9 research outputs found

    Sociodemographic Characteristics Of Survival In Patients With Myelodysplastic Syndrome

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    Myelodysplastic syndrome (MDS) is a heterogeneous group of acquired hematopoietic stem cell disΠΎrders characterized by ineffective hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). Due to the phenotypic diversity of MDS, survival widely varies. The purpose of the present study is to analyze the impact of some socio-demographic characteristics on the survival of patients with MDS. We analyzed 219 patients with MDS, who were admitted in the Clinic of Hematology, University Hospital "St. Marina”- Varna for a period of 10 years (2010-2020). Survival was assessed by age, sex, FAB and WHO2016 subtype and risk group defined by IPSS, IPSS-R and WPSS. There is a significantly higher survival rate in women and an inversely proportional relationship between survival and age. Patients with RAEB and RAEB-t have the lowest survival as well as patients with high and very high risk. MDS presents with significant differences in survival between subtypes, age and sex. The outcome of the disease varies according to the risk group determined by the established scales for risk stratification, and the most accurate in the prognosis is IPSS-R

    Outcome after azacitidine treatment in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia in the Clinic of Hematology at St. Marina University Hospital, Varna

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    Introduction: Hypomethylating agents have become a standard therapy for high-risk myelodysplastic syndromes (MDS) and elderly patients with acute myeloid leukemia (AML).Aim: The aim of the study was to assess the efficacy of azacitidine treatment in patients with MDS and AML followed for 18 months.Materials and Methods: Twenty-seven patients with MDS and AML treated in the Clinic of Hematology at St. Marina University Hospital, Varna were included in the study. Azacitidine was administered subcutaneously in at a dose of 75 mg/m2 for 7 days. Disease assessment was performed on Β the 3rd month, 6th month, and at progression.Results: Twenty-seven patients were analyzed. Their median age was 71.5 years. Nine had refractory anemia with excess of blasts II (RAEB II), 5 had chronic myelomonocytic leukemia II (CMML II), 1 was with unclassifiable MDS (MDS-U), and 12 with AML. The median number of administered cycles was 6 (1-19). Eleven patients completed 6 cycles of azacitidine. Partial response was achieved in 9 patients (33%) (7 MDS and 2 AML), stable disease in 8 (29%) (5 MDS and 3 AML). Progressive disease was observed in 10 patients (37%). The response correlated with the type of the disease (p=0.03), cytogenetic risk (p=0.01), and survival (p=0.000). At 18 months, 60% of MDS patients were alive compared to 41.7% in the AML group. The median time to death in the AML patient group was 2.5 months. The mean overall survival was 10.4 months (12.6 months for MDS patients and 5.4 months for AML patients).Conclusion: The therapy with azacitidine is an option for elderly patients with high-risk MDS.Β  In patients with AML a rapid progression is observed during the first two cycles with mortality rate of 58.3%

    Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia

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    Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibodymediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 Γ— 109/L in all patients, 68 Γ— 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 Γ— 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of =50 Γ— 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts =30 Γ— 109/L and =50 Γ— 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 Γ— 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals.</p

    The role of MDS-CI in the prognostic assessment of patients with myelodysplastic syndrome

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    Myelodysplastic syndrome (MDS) is a heterogeneous group of acquired hematopoietic stem cell disorders characterized by ineffective hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). The MDS comorbidity index (MDS-CI) is designed to predict the impact of comorbidities on the outcome of the disease. Π’he aim of our analysis is to assess the prognostic value of MDS-CI within the WHO prognostic scoring system (WPSS) subgroups. We applied MDS-CI in 219 patients with MDS, diagnosed and treated in the Clinic of Hematology of St. Marina University Hospital, Varna, Bulgaria between May 2010 and May 2020. WPSS was used for prognostic stratification. Statistical analysis was performed using SPSS 20. We found that the mean age of patients with MDS was 70.7 Β± 10.2 years (35–93 years). In patients with very low/low risk according to WPSS, we found significant difference in terms of survival between MDS-CI = 0 and MDS-CI > 2 (69.2 Β± 43.0 vs. 38.3 Β± 42.1 months, p < 0.001). Similar difference was found within the intermediate/very high risk groups (p < 0.001). MDS-CI adds prognostic value to the established WPSS. Combining both systems allows refining the prognostic assessment and survival of MDS patients

    Clinical, Biological and Genetic Markers in Risk Stratification in Patients with Myelodysplastic Syndrome // Клинико-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½ΠΈ ΠΈ Π³Π΅Π½Π΅Ρ‚ΠΈΡ‡Π½ΠΈ ΠΌΠ°Ρ€ΠΊΠ΅Ρ€ΠΈ Π² рисковата стратификация ΠΏΡ€ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈ с миСлодиспластичСн синдром

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    Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cytopenia, and an increased risk of transformation into acute myeloid leukaemia (AML). The risk stratification is carried out through the approved scales of the International Prognostic Scoring System (IPSS), its revised version (IPSS-R) and the World Health Organization-based scoring system (WPSS). Established risk scales do not include prognostic factors related to the patient, such as general health, comorbidities, and degree of manifestation. Comorbidities and the degree of "frailty" play a role in determining the survival of patients with MDS. The addition of comorbid indices as an additional factor to the established risk scales significantly improves the prognosis. We established the role of clinical and biological factors. Significant prognostic factors for the course of the disease are the percentage of myeloblasts in CM, haemoglobin levels, MCV platelet and leukocyte count, serum iron, LDH, cytogenetic disorders and the number and degree of dysplasia. We have shown that patients with severe comorbidities have a 50% reduced survival, regardless of age and risk group. Determining risk using the risk stratification and comorbidity scales using comorbid indices significantly improves prognostic assessment in patients with MDS. Combining them allows for more precise risk stratification and forecasting.MΠ”Π‘ Π΅ Ρ…Π΅Ρ‚Π΅Ρ€ΠΎΠ³Π΅Π½Π½Π° Π³Ρ€ΡƒΠΏΠ° ΠΎΡ‚ ΠΊΠ»ΠΎΠ½Π°Π»Π½ΠΈ заболявания Π½Π° Ρ…Π΅ΠΌΠ°Ρ‚ΠΎΠΏΠΎΠ΅Ρ‚ΠΈΡ‡Π½Π°Ρ‚Π° стволова ΠΊΠ»Π΅Ρ‚ΠΊΠ°, Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ·ΠΈΡ€Π°Ρ‰ΠΈ сС с Π½Π΅Π΅Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½Π° Ρ…Π΅ΠΌΠΎΠΏΠΎΠ΅Π·Π°, ΠΏΠ΅Ρ€ΠΈΡ„Π΅Ρ€Π½Π° цитопСния ΠΈ повишСн риск ΠΎΡ‚ трансформация Π² ΠžΠœΠ›. Рисковата стратификация сС ΠΎΡΡŠΡ‰Π΅ΡΡ‚Π²ΡΠ²Π° Ρ‡Ρ€Π΅Π· ΡƒΡ‚Π²ΡŠΡ€Π΄Π΅Π½ΠΈΡ‚Π΅ скали Π½Π° ΠΌΠ΅ΠΆΠ΄ΡƒΠ½Π°Ρ€ΠΎΠ΄Π½Π°Ρ‚Π° прогностична скоринг систСма (IPSS), Ρ€Π΅Π²ΠΈΠ·ΠΈΡ€Π°Π½Π°Ρ‚Π° ΠΉ вСрсия (IPSS-R) ΠΈ Π±Π°Π·ΠΈΡ€Π°Π½Π°Ρ‚Π° Π½Π° Π‘Π²Π΅Ρ‚ΠΎΠ²Π½Π°Ρ‚Π° Π·Π΄Ρ€Π°Π²Π½Π° организация скоринг систСма (WPSS). Π£Ρ‚Π²ΡŠΡ€Π΄Π΅Π½ΠΈΡ‚Π΅ скали Π·Π° опрСдСлянС Π½Π° риска Π½Π΅ Π²ΠΊΠ»ΡŽΡ‡Π²Π°Ρ‚ прогностичнитС Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΈ ΡΠ²ΡŠΡ€Π·Π°Π½ΠΈ с ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚Π°, ΠΊΠ°Ρ‚ΠΎ ΠΎΠ±Ρ‰ΠΎ здравословно ΡΡŠΡΡ‚ΠΎΡΠ½ΠΈΠ΅, Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ Π½Π° ΠΊΠΎΠΌΠΎΡ€Π±ΠΈΠ΄ΠΈΡ‚Π΅Ρ‚ΠΈ ΠΈ тяхната стСпСн Π½Π° изява. ΠšΠΎΠΌΠΎΡ€Π±ΠΈΠ΄ΠΈΡ‚Π΅Ρ‚ΠΈΡ‚Π΅ ΠΈ стСпСнта Π½Π° β€žΡƒΡΠ·Π²ΠΈΠΌΠΎΡΡ‚β€œ ΠΈΠΌΠ°Ρ‚ роля Π² опрСдСлянСто Π½Π° прСТивяСмостта ΠΏΡ€ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈΡ‚Π΅ с ΠœΠ”Π‘. ДобавянСто Π½Π° ΠΊΠΎΠΌΠΎΡ€Π±ΠΈΠ΄Π½ΠΈΡ‚Π΅ индСкси ΠΊΠ°Ρ‚ΠΎ Π΄ΠΎΠΏΡŠΠ»Π½ΠΈΡ‚Π΅Π»Π΅Π½ Ρ„Π°ΠΊΡ‚ΠΎΡ€ към ΡƒΡ‚Π²ΡŠΡ€Π΄Π΅Π½ΠΈΡ‚Π΅ рискови скали Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»Π½ΠΎ подобрява ΠΏΡ€ΠΎΠ³Π½ΠΎΠ·Π°Ρ‚Π°. УстановихмС ролята Π½Π° ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½ΠΈ ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ, ΠΊΠ°Ρ‚ΠΎ Π½Π°ΠΉ-голямо Π·Π½Π°Ρ‡Π΅Π½ΠΈΠ΅ Π·Π° Ρ…ΠΎΠ΄Π° Π½Π° ΠΏΡ€ΠΎΡ‚ΠΈΡ‡Π°Π½Π΅ Π½Π° заболяванСто ΠΈΠΌΠ°Ρ‚ ΠΏΡ€ΠΎΡ†Π΅Π½Ρ‚Π° Π½Π° миСлобластитС Π² КМ, Π½ΠΈΠ²Π°Ρ‚Π° Π½Π° Ρ…Π΅ΠΌΠΎΠ³Π»ΠΎΠ±ΠΈΠ½Π°, MCV тромбоцитния ΠΈ Π»Π΅Π²ΠΊΠΎΡ†ΠΈΡ‚ΠΈΡ‚Π΅ Π±Ρ€ΠΎΠΉ, сСрумното ТСлязо, Π›Π”Π₯ , Ρ†ΠΈΡ‚ΠΎΠ³Π΅Π½Π΅Ρ‚ΠΈΡ‡Π½ΠΈΡ‚Π΅ Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ ΠΈ броя ΠΈ стСпСнта Π½Π° дисплазията. Π”ΠΎΠΊΠ°Π·Π°Ρ…ΠΌΠ΅, Ρ‡Π΅ Π±ΠΎΠ»Π½ΠΈΡ‚Π΅ с Ρ‚Π΅ΠΆΠΊΠΈ Ρ„ΠΎΡ€ΠΌΠΈ Π½Π° ΠΊΠΎΠΌΠΎΡ€Π±ΠΈΠ΄ΠΈΡ‚Π΅Ρ‚ΠΈ са с 50% Π½Π°ΠΌΠ°Π»Π΅Π½Π° прСТивяСмост, нСзависимо ΠΎΡ‚ Π²ΡŠΠ·Ρ€Π°ΡΡ‚Ρ‚Π° ΠΈ рисковата Π³Ρ€ΡƒΠΏΠ°. ΠžΠΏΡ€Π΅Π΄Π΅Π»ΡΠ½Π΅Ρ‚ΠΎ Π½Π° риска Ρ‡Ρ€Π΅Π· скалитС Π·Π° стратификация Π½Π° риска ΠΈ коморбидността Ρ‡Ρ€Π΅Π· ΠΊΠΎΠΌΠΎΡ€Π±ΠΈΠ΄Π½ΠΈΡ‚Π΅ индСкси Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»Π½ΠΎ подобрява прогностичната ΠΎΡ†Π΅Π½ΠΊΠ° ΠΏΡ€ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈ с ΠœΠ”Π‘. ΠšΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€Π°Π½Π΅Ρ‚ΠΎ ΠΈΠΌ Π΄Π°Π²Π° Π²ΡŠΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡ‚ Π·Π° ΠΏΠΎ-ΠΏΡ€Π΅Ρ†ΠΈΠ·Π½ΠΎ стратифициранС Π½Π° риска ΠΈ опрСдСлянС Π½Π° ΠΏΡ€ΠΎΠ³Π½ΠΎΠ·Π°Ρ‚Π°

    Efficacy of Inotuzumab Ozogamicin plus Ponatinib Followed by Allogeneic Stem Cell Transplantation in a Patient with Relapsed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

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    Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive disease with poor outcomes. Despite the incorporation of tyrosine kinase inhibitors (TKIs) in the therapeutic strategies, patients who relapse after chemotherapy plus TKI have poor overall survival (OS) and less chance to proceed to hematopoietic stem cell transplantation (HSCT) which remains the only curative approach. Therefore, new drugs, such as antibody-targeted therapies alone or in combination with TKIs, offer new therapeutic options for those patients. However, the combination of inotuzumab plus ponatinib has limited application. We present a case of a patient affected by Ph + ALL with T315I mutation successfully treated after early relapse with inotuzumab plus ponatinib, followed by allogeneic HSCT and ponatinib maintenance

    Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia

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    Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibodymediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 Γ— 109/L in all patients, 68 Γ— 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 Γ— 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of =50 Γ— 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts =30 Γ— 109/L and =50 Γ— 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 Γ— 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals.</p

    Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia

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    BACKGROUND Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (FcΞ³ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies. METHODS In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of β‰₯50Γ—103 per cubic millimeter and an increase from baseline of β‰₯20Γ—103 per cubic millimeter without the use of rescue medication). RESULTS Sixty patients were enrolled. At baseline, the median platelet count was 15Γ—103 per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50Γ—103 per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50Γ—103 per cubic millimeter was 65%. CONCLUSIONS Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment

    Interferons at age 50: past, current and future impact on biomedicine

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    The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential
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