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  • 1
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e23759a8-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2922183-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4452-4452
    Abstract: Abstract 4452 Imatinib (IM) is now used world-wide as a first line chronic myeloid leukemia (CML) treatment. Although some time lack may exist between diagnosis and IM treatment. Earlier (Blood 2009, 114: Abstract 4278) we have shown that in CML chronic phase (CP) pts with very long history of the disease(more than five years)the pretreatment by Busulfan was the adverse prognostic factor on Imatinib therapy. Now we extend our study by a population of pts recently and for rather short time pretreated by busulfan. Aim. To investigate the effect of busulfan pretreatment on survival and responses to imatinib in CML pts in late CML CP. Materials and methods. In retrospective study 85 pts with CML CP from St-Petersburg, Leningrad region (Russian Federation) and several Ukrainian centers were included. The main inclusion criteria were: CML late CP (the duration of the disease more than 6 mos before IM start), IM therapy in routine clinical practice at least 12 months. The median time of IM therapy was 42,9 mos (12–97 mos), the median age of pts at the IM start was 49,5 years (19–83), male/female ratio 31/54. 23 patients were pretreated with busulfan (the study group) and 62 were not (control group). These groups were equal by age, sex, the median time from diagnosis to the IM start (28,3 mos in the study group and 23,9 in the control group), Sokal risk groups. Median time of busulfan pretreatment was 3,9 mos (1–62 mos). Statistical analysis was performed with SPSS 17. Results. In the whole group of patients frequency of complete cytogenetic response (CCyR) was 60% (51/85), estimated overall survival (OS) by 5 years from IM start was 87% (death rate 7% - 6/85). In the study group CCyR rate was significantly lower, than in the control group: 34,8% (8/23) and 69,35% (43/62), respectively, p=0,038. Estimated OS by 5 years was 72% (death rate 17% - 4/23) for busulfan-pretreated pts and 95% (death rate 3% - 2/62) for the control group, p 〈 0,01. Interestingly, that in the group of shortly busulfan-pretreated pts (the duration of pretreatment ≤6 mos), the lower CCyR rate has also been observed – 31% (4/13), although all other parameters were seemed equal to the control group (median time before IM start 28,3 mos). Conclusion. The pretreatment with busulfan impaired negatively the efficacy of imatinib treatment in CML late CP patients. Even short pretreatment (less than 6 mos) had adverse effect on CCyR. The mechanism is unclear. Busulfan pretreatment before imatinib therapy should not be used. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4476-4476
    Abstract: Abstract 4476 At present, the main goal of chronic myeloid leukemia (CML) therapy is to obtain complete cytogenetic response (CCyR) which is strongly associated with patient's survival. The second main factor for good prognosis after CCyR achievement is its stability. The aim of this study was to reveal factors, influencing the stability of CCyR in CML chronic phase (CML-CP) patients on Imatinib (IM) therapy in routine clinical practice. Patients and methods: In patients database of St-Petersburg and Leningrad region there are 235 CML-CP patients, who received IM for 12 months or more. Eligibility criteria for analysis were as follow: IM start dosage 400 mg/day, CCyR, which was confirmed by at least 2 consecutive cytogenetic analysis with 0% Ph+ cells in at least 20 metaphases. Patients in CCyR with IM therapy interruptions more than 3 months were censored at the date of last cytogenetic analysis. Results: 115 patients from our database were found to eligible for analysis. The median age at the diagnosis was 48 years (16-76 years). Male/female ratio was 50/65. The median time from diagnosis to IM treatment was 7 months (0.1-108 months), 55 patients begun the IM treatment in early CML-CP (≤ 6 months since diagnosis). 64, 38 and 13 patients had low, intermediate and high Sokal scores respectively. There were no differences between patients in early and late CML-CP. 56 (48,7%) patients before IM were treated with interferon. The median observation time on IM treatment was 56 months (16-88 months). Overall estimated probability of CCyR loss was 16%, rate 12.1% (14/115). In 10 patients CCyR was lost within major CyR. The estimated overall survival (all causes of death) was 78% (death rate 4.3% (5/115)), and only 1 death was CML-related. The probability of CCyR loss was not depend on previous interferon therapy and was equal in both groups -16%. The rate of CCyR loss was 15.3% (9/59) vs 8.9% (5/56) in pts with or without interferon pretreatment respectively. Sokal scores also didn't influence CCyR stability: CCyR loss rates were 10.9% (7/64), 13.2% (5/38), 15.4% (2/13) for low, intermediate and high risks, respectively (p 〉 0.1). Probabilities of CCyR loss in different ages groups were similar: 13% (rate 8% (4/50)) vs 18% (rate 15.4% (10/65)) in patients older and younger than 50 years old, respectively (p 〉 0.1). CCyR loss was less frequent in early CML-CP 10% (rate 3.6% (2/55)) then in late CML-CP 21% (20% (12/60)), p=0.032. For more thoroughly analysis, patients in late CML-CP were divided in subgroups related to duration of CML before IM initiation: 〉 6 and ≤12 months, 〉 12 and ≤60 and more than 60 months. Probabilities of CCyR loss in this groups were 22% (rate 20% (3/15)), 27% (rate 25.7% (9/35)) and 0% (rate 0% (0/10)), respectively (p 〈 0.05). The median time to CCyR loss was 29.5 months in early CP, 10.3 months in group 6–12 months before IM, and 14.2 months in 12–60 months before IM group (p 〈 0.01). Probability of CCyR loss was correlated with time to its achievement. CCyR was lost in 10% (rate 8.9% (7/78) of patients with CCyR obtained within 12 months of IM treatment with counterpart of 28% (18.9% (7/37)) for late-responders (CCyR after 12 months IM), p=0.02. The further subdivision by the time to CCyR achievement did not reveal any significant differences. Among patients, who lost CCyR, only 2/14 (14%) patients progressed to blast crisis. One of them was treated with chemotherapy followed by allo-SCT. At present, he is still alive in CCyR and complete molecular response. Another patient with blast transformation was treated by high dose IM with chemotherapy. There is no response and patient died due to progressive disease. From other patients: CCyR was re-obtained in 7 patients - in 5 patients on IM (2 pts on the same dose and 3 pts after IM dose escalation) and in 2 pts on second generation TKIs. One patient after IM dose escalation is not yet evaluable. Other 3 patients didn't respond either high dose IM or second generation TKIs, but are still alive in CML-CP. One patient lost from follow up. Conclusions: Patients in CML-CP with CCyR has very good prognosis. Very few patients progressed and dead during several years. There are two factors, which influence the probability of CCyR loss: initiation of IM in early CP and CCyR in first year of treatment are favorable to good prognosis for CCyR durability. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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    detail.hit.zdb_id: 80069-7
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  • 4
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 20 ( 2020-09), p. S242-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2540998-0
    detail.hit.zdb_id: 2193618-3
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  • 5
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-16)
    Abstract: Tyrosine kinase inhibitor (TKI) therapy has greatly improved the prognosis of patients with chronic myeloid leukemia (CML), improving the survival expectancy of patients with chronic phase (CP) CML to that of the general population. However, despite these advances, nearly 50% of patients with CP CML experience failure to respond to frontline therapy, and most fail to respond to the subsequent second-line TKI. Treatment guidelines for patients failing second-line therapy are lacking. This study aimed to determine the efficacy of TKIs as third-line therapy in a “real-world” clinical practice setting and identify factors favorably influencing the long-term outcomes of therapy. Methods We have retrospectively analyzed the medical records of 100 patients with CP CML. Results The median age of the patients was 51 (range, 21–88) years, and 36% of the patients were men. The median duration of the third-line TKI therapy was 22 (range, 1– 147) months. Overall, the rate of achieving complete cytogenetic response (CCyR) was 35%. Among the four patient groups with different levels of responses at baseline, the best results were achieved in the groups with any CyR at the baseline of third-line therapy. Thus, СCyR was reached in all 15 and 8/ 16 (50%) patients with partial cytogenetic response (PCyR) or minimal or minor CyR (mmCyR), respectively, whereas CCyR was detected only in 12/69 (17%) patients without any CyR at baseline (p & lt; 0.001). Univariate regression analysis revealed that the factors negatively associated with CCyR achievement in thirdline TKI therapy were the absence of any CyR on first- or second-line TKI therapy (p & lt; 0.001), absence of CHR prior to third-line TKI (p = 0.003), and absence of any CyR prior to third-line TKI (p & lt; 0.001). During the median observation time from treatment initiation to the last visit [56 (4–180) months], 27% of cases progressed into accelerated phase or blast phase CML, and 32% of patients died. Discussion Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with CCyR on third-line than in the group without CCyR on third-line therapy. At the last visit, third-line TKI therapy was ongoing in 18% of patients, with a median time of treatment exposure of 58 (range, 6–140) months; 83% of these patients had stable and durable CCyR, suggesting that patients without CHR at baseline and without CCyR at least by 12 months on third-line TKI should be candidates for allogeneic stem cell transplantation, third-generation TKIs, or experimental therapies.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 6
    In: Neuron, Elsevier BV, Vol. 109, No. 3 ( 2021-02), p. 448-460.e4
    Type of Medium: Online Resource
    ISSN: 0896-6273
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2001944-0
    SSG: 12
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  • 7
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 24-24
    Abstract: Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associated with HIV. Despite improved understanding of this disease, its prognosis remains poor with short overall survival. There is no standard of care for this entity. Recent advances in the treatment of HIV-associated and aggressive lymphomas have not yet significantly improved the outcomes of patients with PbL. Methods We investigate epidemiological characteristics and the results of the treatment of the HIV-related PbL in large cohort of HIV-related lymphoma patients for a 7-year period (2014-2020). During the observation period, 22 cases of HIV-related PbL were registered in three centers and selected for the analysis from the national multicenter retrospective study database. The median follow-up was 17,8 (4-57,4) months. Results The PbL accounted for 8,9% of lymphomas in HIV-infected patients (22/247). The median age was 42 years (32-61), males - 9 (41%). Most of the patients (n=19, 86%) had III-IV stages and B-symptoms were present in 8 patients (36%). CNS involvement was diagnosed in 8 patients (36%). The median of ECOG score was I (I-III). Half of patients had viral hepatitis as a co-infection including HCV (n=9), HCV and HBV (n=1), HCV, HBV and HDV (n=1). HIV and lymphoma were diagnosed simultaneously in 7 patients (32%). Median time from HIV infection to the lymphoma onset was 4 years (1,5 month - 17,5 years). The only one patient did not receive cART for an unknown reason. The median number of CD4+ cells at the moment of chemotherapy (CT) started was 151 cell/mcl (13 - 374). Frontline CT were following: CHOP±E - 9 (41%), EPOCH - 11 (50%), hyper-CVAD - 1 (4,5%), dexamethasone - 1 (4,5%). Bortezomib was added to frontline treatment in 3 (13,6%) patients, HDC with auto-HSCT had been done as a first line therapy in 2 (9%) patients. A total of 16 patients responded to the first line therapy with the overall response rate (ORR) of 72,7% including CR and PR in 4 (18,2%) and 12 (54,5%) patients respectively. Remaining patients had progression disease (n=5, 22,8%) and stable disease (n=1, 4,5%). The median course to achieve the ORR was 4 (2-6) cycles. Overall (OS) and progression-free survival (PFS) at 2 years after first line treatment was 59,1% and 40,9%, respectively. The median time to progression (TTP) was 7,95 (0,33-23,93) months. The addition of bortezomib and auto-HSCT in first line chemo improved OS (100% vs 47,1%, p=0,027), but non PFS (p=0,1) and TTP (p=0,4). Nine patients received second-line CT: DHAP - 4 (44,4%), ICE - 4 (44,4%), EPOCH - 1 (11,2%). Response was evaluated in 8 patients. CR, PR and progression disease was registered in 1 (12,5%), 2 (25%) and 5 (62,5%) patients respectively. PBSC harvesting was only successful in 1 of 3 cases (33%) and this patient received HDC with auto-HSCT. OS and PFS at 2 years after second line treatment was 44,4% and 22,2%, respectively. Two years after second line CT, 4 patients were still alive, including those after ICE, EPOCH (n=2), HDC with auto-HSCT (n=1) and nivolumab (27 cycles) as a third line therapy (n=1). Conclusions In a large cohort of patients PbL accounted for 8.9% of all HIV-related lymphomas. Bortezomib-containing chemotherapy and first line auto-HSCT show encouraging results, but data are obtained in a small group of patients. Prospective studies are needed for optimization of HIV-related plasmablastic lymphoma therapy. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: The is early clinical date on efficiency of Bortezomib in patients with plasmablastic lymphoma: https://doi.org/10.1111/bjh.15156
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4432-4432
    Abstract: Abstract 4432 Background: The incidence of chronic myeloid leukemia (CML), reported from some population based registries, varies significantly. CML is known as age-dependent disease, so population age structure may strongly influent on the data. For international comparisons several systems for age-standardization are using in epidemiological studies. We conducted our retrospective study to reveal differences in CML incidence rates on the basis of calculation – crude or age-adjusted according to different population standards in St. Petersburg and Leningrad region. Methods: In 2005 the database of Ph- and/or bcr-abl- positive CML patients (pts) was conducted in St. Petersburg and Leningrad region. Since then the data from all newly diagnosed CML patients were included prospectively on population basis. The database was updated at least bi-annually. The data were obtained from hematologists, as general practitioners and private physicians are not licensed to treat oncohematological disorders. The data were double checked from the list of Imatinib distribution (the only drug reimbursed for first line treatment). To calculate crude CML incidence rate we use the data of the general census of the population in Russia in 2010 (the whole population of our region is 6596434 with population in age 15 and above 5821133). For age-adjusted CML incidence rate we use three of currently existing standards: The Segi (“World”), The Scandinavian (“European”) and the WHO standard (based on world average population between 2000–2025). Results: There are 258 (242 in chronic, 9 in accelerated and 7 in blastic phases) CML adult (15 years and above) pts, registered during 2006–2011. The median age is 53 years (48,5 and 55,5 years for men and women respectively). Sokal score was evaluable in 209 pts. It is low in 37%, intermediate in 35% and high in 28% pts. The crude CML incidence rate is slightly higher in men than in women with ratio 1,2:1. Mean annual crude CML incidence rate was 0,65 per 100 000 whole population of Saint Petersburg and Leningrad region, but it was 0,74 in adult population (15 years old and above). Mean annual CML incidence rates in the same age groups were slightly higher in all three standardized systems: 0,94 in Segi, 0,84 in Scandinavian and 0,88 in WHO standard populations. CML incidence rates in all age groups are presented in the table 1. CML incidence rate was lowest in young pts. It was unexpectedly very low in senior pts. CML incidence rates nearly for all age groups were slightly higher in St. Petersburg than in the Leningrad region. The majority of pts (98%) were treated with Imatinib (93% first or second line) or other tyrosine kinase inhibitors (5% first line-in international clinical trials, 18% after Imatinib failure or intolerance). Stem cell transplantation was performed only in 8/258 (3%) pts. Only 25235 (7,5%) evaluable pts progressed from chronic to advanced phases. Only 29/258 (11%) pts dead mostly due to CML (21 CML related deaths were reported). Estimated 5 years overall survival is 91,5%. Mean annual overall CML pts death rate was 1,9% (mean annual death rate between 2006–2010 in whole population of our region was 1,6%). Mean pts accumulated very fast - annual CML prevalence increasing rate between 2005–2011 was more than 14% (Picture 1). Conclusions: CML incidence both crude and age-adjusted in our population based registry is nearly the same in young and middle age, but much lower in senior (65 years and above) pts groups in comparison with published data from other registries which probably represents peculiarities of health system rather than real incidence. In the tyrosine kinase inhibitors era CML patients death rate is very low (nearly the same as in whole population) and CML pts is accumulated very fast in our region. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 34 ( 2017-08-22), p. 56030-56040
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 10
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4288-4288
    Abstract: Abstract 4288 Resistance to imatinib could be overcome by new generations of TKIs. Data about the efficacy of second line TKI treatment may help to create a system for prognosing the duration of 2nd line TKI treatment and time of switching from second line TKI treatment to hematopoietic stem cell transplantation. The aim of the study was to evaluate the results of 2nd line TKI treatment in patients resistant or intolerant to imatinib. Patients and methods 44 resistant and 3 intolerant to imatinib pts were included. Cytogenetics with G-banding and PCR with sequencing were performed for evaluation the response and mutations. There were 39, 7 and 1 pts in CP, AP and BP respectively, Patients were treated by three different ATP-pocket inhibitors. The follow-up on 2nd line TKIs was 0.9-48mons (Median - 15.9 mons), median follow-up from diagnosis was 73,9 mons. In prognosis analysis (CHR, cytogenetics, Sokal) intolerant patients were not included. Results Probability of overall survival from diagnosis by 10 years was 85%. Probability of survival from the start of TKI2 by 4 y -90%. There were no differences in survival in pts with primary and secondary resistance, in CP and AP. Patients with low and intermediate Sokal risk did better than patients with high risk (p=0.014, Fig. 1.). 8 pts had T315I mutation when studied on second line TKI therapy. Achievement of CCyR was 50% (58% when T3151 patients were excluded), it was higher in low+intermediate in comparison with high risk pts (60% vs 30%, p=0.091), in CP than in AP (56% vs 20%,p=0.07), in patients with CHR at switching than in those without CHR (72% vs 18%, p=0.014). We failed to find any differences in CCyR achievement in pts with different best cytogenetic response on imatinib (complete, major, minor, minimal responses, absence of cytogenetic response). MCyR depended on the type of resistance - it was higher in secondary, than in primary resistant pts (80% vs 45%,p=0.06, Fig2). Probability of MCCyR loss was 20%, all of them appear during the first year of treatment. It was higher in AP than in CP (40% vs 12%,P=0.04). Probability of 4 years PFS was high - 75%, also without differences in primary vs secondary resistance and even in AP vs CP. Conclusion Second line TKI treatment is very efficacious in imatinib resistant pts. The effect depended on the type of resistance and phase of the disease, CHR at the moment of switching to 2nd line treatment. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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