[Withdrawal syndrome after tyrosine kinase inhibitors discontinuation in patients with chronic myeloid leukemia].

BACKGROUND: Withdrawal syndrome (WS) a musculoskeletal pain after discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) has been described in the treatment-free remission (TFR) studies. The pathophysiological mechanisms and predisposing factors of WS have not been well established. AIM: Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy. MATERIALS AND METHODS: WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms. RESULTS: DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1136). WS was observed in 49 (27%) patients: grade 12 was in 45 (92%) patients, grade 3 in 4 (8%) patients. Me time to WS occurrence was 2 months (range 17), Ме duration of WS was 5 months (range 135). WS was resolved in 14 of 15 patients with molecular relapse after 13 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p0.0001), longer duration of TKI therapy (p0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095). CONCLUSION: The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.

Changes in Bone Marrow Stromal Progenitor Cells in Patients with Hematoblastosis at the Onset of the Disease.

Multipotent mesenchymal stromal cells (MSC) are the key regulators of hematopoiesis. We studied changes in MSC characteristics in patients with myeloid leukemia and patients with lymphoproliferative diseases. MSC were obtained from the bone marrow of patients at the time of diagnostic puncture using a standard technique. Their proliferative potential and expression of genes associated with differentiation and regulation of hematopoiesis were studied. The total cell production of MSC in patients with leukemia at the onset of the disease did not differ from that in the group of healthy donors. The relative expression of the IL6, TGFb1 and TGFb2, PPARG genes was similar in all patients. The relative expression of the JAG1, LIF, IGF1, CSF1, IL1b, and IL1bR1 genes in MSC of patients with leukemia was enhanced and the relative expression of SDF1 was unchanged in comparison with MSC from donors. MSC from patients with leukemia were characterized by enhanced relative expression of PDGFRA and PDGFRB, and reduced expression of SOX9. Changes functions of the stromal microenvironment in patients with hemoblastoses attested to the role of stromal cells in the maintenance and spread of tumor cells.

[Successful use of long-term follow-up in patients with chronic myeloid leukemia with a deep molecular response at reduced doses of 2nd generation tyrosine kinase inhibitors: clinical cases and literature review].

Therapy with tyrosine kinase inhibitors (TKI) allows to achieve a deep molecular response in 6070% of patients with chronic myeloid leukemia (CML). According to the current guidelines CML patients receive a long-term treatment with TKI in standard dose. The frequently observed adverse effects (AE) of TKI therapy are mostly dose-dependent. A new treatment approach with TKI use in reduced dose is desirable for the CML patients with existing AE or with a high risk of AE occurrence. We report the two cases of successful long-term treatment of CML patients with reduced doses of second generation TKIs. The aim of the TKI dose reduction was to reduce the clinical manifestations of drug toxicities and to prevent the AE.

Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors.

We analyzed changes in multipotent mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of tyrosine kinase inhibitors. Withdrawal syndrome was significantly more common in patients who have been taking tyrosine kinase inhibitors for a longer time and in patients of older age and with lower body weight. In patients with withdrawal syndrome, the total production of mesenchymal stromal cells and expression of FGFR2 and MMP2 genes were significantly lower; loss of deep molecular response was also less frequent in this group of patients. At the same time, the expression of genes important for the maintenance of stem cells (SOX9, PDGFRa, and LIF) was significantly lower in the mesenchymal stromal cells of patients with withdrawal syndrome and loss of deep molecular response. We observed a clear-cut relationship between the development of withdrawal syndrome and the loss of deep molecular response. The decrease in the expression of FGFR2 and MMP2 genes in the mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of treatment can be a predictor of withdrawal syndrome, while simultaneous decrease in the expression of SOX9, PDGFRa, and LIF in these cells attests to undesirability of therapy discontinuation at the moment.

Cone beam computed tomography study on the relation between mental foramen and roots of mandibular teeth, presence of anterior loop and satellite foramina.

PURPOSE: To investigate the position of the mental foramen based on its relation with the roots of the mandibular teeth and quantify the prevalence of anterior loop and satellite foramina in the mandible in cone beam computed tomography (CBCT) scans. METHODS: The sample consisted of 400 CBCT scans of males (n=190) and females (n=210) from Moscow, Russia. Using the system proposed by Tebo and Telford (1950), the position of the mental foramen was classified into: I) mesial to the mandibular first premolar; II) at the apex of the mandibular first premolar; III) between the roots of the mandibular first and second premolars; IV) at the apex of the mandibular second premolar; V) between the roots of the mandibular second premolar and first molar; and VI) at the apex of the roots of the mandibular first molar. Additionally, the images were assessed to investigate the prevalence of the anterior loop of the mandibular canal and the presence of satellite foramina. RESULTS: Mental foramen position class III was the most prevalent (61%) followed by class IV (27%), II (8%), I, V and VI (together <4%). Statistically significant differences were not detected between males and females (P<0.05). In Russian males and females, the anterior loop of the mandibular canal was found in 15.78% and 3%, respectively; while satellite foramina were found in 31.58% and 19.62%, respectively. CONCLUSION: The spatial position of the mental foramen and the morphological alterations of the mandibular canal and adjacent foramina must be known prior to surgical interventions in the mandible.

[The long-term results of teeth restoration with composite resin materials: a systematic literature review]. / Otdalennye rezul'taty restavratsii zubov kompozitnymi materialami svetovogo otverzhdeniia: obzor literatury.

AIM: To evaluate by means of a systematic review the survival rate of composite resin restorations in the long-term period and the main factors, affecting the quality of restorations. MATERIAL AND METHODS: An electronic search was performed in eLIBRARY.RU, PubMed/MEDLINE and Scopus. Restriction period was 2007-2017 years. The eligibility criteria included randomized controlled trials, controlled clinical trials and prospective and retrospective cohort studies with at least 3 years of follow-up. RESULTS: The initial search resulted in 328 articles after an initial assessment and careful reading, 17 studies were included in this review. The overall survival rate of composite restorations was 90.7% after 3 years, 89.5% after 5 years, 89.3% after 7 years and 75.6% after 10 years. The highest loss rate was for class II restorations at molars. However there was not enough information about class III and IV restorations and direct veneers. According to majority of publications, type of composite resin material and adhesive system do not affect the survival rate of restorations. The main risk factors of failure are smoking, beverages consumption, bruxism, xerostomia and low level of caries resistance. CONCLUSION: The results of this review suggest that composite resin restorations can demonstrate clinically acceptable results in the long-term period. In case of compliance with treatment protocol the longevity of composite resin restoration is more than 15 years.

[Caries experience and elementary composition of mixed saliva in adult patients with dental fluorosis]. / Intensivnost' kariesa i élementnyi sostav smeshannoi sliuny u vzroslykh patsientov s fliuorozom zubov.

AIM: Caries experience assessment in adult patients with dental fluorosis living in endemic area and in the region with normal fluoride concentration in drinking water; assessment of correlation between DMFT index and elementary composition of mixed saliva in adult patients with dental fluorosis. MATERIAL AND METHODS: Two groups of patients took part in the clinical study. Group 1 involved 33 persons with dental fluorosis living in endemic area. In group 2 there were 31 persons with dental fluorosis living in region with normal fluoride concentration in drinking water. DMFT index was calculated. Enamel resistance to acids and remineralizing activity of saliva were tested. Electron probe X-ray microanalysis (EPXMA) was used to detect elementary composition of mixed saliva. RESULTS: The mean DMFT value was 3.97±0.31 in group 1 and 4.65±0.41 in group 2, which was 15% higher. In both groups high enamel resistance to acids was observed, but remineralizing activity of saliva was significantly better in group 1. The mean fluoride concentration in mixed saliva was 42% higher in group 1 comparing to group 2 (0.108±0.003 mass%, and 0.063±0.0002 mass%, respectively). CONCLUSION: Adult patients with dental fluorosis living in endemic area are more caries resistant comparing to those living in region with normal fluoride concentration in drinking water. It's associated with elevated fluoride concentration in mixed saliva due to permanent fluoride consumption with drinking water.

[Oral health in patients with systemic sclerosis]. / Stomatologicheskii status patsientov s sistemnoi sklerodermiei.

The aim of this study was to conduct literature review about oral manifestations of scleroderma. Systemic sclerosis is a multisystem autoimmune disorder characterized by widespread fibrosis, vascular alterations and inflammation. Systemic sclerosis mainly affects people in age from 30 to 50 years, but the onset of disease can occur in any age. The disturbance of microcirculation with the activation and proliferation of endothelium and smooth muscle cells plays an important role in pathogenesis of sclerodrma. These changes lead to sclerosis and fibrosis of various part in human body. Orofacial manifestations of scleroderma include: reduced mouth opening, widening of periodontal ligament, teleangiectasia, bone lesions. Systemic scleroderma is often accompanied by Sjogren's syndrome. Oral manifestations of Sjogren's syndrome are recurrent parotitis, angular cheilitis, xerostomia and multiple caries. Sjogren's syndrome leads to negative impact on patients health and mental status. Orofacial manifestations of systemic sclerosis are still poorly known, that is why more researches should be made to improve dental treatment of patients with systemic sclerosis.

[Efficiency of chronic apical periodontitis treatment with use of Granulotec endodontic sealer]. / Éffektivnost' lecheniia khronicheskogo periodontita s ispol'zovaniem materiala Granulotec dlia postoiannoi obturatsii kornevogo kanala.

AIM: Efficiency assessment of Granulotec (PD) endodontic sealer for root canal permanent obturation in patients with apical granuloma basing on clinical and radiological data. MATERIAL AND METHODS: Endodontic treatment of 35 teeth with apical granuloma was performed in 22 patients with root canal obturation by means of lateral condensation with Granulotec sealer. Bone remodeling in periapical area has been estimated in 1, 3, 6 and 8 months with PAI index. RESULTS: Endodontic post-operative pain has been observed in 5 (14.3%) cases of 35, pain duration varied 1 to 5 days, NSAIDs use hasn't been required. During observation period 2 teeth have been excluded from the test group (one case of periapical abscess with sinus tract and one case periapical abscess without sinus tract). In the end of observation period complete bone remodeling was observed in 30 cases, the periapical lesion size significant reduction was achieved in 2 cases, periapical lesion stabilization - in 1 case. The overall success rate was 91.4%. The mean PAI value decreased from 4.2±0.2 to 1.4±0.2. CONCLUSION: The Granulotec (PD) use for one visit chronic apical periodontitis treatment allows achieving positive results with low complications risk.

[Comparison of interdental oral hygiene aids efficiency in patients with healthy periodontium: a split-mouth study]. / Sravnitel'naia otsenka éffektivnosti sredstv interdental'noi gigieny rta u patsientov so zdorovym parodontom: issledovanie split-mouth.

AIM: Comparison of different interdental aids efficiency in patients with healthy periodontium. METHODS: A non-randomized controlled split-mouth study was carried out in 25 young adults with healthy periodontium. The mouth was divided into 4 quadrants. All the participants used manual toothbrush. Additional hygienic aids included SPS prime (Curaprox) interdental in quadrant 1 brushes, dental floss (Curaprox) in quadrant 2, unituft toothbrush (Curaprox) in quadrant 3, no interdental aids were used in quadrant 4. The oral hygiene efficiency was assessed after 4 weeks with Silness-Loe Plaque Index (PI) and Rustogi et al. Modified Navy Plaque Index (RMNPI). RESULTS: After 4 weeks the mean value of PI decreased from 1.2±0.27 to 0.7±0.28, the mean value of RMNPI decreased from 0.7±0.11 to 0.5±0.16. At the primary examination, there was no statistically significant difference of PI and RMNPI values between the quadrants. After 4 weeks, ANOVA test demonstrated significant difference between the quadrants. The minimal PI and RMNPI values were determined in quadrant 1 (0.4±0.16 and 0.3±0.11, respectively). The maximal PI and RMNPI values were determined in quadrant 4 (1.0±0.21 and 0.6±0.14, respectively). There was no significant difference between quadrants 2 and 3. CONCLUSION: In limitations of this study, the maximal oral hygiene efficiency was achieved with use of manual toothbrush combined with interdental brush.

[Comparative effectiveness of therapeutic toothpastes with fluoride and hydroxyapatite]. / Sravnitel'naia otsenka éffektivnosti lechebno-profilakticheskikh zubnykh past, soderzhashchikh ftorid i gidroksiapatit.

The purpose of the study was to assess the impact of toothpastes containing hydroxyapatite and fluoride on enamel caries resistance and remineralization rate. Study groups comprised 160 patients divided in 2 groups of 80 patients: 40 - at the age of 15-17 and 40 at the age of 18-25 who have been using toothpastes with hydroxyapatite and fluoride during 1 year. The plaque determination was carried out with the use of OHI-S and Turesky indexes. Litmus test pieces were used to determine oral fluid pH. The clinical determination of enamel remineralization rate, dynamics of acid resistance of enamel were carried out. Oral hygiene at baseline examination was poor in both groups. After oral hygiene training, there was a tendency towards indexes decrease more pronounced in the 18-25 age group regardless of the composition of the toothpastes used. Mean baseline oral fluid pH in the observation group was 6.5±0.4, in the comparison group - 6.8±0.4. By the end of the trial there was a tendency towards the increase of the oral fluid pH, which were 7.3±0.3 and 7.7±0.3, respectively. The enamel acid resistance of the patients of the observation group was significantly higher (p>0.05) compared with the group of patients using fluoride toothpaste, as well as the proportion of patients in whom the enamel recovery occurred within 24 hours (47.5% vs. 22.5%, respectively).

[Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy]. / Rezul'taty nabliudeniia bol'nykh khronicheskim mieloleikozom s glubokim molekuliarnym otvetom bez terapii ingibitorami tirozinkinaz.

AIM: To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. SUBJECTS AND METHODS: The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year's duration were adverse events, pregnancy, and patients' decision. Information was collected retrospectively and prospectively in 2008-2016. RESULTS: The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. CONCLUSION: Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.

[Assessment of antibacterial efficacy of ozone therapy in treatment of caries at the white spot stage]. / Antibakterial'naia éffektivnost' ozonoterapii pri lechenii kariesa v stadii belogo piatna.

Effect on cariogenic flora is the key toremineralizing therapy efficacy in treatment of initial caries (at the white spot stage). Ozone in dentistry is used as a highly effective antibacterial agent. Treatment of white spot lesions with the ozone-air mixture leads to significant increase of efficacy in non-invasive treatment of initial caries. OBJECTIVE: clinical and microbiological assessment of antibacterial efficacy of ozone therapy in treatment of caries at the white spot stage. MATERIAL AND METHODS: The trial recruited 86 patients for non-invasive treatment of caries at the white spot stage which included the complex of professional oral hygiene, medicamental treatment of white spot lesions with hydrogen peroxide 3% and chlorhexidinedigluconate 0,2%, treatment with the ozone-air mixture and application of hydroxyapatite Са2+. Material for microbiological study was received before the treatment, after the complex of professional oral hygiene and medicamental treatment of white spot lesions conducted as well as after the treatment with the ozone-air mixture. RESULTS: Before the treatment up to 16 kinds of microorganisms on the surface of white spot lesion were detected with the following shares: S. mutans (19.9%), S. salivarius (15.1%), S. epidermidis (8.7%), S. mitis (6.5%), Lactobacillus (6.5%) and different kinds of staphylococci (10.8%). After the complex of professional oral hygiene and medicamental treatment conducted decrease in number of cariogenic microorganisms was indicated as follows: S. mutans - from 1·105 to 1·104, S. salivarius - from 1·107 to 1·106, S. epidermidis - from 1·105 to 1·104, S. mitis - from 1·104 to 1·103, Lactobacillus - from 1·104 tо 1·103. After the treatment of tooth enamel with the ozone-air mixture increase in microorganisms was not observed. The efficacy of ozone on cariogenic microorganisms exceeds significantly the efficacy of 3% hydrogen peroxide and 0,2% chlorhexidinedigluconate. CONCLUSION: It is strongly advisable to include ozone in protocol of non-invasive treatment of initial dental caries.

[A rare case of myeloproliferative disease with t(8;13)(p11;q12) associated with eosinophilia and lymphadenopathy]. / Redkii sluchai mieloproliferativnogo zabolevaniya s t(8;13)(p11;q12), protekayushchego s eozinofiliei i limfadenopatiei.

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

[Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera]. / Effektivnost' interferonoterapii u bol'nykh essentsial'noi trombotsitemiei i istinnoi politsitemiei.

AIM: To evaluate the efficiency of interferon (IFN) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). SUBJECTS AND METHODS: A total of 61 patients (41 with ET and 20 with PV) were examined. Prior to study enrolment, 44 (72%) patients with ET or PV received one or other therapy (aspirin was not taken into account). The mean Jak2V617F mutant allele at baseline was 23% (6-54%) in the patients with ET and 40% (11-88%) in those with PV. The median time from diagnosis to enrollment was 49 months. RESULTS: The paper presents the clinical and molecular findings of long-term INF-α therapy in patients with ET or PV. The median follow-up was 52 months. Recombinant IFN-α2 showed its ability to induce complete hematologic remission (ET (76%), PV (70%)) and a complete molecular response. 22 (69%) out of 32 patients were noted to have a smaller number of cells with the Jak2V617F mutation. In the patients with PV and in those with ET, the relative reduction in the proportion of cells with the Jak2V617F mutant gene averaged 85% and 56% of the baseline values, respectively. There was a reduction in the proportion of cells expressing the Jak2V617F mutation in both the ET (from 12 to 2.2%; p=0.001) and PV (from 32.7% to 3.2%) groups (р=0.001). Ten (31%) patients achieved a deep molecular remission (≤2% Jak2V617F allele); among them, 5 patients were not found to have Jak2V617F mutation. The obtained molecular response remained in 7 of the 10 patients untreated for 11 to 86 months. The long-term treatment with IFN-α led to normalization of the morphological pattern of bone marrow in 5 of the 7 PV or ET patients. CONCLUSION: Significant molecular remissions achieved by therapy with recombinant interferon-α2 confirm the appropriateness of this treatment option in in the majority of patients with ET or PV.

[FIP1L1-PDGFRА-positive myeloproliferative disease with eosinophilia: A rare case with multiple organ dysfunction and a response to tyrosine kinase inhibitor therapy].

The described case of FIP1L1-PDGFRА-positive myeloproliferative disease is characterized by an atypical aggressive course to develop severe specific complications as injuries to the brain, heart, lung, and intestine. Pathogenetic therapy with imatinib could stabilize a patient's state, but failed to produce a complete hematological response. Switching from imatinib to dasatinib could produce sustained clinical, hematological, and molecular remissions.

[Synchronous and metachronous myeloid and lymphoid tumors].

AIM: To determine the clinical features of multiple primary tumors (MPT) in patients with hemoblastoses, to develop treatment policy for synchronous and metachronous tumors, and to determine the impact of chemotherapy for one disease on the course and prognosis of another one. SUBJECTS AND METHODS: The investigation included 20 patients with multiple primary synchronous and metachronous myeloid and lymphoid tumors, who had been followed up at the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation. The distribution of patients by nosological entities was as follows: 17 (85%) patients with myeloproliferative diseases (MPDs) concurrent with lymphoproliferative diseases (LPDs) and 3 (15%) with two types of MPD. A special group comprised 3 patients who successively developed 3 malignant diseases: cancer/B-cell chronic lymphocytic leukemia (B-CLL)/Ph-positive chronic myeloid leukemia (Ph+CML); cancer/polycythemia vera (PCV)/B-CLL; cancer/essential thrombocythemia (ETC)/multiple myeloma (MM). RESULTS: The Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, followed up 20 patients with synchronous and metachronous tumors in 1996 to 2013. The patients' age was 42 to 82 years (64 years). The female/male ratio was 1:1.2. Metachronous tumors were 1.5-fold higher than synchronous ones. The time to detection of secondary hemoblastosis averaged 3.3 years; the longest interval was 14 years; the mean coexistence of 2 tumors was 4.8 years (1-11 years). The total length of the follow-up was 8 years (1-19 years). Among them, there were 17 (85%) patients with 2 chronic hematologic tumors with a myeloid or lymphoid phenotype; 3 (15%) of the 20 patients had 3 malignant diseases (cancer/ B-CLL)/Ph+CML, cancer/PCV/B-CLL, cancer/ETC/MM. In the group of 17 patients, 13 (76%) were diagnosed as having Ph-negative MPDs (PCV in 4 patients, primary myelofibrosis in 4, ETC in 4, undifferentiated MPD in1) and 4 (24%) patients had Ph+CML. This patient group was found to have the following LPDs: CLL in 5 (30%), hairy cell leukemia in 1 (5%), paraproteinemic hemoblastoses in 11 (65%). MPD preceded LPD in 8 (47%) patients; the development interval between two tumors averaged 6 years (1 to 14 years). LPD preceded MPD in 3 (18%) patients; the interval averaged 5 years (2 to 17 years). MPD and LPD appeared synchronously in 6 (35%) patients. CONCLUSION: The fact that 2 malignancies or more may occur in one patient determines the need for a careful follow-up of patients with blood system diseases. The activity of one hematologic disease or another is a leading criterion for choosing a therapeutic tactic.

[Incidence of chronic myeloid leukemia in 6 regions of Russia according to the data of the 2009-2012 population-based study].

AIM: To assess the main epidemiological characteristics of chronic myeloid leukemia (CML) in the Russian Federation. SUBJECTS AND METHODS: A planned epidemiological prospective study was conducted in 2009-2012 in 6 Russian regions with the total number of 10.1 million inhabitants, which notified all new CML cases. RESULTS: The unstandardized (unnormalized, baseline) recorded incidence of CML in the examined regions was 0.58 per 100,000 annually. Its standardized (normalized) incidence was 0.70 for the WHO standard population and 0.72 for the European standard population. The regional variations in the incidence were 0.44 to 0.69. The structural analysis of the incidence in the age strata indicated that the overall morbidity was less due to the decreased rate of registration in old age groups. The morbidity rates in patients aged less than 60 years were nearly similar to the European rates; those in patients aged over 70 years were almost 10 times lower. The lower rate of detection and screening diagnosis of CML in pensioners in primary health care is discussed. CONCLUSION: The data obtained in this study may serve as the starting point for monitoring the CML epidemiological situation.

[Therapeutic strategy for chronic myeloid leukemia: possibilities and prospects].

Over the past decade the clinical introduction of agents that directionally blocks the activity of BCR-ABL tumor tyrosine kinase (TK) has changed the prognosis of chronic myeloid leukemia. A significant malignant Ph'-positive clone inhibition and durable remissions have made it possible to increase overall and relapse-free survival. Due to their higher life expectancy, the number of patients is on the increase and their quality of life and working capacity remain good. According to the All-Russian Register of Chronic Myeloid Leukemia, there were more than 6500 cases in the Russian Federation in 2012. Of them, 93.1% were diagnosed with the chronic phase of the disease, 6.4 and 0.4% with its accelerated phase and blast crisis, respectively. Among the BCR-ABL TK inhibitors (TKI) registered in the Russian Federation and recommended for the treatment of chronic myeloid leukemia, there are 3 medications: imatinib, nilotinib, and dasatinib. The efficiency and safety of TKI therapy have been well studied. The most important principle of treatment is to permanently affect the Ph'-positive tumor cell clone by the long-term daily use of TKls. Regular cytogenetic and molecular genetic monitoring allows adequate estimation of the leukemic clone volume and it is essential in evaluating the therapeutic effectiveness. To choose a TKI for each specific patient with regard for its best tolerability and maximum efficiency permits individualized treatment. The prospect of therapy discontinuation can be discussed only in individual patients with a durable and stable complete molecular response and only within clinical trials.

[Parodontocid efficiency in complex treatment and prevention of gingivitis].

Antiplaque/antigingivitis effect of an alcohol-free mouthrinse Parodontocid were evaluated by randomized parallel group clinical trial. Sixty patients with gingivitis were clinically examined to determine PHP, RMNPI and PMA indexes. After professional dental prophylaxis, subjects were randomly assigned in two groups to 10 days oral hygiene program. Group 1 patients used only toothbrush and prophylactic toothpaste while in group 2 persons used Parodontocid in conjunction with normal brushing and flossing.Parodontocid significantly reduced plaque and gingivitis compared to negative control.