in chronic myeloid leukemia.

Introduction: Functional single-nucleotide polymorphisms (SNPs) in genes regulating cellular uptake, elimination, and metabolism of xenobiotics may potentially influence the outcome of chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKI). Dasatinib, a second-generation TKI, is a substrate of the ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are involved in the control of expression of and

Aim Of The Study: In this study, we assessed the impact of inherited variants in , , , and genes on dasatinib efficacy and toxicity in CML.

The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors, Treated in Poland Within the Donation Program.

Introduction: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML.

Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients.

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome.

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia.

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation.

Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin.

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort.

Colonization with multidrug-resistant bacteria increases the risk of complications and a fatal outcome after allogeneic hematopoietic cell transplantation.

Composition of the gut microbiota seems to influence early complications of allogeneic hematopoietic cell transplantation (HCT) such as bacterial infections and acute graft-versus-host disease (GVHD). In this study, we assessed the impact of colonization with multidrug-resistant bacteria (MDRB) prior to HCT and the use of antibiotics against anaerobic bacteria on the outcomes of HCT. We retrospectively analyzed the data of 120 patients who underwent HCT for hematologic disorders between 2012 and 2014.

Acquired von Willebrand Syndrome During the Course of Myelofibrosis: Analysis of 32 Cases.

Background: Identification of patients with myelofibrosis being at increased risk of acquired von Willebrand syndrome (avWS) would likely facilitate individualization of treatment and improve its outcomes.

Objectives: To determine the prevalence of avWS in patients with myelofibrosis, and to verify if individuals with and without this bleeding disorder differ in terms of their baseline clinical parameters.

Material And Methods: The study included 32 consecutive patients with myelofibrosis.

Quality of life in chronic myeloid leukaemia patients after haematopoietic cell transplantation pretreated with second-generation tyrosine kinase inhibitors.

Aim Of The Study: The majority of patients with chronic myeloid leukaemia (CML) respond to tyrosine kinase inhibitors (TKI), while allogeneic haematopoietic cell transplantation (HCT) is indicated in selected clinical situations. HCT carries the risk of severe complications, while the toxicity profile of dasatinib and nilotinib may lead to adverse reactions affecting the quality of life (QoL). We present the results of observational analysis of CML patients who underwent HCT after exposure to second-generation TKI (TKI2), with respect to their quality of life assessed comparatively after transplantation.

Prevalence of acquired von Willebrand syndrome during essential thrombocythemia: a retrospective analysis of 170 consecutive patients.

Introduction: The identification of patients with essential thrombocythemia (ET) who are at increased risk of acquired von Willebrand syndrome (AVWS) would likely facilitate individualization of treatment and improve its outcomes.

Objectives: The aim of the study was to determine the prevalence of AVWS in patients with ET and to verify whether individuals with and without this bleeding disorder differ in terms of their baseline clinical parameters.

Patients And Methods: The study included 170 consecutive patients with ET.

Factors predisposing to acquired von Willebrand syndrome during the course of polycythemia vera - retrospective analysis of 142 consecutive cases.

Introduction: The aim of this study was to verify if PV patients with and without avWS differ in terms of their baseline clinical parameters.

Material And Methods: The study included 142 consecutive patients with PV. avWS was diagnosed on the basis of abnormally low levels of von Willebrand factor and other routine tests.

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome.

Introduction: Allogeneic hematopoietic cell transplantation (HCT) was a standard therapy in chronic phase (CP) chronic myeloid leukemia (CML). As a result of the effective therapy with tyrosine kinase inhibitors (TKI), HCT was shifted to defined clinical situations. We present the results of observational prospective analysis of 28 CML patients undergoing HCT after exposure to, at least, two lines of TKI (including dasatinib and/or nilotinib), with respect to response, overall survival (OS), treatment toxicity, graft versus host disease (GVHD), and progression/relapse incidence.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma.

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012.

Activity and tolerability of nilotinib: a retrospective multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or intolerant.

Background: Nilotinib is active in imatinib-resistant and -intolerant chronic myeloid leukemia patients and was recently approved for these indications.

Methods: Data on the efficacy and safety of nilotinib treatment were collected from 2 phase 2 expanded access clinical trials with similar designs (CAMN107AIL01 and ENACT).

Results: Of 88 study patients (58 chronic, 11 accelerated, 19 blast crisis), the best responses to nilotinib were complete hematologic response (CHR) in 27%, partial cytogenetic response in 12%, complete cytogenetic response in 14%, and major molecular response in 19%.

Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

Introduction: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment.

Objectives: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM).

Patients And Methods: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months.

[No influence of imatinib on type 2 diabetes].

Five patients with type 2 diabetes, three of them treated with insulin and two with oral antidiabetic drugs, receiving imatinib due to chronic myeolid leukaemia are reported. Treatment with imatinib 400 mg/day for 7 to 37 (mean 24.2) months had no positive effect on clinical course of type 2 diabetes.

Imatinib in Philadelphia chromosome-positive chronic phase CML patients: molecular and cytogenetic response rates and prediction of clinical outcome.

Previous clinical trials with the tyrosine kinase inhibitor imatinib in chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia (CML) resulted in 95% of hematologic and 60% major cytogenetic remissions in patients who failed a previous interferon-alpha-containing regimen. In an identical clinical trial setting with 39 chronic-phase CML patients we achieved comparable cytogenetic response rates after a median follow up of 30.1 weeks, with an almost identical toxicity profile.

Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical course, prognostic indexes and survival in patients with chronic myeloid leukemia.

Background: Chronic myeloid leukemia is characterized by the presence of the Philadelphia chromosome. At the molecular level a fusion of part of the ABL and BCR genes is observed. The breakpoint locations in the BCR gene fall between exons b2a2 or b3a2 (5' and 3', respectively).