16 research outputs found

    Results of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and Additional Cytogenetic Abnormalities

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    Aim. To evaluate the impact of additional chromosomal aberrations on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation. Methods. Twenty-five AML patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation (10 women and 15 men, aged from 2 to 58 years; median 20.2) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. The additional cytogenetic abnormalities were found in 13 (52 %) patients before the transplantation, at that, complex karyotype with three or more chromosomal abnormalities were registered in 9 (69 %) patients. The univariate analysis showed that OS and EFS after allo-HSCT differed in patients with different characteristics such as age (p = 0.03; p = 0.0006), clinical status at transplantation (p = 0.0002; p = 0,006), donor type (p = 0.0003; p = 0.002), the interval from diagnosis of leukemia to allo-HSCT (p = 0,008, for OS only), additional cytogenetic abnormalities (p = 0.03; p = 0.009) and complex karyotype (p = 0.004; p = 0.0003), respectively. In multivariate analysis, independent predictors of OS were donor type (p = 0.01), the interval from diagnosis of leukemia to allo-HSCT (p = 0.01), and additional cytogenetic abnormalities in karyotype (p = 0.04), as well as donor type (p = 0.04) and patient’s age (p = 0.004) for EFS. Conclusion. AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation is a heterogeneous disease. The prognosis in patients with the additional cytogenetic abnormalities, especially in those with the complex karyotype, is worse both after the standard chemotherapy (i.e. before allo-HSCT), and after allo-HSCT

    Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities

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    Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), –7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (³ 18 vs. < 18 years; p = 0.01 and p = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; p = 0.1 and p = 0.008, respectively), with and without complex karyotype (СK– vs. CK+; p = 0.05 and p = 0.002, respectively), with and without monosomal karyotype (МK– vs. MK+; p = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; p = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (p = 0.02 and p = 0.01, respectively), active disease at allo-HSCT (p = 0.04 and p = 0.005, respectively), complex karyotype (p = 0.04 и p = 0.0008, respectively) and stem cell source other than bone marrow (p = 0.02 only for OS) were independent predictors of OS and EFS deterioration. Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach

    Hydrogel-based delivery of Tat-fused protein Hsp70 protects dopaminergic cells in vitro and in a mouse model of Parkinson\u2019s disease

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    Neurodegenerative disorders such as Parkinson\u2019s disease (PD) have no effective therapies. However, many promising drugs are precluded from clinical trials because of their poor brain availability. The chaperone protein Hsp70 has been reported to be effective in PD models, but its brain targeting is challenging. We developed a novel brain Hsp70 delivery system using injectable, biocompatible, and biodegradable semi-interpenetrating polymer networks of collagen (COLL) and low-molecular-weight hyaluronic acid (LMW HA) structured with gelatin particles. We produced human recombinant Hsp70-1A fused with the cell-penetrating peptide Tat (Tat-Hsp70) that was neuroprotective in vitro against the dopaminergic toxin 6-hydroxydopamine (6-OHDA). We assessed Tat-Hsp70 release from the selected COLL-LMW HA composites in vitro, observing a 95% release of loaded protein after 96 h. The release kinetics FITTED the Korsmeyer-Peppas model (regression coefficient 0.98) and the released Tat-Hsp70 remained neuroprotective for SH-SY5Y cells. Magnetic resonance imaging revealed that COLL-LMW HA composites lasted at least 96 h at the brain level, and in vivo Tat-Hsp70 release studies indicated that hydrogel presence is pivotal for a spatially focused neuroprotective effect. In an in vivo model of dopaminergic degeneration, Tat-Hsp70-loaded composites conveyed neuroprotection at both the behavioral and dopaminergic neuronal levels against the striatal injection of 6-OHDA. After the injection of Tat-Hsp70-loaded composites, mice showed a transient inflammatory response, with a decrease in GFAP and CD11b immunostaining after 7 days. Our delivery system enabled the effective brain release of Tat-Hsp70 and is ready for further improvements
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