Results: Serum OPG concentrations increased throughout the study period (p = 7.26x10 -5 ) while RANKL concentrations did not change (p = 0.19). The OPG:RANKL ratio exhibited a 6.2-fold increase between Days 1 and 5. CTX-1 concentrations were lower (p = 0.006) 30 minutes after the 50 U/kg FVIII infusion. CTX-1 response for each participant was assessed using linear regression throughout the time course. Spine L1-L4 Z-score (SZ) and Hip Total Z-score (HTZ) correlate with CTX-1 response (p = 3.4x10 -4 and 0.014, respectively). The mean age of participants was 25.2 ± 2.1 at time of first study visit. Participants had a mean SZ of −0.74 ± 0.34, HTZ of −0.17 ± 0.32, Hip Neck Z-score (HNZ) of −0.16 ± 0.35, and HJHS of 20 ± 5. HTZ and HNZ decreased significantly with patient age (p = 0.027 and 0.032) while SZ and HJHS did not (p = 0.18 and 0.16). Consequently, age correction was applied to BMD comparisons. Statistical comparisons between HAL, EQ-5D-3L, and BHQ answers, BMD data, and HJHS are shown in Table 1. Summary/Conclusion: This prospective study demonstrates a relationship between FVIII deficiency and bone disease in PwH. OPG acts as a decoy ligand to RANKL, inhibiting osteoclastic bone resorption. The observed increase in OPG:RANKL ratio suggests FVIII has a direct impact on this pathway. Decreased CTX-1 concentrations following factor infusion and correlations between CTX-1 response and BMD further suggests that FVIII plays a role in moderating bone remodeling. Hemophilia-associated bone and joint pathology is associated with decreased quality of life. Correlations between BMD and questionnaire responses demonstrate that poor bone and joint health is physically limiting, causes discomfort, and negatively impacts perceptions of personal well-being. Furthermore, correlations between BMD and HJHS and ISTH-BAT responses (Table 1) illustrate a relationship between bleeding management and skeletal health. PwH with lower BMD report more nose and gum bleeds, suggesting a link between FVIII replacement and skeletal health. Bleeds in the extremities were not correlated with decreased BMD or increased HJHS, but abdominal (stomach, iliopsoas) and other bleeds were. Analysis of these data is ongoing.

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

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Background. Since 2018 a widespread national project “Healthcare” has been implemented in the Russian Federation (RF) to improve the quality, efficiency, availability, and affordability of medical care in the profiles of specialties in constituent entities of the RF. Modern hematology as a medical field of high technology and crucial solutions is notable for its multi- and interdisciplinarity of most nosological forms, complexity of diagnostic process, multi-structuredness and diversity of related physician teams in different structural units and subdivisions. One of the key issues in federal proj ects is to determine the indicators for assessing the efficiency of regional hematological services in constituent entities of the RF. Aim. To elaborate and substantiate a new integrated operational efficiency index for hematological services in constituent entities of the RF. Materials & Methods. The analysis of data and assessment of feasibility of a new integrated operational index “early mortality in acute leukemia” (AL) were based on the results of 5 multi-center trials, including an epidemiological one. Results. Multi-center clinical studies on AL are the only objective tools for assessing the treatment efficacy, its improvement, and further training of hematologists taking part in the trials. AL treatment requires well-developed infrastructure of hematological services involving not only staff matters and organization of hematologists’ activities, but also management of many highly important related subdivisions and laboratories, logistics of their interaction, time specifications, meeting clinical guidelines, and lastly, and most importantly, financial support. Conclusion. The Unified State Information System “Hematology” is the only platform providing the objective information on patients’ vital status and enabling the use of the suggested integrated index for assessing the quality and efficiency of hematological services in the regions of the RF. This indicator of early mortality in AL patients less than 60 years of age is 15 % for acute myeloid leukemias and 10 % for acute lymphoblastic leukemias. Its low values would demonstrate that this or that constituent entity of the RF is provided with sufficient infrastructure, technologies, and a professional team to keep those patients alive who have severe but curable hematological diseases. The indicator of long-term survival or “life years gained” should become the main strategic criterion for the therapy efficacy in hematological diseases.

Measurable residual disease (MRD) is a well-known independent prognostic factor in acute leukemias, and multicolor flow cytometry (MFC) is widely used to detect MRD. MFC is able not only to enumerate MRD accurately but also to describe an antigen expression profile of residual blast cells. However, the relationship between MRD immunophenotype and patient survival probability has not yet been studied. We determined the prognostic impact of MRD immunophenotype in adults with B-cell acute lymphoblastic leukemia (B-ALL). In a multicenter study RALL-2016 (NCT03462095), 267 patients were enrolled from 2016 to 2022. MRD was assessed at the end of induction (day 70) in 94 patients with B-ALL by six- or 10-color flow cytometry in the bone marrow specimens. The 4 year relapse-free survival (RFS) was lower in MRD-positive B-ALL patients [37% vs. 78% (p < 0.0001)]. The absence of CD10, positive expression of CD38, and high expression of CD58 on MRD cells worsened the 4 year RFS [19% vs. 51% (p = 0.004), 0% vs. 51% (p < 0.0001), and 21% vs. 40% (p = 0.02), respectively]. The MRD immunophenotype is associated with RFS and could be an additional prognostic factor for B-ALL patients.