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The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. This paper summarizes the consensus of the panel on events and major end points of interest in CML. It also focuses on specific issues concerning the intention-to-treat principle and longitudinal data analyses in the context of long-term follow-up. The panel proposes that future clinical trials follow these recommendations.

The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. This paper summarizes the consensus of the panel on events and major end points of interest in CML. It also focuses on specific issues concerning the intention-to-treat principle and longitudinal data analyses in the context of long-term follow-up. The panel proposes that future clinical trials follow these recommendations.

Abstract

No relevant conflicts of interest to declare.

The results of long-term follow-up of patients (pts) with chronic myeloid leukemia (CML) do not lose their importance. Data from routine clinical practice are of particular interest. The use of 1 st(imatinib, IM) and 2nd generation TKI (2G TKI) led to a significant increase in survival, so the probability of death associated with CML could be significantly lower than the probability of death due to common causes of death other than CML.

Chelysheva: Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Pharmstandart: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Vinogradova: Pharmstandart: Speakers Bureau; Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Lomaia: Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Pharmstandard: Honoraria. Voloshin: Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Pfizer: Consultancy; Biacad: Consultancy, Speakers Bureau. Turkina: Pharmstandart: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Novartis Pharma: Speakers Bureau.

We describe here a technique to study the clonal contribution of primitive stem cells that account for long-term hematopoiesis in the same mouse over a 14-month period. Specifically, irradiated recipient female mice were transplanted with retrovirally marked male hematopoietic progenitors. Bone marrow was then collected repeatedly from local sites from the same mice throughout a 14-month period and injected into secondary irradiated recipients for analysis of donor retrovirally marked day-11 colony-forming unit-spleen (CFU-S-11). We have tracked the temporal in vivo fate of 194 individual CFU-S–derived cell clones in 38 mice reconstituted with such retrovirally marked bone marrow cells. Our data show that long-term hematopoiesis is maintained by a large number of simultaneously functioning small, shortlived (1 to 3 months) clones that usually grow locally with little or no dispersion between different regions of the hematopoietic system. Furthermore, the clones that disappeared were never detected again. The data suggest that normal hematopoiesis is supported by the sequential recruitment of marrow repopulating cells into a differentiation mode.

No relevant conflicts of interest to declare.

Chelysheva: Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Turkina:Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Background:A success of the tyrosine kinase inhibitors (TKI) therapy in patients (pts) with chronic myeloid leukemia (CML) allowed to set a new goal: a treatment-free remission (TFR). A stable and long-lasting deep molecular response (DMR) is required for a successful TKI discontinuation. The number of CML pts with stable DMR increases on late terms of TKI therapy. With the relationship to this new goal it is relevant to evaluate the proportion of the potential candidates for TKI discontinuation in accordance with the country-specific features of the CML pts population in routine clinical practice.

Background.Ph-negative chronic myeloproliferative neoplasms (MPNs) are characterized by proliferation of one or more myeloid cell lineages and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Somatic Jak2, MPL and CALR gene mutations are responsible for more than 90% of NPM cases. These mutations affect sequential stages of prolipherative signal transduction and therefore after the emergence of one type of mutation another types basically should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases.

Introduction:Loss of heterozygosity (LOH) was described for many malignancies including leukemia. Using chromosomal microarray analysis (CMA) we have shown preliminary (Risinskaya et al. HemaSphere, 2019, V.3, No S1, P.782) that LOH in STR loci in tumor cells with the normal karyotype represents the loss of extended chromosomal areas and could be associated with uniparental disomy of the entire chromosomal arm or the entire chromosome. Uniparental disomy results not only in the elimination of the wild type allele, but also may lead to the duplication of the mutant allele of certain candidate tumor gene(s). Retrospective analysis of archival samples have shown that in most cases STR loci absent at the relapse of disease were already lost at the onset of disease. We noted LOH at STR loci is especially frequent for relapsed ALL patients and could be used as prognostic factor for possible poor clinical outcome.

Introduction.Presence of measurable by flow cytometry (FC) residual disease (MRD) is a well-known risk factor in AML patients (pts), which is associated with adverse prognosis. The main idea in MRD by FC is searching for leukemia-associated immunophenotype (LAIP) which is based on «different from normal (DfN) approach». DfN approach allows to capture any immuphenotypic (IP) shifts during the therapy. LAIP may change in 16-91% AML cases. There are some ELN recommendations for monoclonal antibodies (mAbs) which allows todetect “mandatory (most frequent)” aberrations. But each laboratory uses its own tactics for MRD detection, taking into account the capabilities and equipment, and approved standardized panel still does not yet exist.

Background

Introduction.

Chelysheva: Fusion Pharma: Other: provided consultations ; Bristol Myers Squibb: Other: provided consultations and performed lectures; Novartis: Other: provided consultations and performed lectures. Abruzzese:Pfizer: Consultancy; BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy. Rea:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Kim:BMS: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Ilyang: Research Funding. Chabaeva:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Kulikov:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.

Introduction.Minimal residual disease (MRD) detection by multicolor flow cytometry (MFC) after early induction or consolidation AML therapy is a well known factor of adverse prognosis, especially in intermediate risk group. New assessment of response in AML is complete remission with MRD-negative status. However, there is still no standardization of MFC method for AML patients (pts). Optimal time point for MRD status and its threshold value vary in different studies.

Background

Kulikov: Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.

Kulikov: Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding.

Risinskaya: Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Chabaeva:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Kulikov:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding.

Introduction and data: Social and demographic personal data are important to be included in analysis and interpretation of results of any population studies in oncology. But it looks like social status is underestimated as cofounder for survival of patients with chronic myeloid leukemia (CML). The aim of this study was to check the prognostic value of social parameters like marital status and education level in comparison with standard risk factors. Russian CML Registry include more than 10 thousand patients (pts) data. In the analysis 8326 CML pts in chronic phase (CP) with first line TKI therapy were included: 91% of pts were treated by Imatinib and 9% by other TKIs. Mean age was 49years, 4607 f/ 3705 m. Me of follow-up-4.24years. Overall survival(OS) was estimated starting the diagnosis date, event was death from any reason, date of last contact was censored for alive pts. Survival analysis was performed by SAS procedures. Results:Firstly, we perform one-way survival analysis and estimate OS depending upon the 3 parameters Sokal Score, Marital Status and Education. There are high significant dependences OS on all three factors as shown on picture 1 (OS estimates depending on values of: 1A) Sokal score (low, intermediate, high), 1B) Marital Status (married, single, widowed/divorced), 1C) Education (low/secondary, higher). Marital Status and Education are correlated with Sokal Score (corresponding Pearson's coefficients are 0.19 and 0.12, p<0.0001). This association is caused by age but is not so strong. Than we have estimate OS in each Sokal's risk groups (picture 2. OS estimates depending on Marital Status (single, married - blue line, widowed/divorced - green line) in different Sokal's risk groups: 2A) - low, 2B) - intermediate, 2C) - high). OS estimates depending on Education (picture 3; (low/secondary red line, higher- blue line) in different Sokal's risk groups: 3A) low, 3B) intermediate, 3C) high. And we see that Marital Status and Education are predictive in each risk group but the most influent in high risk group. Marital Status and Education are correlated with other impotent cofounder- age. It should be checked in additional multi factor analysis we plan to do. We also run the proportional risk regression Cox's model on this data. Hazard ratio (HR) and significance (Px2) for included parameters are following: Sokal score - HR=1.59, Px2<0.0001; Education- HR=1.76, Px2<0.0001; Marital Status- HR=1.40, Px2<0.0006. Conclusions: The social and demographic personal data should be included in any analysis of CML population data. Marital Status and Educationare obviously associated with adherence behavior of CML patients and must influent on longitude therapy output. The highly education level is favorable factor, widowed/divorced marital status is unfavorable factor for OS prognosis.

No relevant conflicts of interest to declare.

Introduction

Introduction: Loss of heterozygosity (LOH) was described for many forms of cancer including leukemia. LOH may contribute to oncogenesis through the deletion of tumor suppressor genes due to appropriate allelic loss. LOH in short tandem repeats loci (STR) has been reported for solid tumors and is widely used as malignant cells population marker. It should be noted that little is known yet about possible loss of one of certain homozygous alleles in tumour cells and STR analysis might be a promising approach to investigate this phenomenon. STR analysis is used as a routine test for chimerism monitoring after bone marrow transplantation. It could not also be excluded that recipient's chimerism estimation may be distorted in some cases due to LOH issues.

Actuality: FL3 is a heterogeneous group of follicular lymphomas. Detailed morphological, immunophenotypic and genetic characteristics of FL3 allow to explain clinical heterogeneity of the disease and to develop differentiated therapeutic approaches.

Background

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No relevant conflicts of interest to declare.

Introduction.Primary immune thrombocytopenia is a rare disease1. The incidence of ITP is not well estimated in Russia and worldwide. In adults it varies from 1,6 to 3,9/100 000 person-years2-3. The gender and age-associated results are discussed and differ in several investigations4-6.

Introduction

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No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Introduction

Aim. To evaluate late nephrotoxicity of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL).

Aim.To evaluate late cardiotoxicity of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphoma (DLBCL).

Acute myelogenous leukemia (AML) is the most sensitive to natural killer (NK)-cell reactivity among blood malignancies treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Function of NK cells is regulated by their inhibitory and activating surface receptors, including killer-cell immunoglobulin-like receptors (KIRs). KIRs with specificity to different HLA class I-encoded ligands seem to play a major role in allorecognition: HLA-C allotypes with asparagine at position 80 (HLA-C1ligands) are recognized by KIR2DL2/3, HLA-C allotypes with lysine at position 80 (HLA-C2 ligands) are recognized by KIR2DL1and KIR2DS1, and HLA-B allotypes with a polymorphic sequence motif at position 77-83 (Bw4 ligands) are recognized by KIR3DL1.There are numerous but sometimes contradictory data about the role of KIRgenes and genes of their HLAligands in outcomes after HLA-identical related and HLA-matched unrelated HCST in patients with AML.

No relevant conflicts of interest to declare.

Introduction:Detection of bone marrow involvement (BM) is a factor of poor prognosis for diffuse large B-cell lymphoma (DLBCL), since DLBCL BM is characterized by aggressive course and low response level to standard chemotherapy (CT), and 5-year overall survival (OS) rate for this group is less than 30% after ÑHOP-like CT. Intensification of therapy in this group of patients can improve the results, except patients with bone marrow involvement at diagnosis. Bone marrow involvement is a poor prognostic factor for patients treated with high-dose chemotherapy.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.