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BACKGROUND Quality of life (QoL) assessment before and after surgical treatment in patients with primary hyperparathyroidism (PHTP) may be useful for comprehensive evaluation of the treatment effect, as well as for monitoring of the patient' condition after surgery, including in real clinical practice. AIM The aim of the study was to validate and test the Russian version of the PHPQoL questionnaire for assessment of the quality of life (QoL) in patients with primary hyperparathyroidism (PHPT) for further application in clinical practice and research in Russia. MATERIALS AND METHODS The linguistic and cultural adaptation of the PHPQoL questionnaire was carried out in accordance with international guidelines. Psychometric properties of the tool, namely, its reliability, validity and sensitivity were tested in the focus group of patients with PHPTResults: In the whole, 65 patients with PHPT were involved into the study (mean age - 52.3 ± 10.5 years, 97% - -women): 67.7% patients were symptomatic, 35.4% patients had moderate or severe hypercalcemia. All the patients filled out the Russian version of PHPQoL before parathyroidectomy. One third of patients filled out the Russian version of PHPQoL twice - before surgery and 3 months after surgery. Satisfactory external and content validity of the Russian version of PHPQoL was demonstrated. Its stable structure confirmed satisfactory construct validity of the questionnaire. The ability of the tool to determine differences in severity of symptoms/problems due to PHPT before and after treatment was revealed. The positive effect of the surgery on QoL in PHPT patients was shown. CONCLUSION The results obtained during the study confirm that the Russian version of PHPQoL is a reliable, valid and sensitive tool. Feasibility and applicability of its use in research and clinical practice in Russian endocrinology settings has been demonstrated.

The aim of the present study was to test a hypothesis that baseline systemic vascular resistance index (SVRI) assessed by method of transpulmonary thermodilution predicts perioperative requirement for vasoactive drugs. The primary outcomes were: (1) peak vasoactive-inotropic score (VIS) and (2) peak dose of hypotensive drugs at any stage of surgery. The main exposure variable was baseline SVRI. Hemodynamics were retrospectively assessed by transpulmonary thermodilution in 50 adults who had undergone posterior retroperitoneal surgery for pheochromocytoma. Univariate linear regression analysis showed predictive value of SVRI on VIS [regression coefficient, 95% CI; 0.024 (0.005, 0.4), p=0.015]. Other significant factors were the history of peak diastolic pressure, baseline MAP, baseline betablocker therapy, and history of coronary artery disease (CAD). After adjustment of SVRI for the history of CAD, its prognostic value became non-significant [0.018 (0.008, 0.03), p=0.063 and 29.6 (19, 40.2), p=0.007 for SVRI and history of CAD, respectively]. Requirements of vasodilators were predicted by baseline adrenergic activity [0.37 (0.005, 0.74), p=0.047]. In conclusion, baseline SVRI is associated with perioperative requirement of vasopressor drugs, but history of CAD is a stronger prognostic factor for vasopressor support. Perioperative requirement in vasodilators is associated with baseline adrenergic activity.

Data in Brief 34, 106651 (2021). doi:10.1016/j.dib.2020.106651, Published by Elsevier, Amsterdam [u.a.]

Background.Tumor tissue in classical Hodgkin Lymphoma (cHL) contains 1-10% malignant Hodgkin/Reed-Sternberg cells and a significant number of immune cells in the tumor microenvironment that are characterized by expression of inhibitory molecules (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT). Despite overall effectiveness of anti-PD-1 treatment many patients still have relapsed or refractory (r/r) disease, therefore the search for predictive/prognostic biomarkers in patients on immunotherapy is highly demanded. Materials and methods.The study included 39 primary tumor specimens from patients with r/r cHL obtained before starting the treatment with nivolumab (primary biopsies). Specimens from 11 patients were studied before and after treatment (sequential biopsies). Treatment response was evaluated by PET-CT according to LYRIC criteria. Immunohistochemical staining for CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT was performed with an automated staining system (Bond III; Leica Biosystems). The slides were scanned with Aperio ScanScope XT (AperioTechnologies Inc.) and were analyzed with ImageScope Analysis software (Aperio Technologies) и Qupath (https://qupath.github.io). We explored progression-free survival (PFS) depending on the proportion of cells positive for CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT in the tumor microenvironment and analyzed the changes of these parameters between primary and sequential biopsies after treatment with nivolumab. Statistical analysis was performed using SPSS software (v.23). Data on sequential biopsies were analyzed with the Wilcoxon signed-rank test. PFS was calculated with the Kaplan-Meier method. The significance level was p ≤ 0.05. Results.A significant correlation was found in primary biopsies group between the value of CD163 and CTLA-4 (correlation coefficient -0,62, p < 0.05). There was no significant association between PFS and proportion of cells positive for CD68, PD-1, TIM-3, CTLA-4, TIGIT, LAG-3 in primary biopsies group. ROC analysis allowed to establish a 9% cut-off value of CD163 expression, dividing these patients into subgroups of CD163high and CD163low. In the CD163low group, the two-year PFS was 19,1% (95% CI 6%-37,7%) with a median PFS of 8,8 months (95% CI 5,7-12) and in the CD163high group - 53,8% (95% CI 28,4%-73,7%) with a median of 24,8 months (95% CI 18,8 - 39,2). In sequential biopsies, a statistically significant increase in numbers of PD-1+ and TIGIT+ T-cells and depletion of CD68+ and CD163+ cells was observed compared to corresponding cell counts in primary biopsies (median PD-1 - 3% vs 10%; median TIGIT - 10% vs 14%; median CD68 - 10% vs 7%; median CD163- 8% vs 3,5%; р Conclusion.A comprehensive analysis of expression of CD68, CD163, LAG-3, TIGIT, CTLA4, TIM-3, PD-1 was performed in patients with r/r cHL before and after treatment with nivolumab. Significant association was found between the expression of CD163 and CTLA4. The results of the study indicate inferior PFS among patients with low expression ( This study was supported by BMS research grant CA209-8EG Disclosures Ionova: Takeda:Other: principal investigator of the observational studies sponsored by Takeda;BMS:Other: principal investigator of the observational studies sponsored by BMS.

Background The criteria of molecular relapse in different treatment-free remission (TFR) trials in patients (pts) with chronic myeloid leukemia (CML) varied. In the early trials molecular relapse was defined as loss of deep molecular response (DMR) including MR4 loss. In recent ELN guideline (Hochhaus et al, 2020) major molecular response (MMR) loss was a criterion of molecular relapse. We consider it reasonable to evaluate the role of MR4 loss in connection with MMR loss and time of treatment-free observation and to describe the pattern of minimal residual disease (MRD) in this context. Aim To evaluate the role of MR4 loss on further MMR loss in CML pts during early and late period after TKI cessation and to describe the pattern of MRD during TFR. Patients and methods In total 98 CML pts with chronic phase who had received therapy by any TKI ≥3 years (yrs) with sustained DMR (at least MR4 or BCR-ABL ≤0.01% by international scale (IS)) during ≥2 yrs) were enrolled into the prospective TFR study RU-SKI. The BCR-ABL level (IS) was evaluated by RQ-PCR monthly during the first 6 months (mo) after TKI cessation, every 2 mo from 6 to 12 mo and every 3 mo thereafter. MR4 loss was considered if BCR-ABL was >0,01% and 0,1%). Molecular relapse free survival (MRFS) was evaluated by Kaplan-Meier method, log-rank test was used for comparison. Results Меdian (Me) time after TKI discontinuation was 40 mo (range 28-57). MMR loss and MR4 loss was observed in 48(49%) and 38(39%) pts respectively. In 42(87%) pts MMR loss was observed within first 6 mo after treatment cessation. MRFS at 36 mo was 51% (95% CI 41 - 61%). No MMR loss occurred in 10(26%) pts with MR4 loss while 28(74%) pts with MR4 loss subsequently lost MMR. The MRFS after the first documented MR4 loss was 29% (95% CI 15 - 44%) and 24% (95% CI 10,5 - 38%) at 12 and 24 mo respectively. MRFS at 24 mo was significantly higher in pts with late MR4 loss (>3 mo) than in pts with early MR4 loss ( The pattern of MRD in 50 pts who continued a treatment-free observation after TKI cessation was represented by 3 main variants: 1) stable undetected MRD in 17(34%) pts; 2) transient short-term or long-term fluctuations without MR4 loss in 23(46%) pts; 3) fluctuations with transient MR4 loss but without MMR loss in 10(20%) pts (figure 2). Interestingly, 8 of 10 pts with MR4 fluctuations subsequently achieved MRD-negative status. Conclusion We confirmed that MR4 loss after TKI cessation in most cases (74%) preceded the molecular relapse which was considered as MMR loss. However, the MRFS was significantly higher in pts with late MR4 loss than in those with early MR4 loss during the first 3 mo of TKI cessation and comparable with MRFS in the whole pts cohort. We found that only 34% pts who maintained a molecular remission had stable undetected MRD while 66% of pts had fluctuations of MRD during TFR. About a quarter of pts (26%) with MR4 loss could remain in TFR and achieve the MRD-negative status. We support the importance of regular MRD monitoring both in early and late terms during TFR observation to benefit for the safety of the pts. Disclosures Chelysheva: Novartis: Other: performed lectures; Fusion Pharma: Consultancy. Shukhov:Novartis: Consultancy, Other: performed lectures; Pfizer: Consultancy, Other: performed lectures. Ionova:BMS: Other: principal investigator of the observational studies sponsored by BMS; Takeda: Other: principal investigator of the observational studies sponsored by Takeda. Turkina:Pfizer: Honoraria; Novartis Pharma: Honoraria; BMS: Honoraria.

Background Health related quality of life (HRQoL) of patients with hematological malignancies (HMs) is greatly affected by the disease and the treatment and this has not been captured in a systematic manner in routine clinical practice. A systematic review of the HRQoL issues and instruments used in HM showed gaps between what is important to patients and what is being measured. The aims of this study were to develop and validate an instrument for measuring the impact of HMs and their treatment on patients' HRQoL and symptoms in daily clinical practice. Methods A multicentre Ethics approval was obtained from the National Research Ethics Service (NRES) of South West Bristols, UK. Adult patients with HM as per 2016 Revised WHO classification, capable of reading English and able to give written informed consent, were recruited from inpatient/outpatient clinics of seven secondary care hospitals in England and Wales for all phases of the study (Table 1). The qualitative study employed semi-structured face-to-face interviews. The generated items were then discussed in data definition panel meeting for inclusion in the prototype version of the new instrument. The content validation was followed by item reduction phase where number of items were reduced to more confined set of items. The version of HM-PRO developed after exploratory factory analysis and confirmatory factor analysis was used to perform Rasch modeling. In next step for demonstrating validity of the HM-PRO, construct and convergent/divergent validity was studied. The score banding was developed and MCID was established. Results Face-to-face interviews were performed in 129 patients. The content analysis of the transcribed interviews resulted in a comprehensive item pool. The generated items included in the prototype HM-PRO, were 34 items for impact on HRQoL category (Part A) and 23 items representing disease signs and symptoms (Part B). The version after exploratory and confirmatory factor analysis was used to perform Rasch modeling in 182 patients resulting in 24 items in Part A and 18 items in Part B. The reliability testing (n=150) showed strong stability of measurement with Cronbach's alpha estimates of the HM-PRO for both assessment points (t1 and t2) above 0.9 for Part A, and above 0.8 for Part B. The intraclass correlation coefficient (ICC) for four domains of Part A was 0.85 - 0.91 and >0.8 for the overall scores of Part A and Part B, for all ten diagnoses, confirming strong reliability of the HM-PRO. Construct and convergent/divergent validity were studied in 905 cases. The HM-PRO scores correlated with scores of EORTC QLQ-C30 and FACT-G, both at the scale and at individual item levels. The univariate regression analysis confirmed a strong relationship between the HM-PRO and the other two measures. For the majority of regression models, the HM-PRO domains and individual items explained more than 50% of the variance in domain and item scores of EORTC QLQ-C30 and FACT-G, confirming the construct validity. The responsiveness testing (n=299) showed that HM-PRO is responsive to small but clinically important change in patients' HRQoL. The score banding was developed for the HM-PRO for its interpretability in to day-to-day clinical practice. The MCID for Part A based on standard error of mean was 6.2 and for PART B 5.9 points. It therefore was prudent, for practical reasons, to propose MCID of '6' for the HM-PRO. Conclusion This study provides evidence of the value of HM-PRO through content validity, reliability, construct validity, responsiveness and interpretability. The current research has developed and validated the English version of the HM-PRO. Further studies are being carried out to validate the instrument in several global languages for cross-cultural adaptation. Furthermore, the Acute Leukaemia Advocates Network (ALAN) is using the HM-PRO in a multi-country survey including five European (French, German, Italian, Portuguese, Spanish) and five non-European countries (Chinese, Hebrew, Korean, Japanese, Russian) to generate data in order to understand the impact of the disease and treatment on patients with different types of leukaemia. The data collected from this survey will be used to further validate the HM-PRO specifically in patients with leukaemia and potentially improve management of patients and their treatment. The HM-PRO has good potential to be widely used in daily clinical practice as well as in hemato-oncology clinical trials. Disclosures Kell: Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fielding:Incyte: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Collins:Gilead: Consultancy, Honoraria. Salek:Pfizer: Honoraria, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy, Honoraria; Merck: Consultancy.

Background It is reasonable to incorporate quality of life (QoL) assessment into the comprehensive evaluation of treatment outcomes in chronic myeloid leukemia (CML) patients (pts) with deep molecular response (DMR) who enter the treatment-free remission (TFR) phase and stop therapy by tyrosine kinase inhibitors (TKIs). QoL assessment was included into the design of Russian prospective multicenter trial RU-SKI along with the clinical outcomes evaluation. Aim To study QoL in chronic phase (CP) CML pts with DMR before stopping TKI treatment and during TFR observation. Materials and methods The study has been conducted within the clinical approbation supported by the Ministry of Health of RF. The CML CP pts with therapy by any TKI ≥ 3 years (yrs) and stable DMR (BCR-ABL ≤0.01% IS) during ≥2 yrs were enrolled. Pts who met these criteria and had previous resistance to any TKI were also eligible. TKIs were resumed in case of major molecular response loss (MMR, BCR-ABL>0,1%). The QoL questionnaires RAND SF-36 and EORTC QLQ C30 were filled out by the pts before stopping TKI treatment and at 1, 3, 6 and 12 months (mo) after treatment discontinuation. The comparison group consisted of healthy persons matched by age and gender to CML CP pts (n=97). The Mann-Whitney test, paired Wilcoxon test and Generalized Estimation Equations (GEE) with adjustment to age, gender, the risk group according to Sokal score and duration of TKI treatment were used for the statistical analysis. Results QoL assessment was performed in all 99 CML CP pts who were enrolled into the trial during a period from Aug 2015 till Dec 2017. The TKIs before treatment cessation were as follows: imatinib and second-generation (2G) TKIs were used in 69(70%) and 30(30%) pts accordingly. 2G TKIs were used in 9(30%) and in 21(70%) pts as 1st and 2nd line accordingly. Mean age was 47±14.5 yrs, 48.5% were males, 12.1% had high Sokal risk score. The physical functioning of CML pts before stopping TKI treatment compared to the healthy controls was significantly worse (p0.05). Conclusion The QoL in CML CP pts with DMR on TKI treatment is slightly worse and physical functioning is significantly lower as compared to healthy controls. The positive changes of the role functioning along with TKI treatment-related symptoms decrease were revealed in pts who maintained stable MMR during 12 mo of TFR. No changes in QoL and no new symptoms were found in pts who reinitiated treatment before and after TKIs interruption. The results of QoL assessment may contribute to optimization of the treatment strategies of CML patients with DMR. Disclosures Chelysheva: Fusion Pharma: Other: provided consultations ; Bristol Myers Squibb: Other: provided consultations and performed lectures; Novartis: Other: provided consultations and performed lectures. Shukhov:Bristol Myers Squibb: Other: provided consultations and performed lectures ; Novartis: Other: provided consultations and performed lectures . Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations. Ionova:Takeda: Research Funding; BMS: Research Funding.

The Russian Federation is a country with a high cancer morbidity, which unfortunately has a tendency to increase annually. For example, St. Petersburg, the second largest city in Russia (population 5 million people) has the highest cancer morbidity in Russia, with more than 17,000 new patients per year. 1 In the Novosibirsk region, which covers a large territory of the Russian Federation, cancer morbidity is 333.5 per 100,000 citizens and has an annual increase of 5–6%. The majority of Russian patients with cancer are diagnosed with advanced disease. Palliative treatment for these patients is far from perfect. This can be explained by a number of factors. First, the lack of knowledge of the basic principles of palliation and a deficiency of skilled specialists pose obstacles to creating a structure for palliative care in Russia. Second, there are legislation limitations and problems of drug use regulation. Finally, evaluation of symptom severity and prevalence, its impact on quality of life, and adequacy of treatment, as well as studies of the barriers to effective palliative care and symptom management, are absolutely new in Russia. An extensive search of the current literature has found no citations describing the status of symptom control in cancer patients in Russia. Based on studies that have been done in countries with more health resources, we can expect symptom prevalence and severity to be greater among Russian cancer patients than in such countries as the United States and France. 2

Abstract 2317 Poster Board II-294 High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) offers promising results in the treatment of multiple sclerosis (MS) patients. Reduced intensity conditioning regimens (RIC-AHSCT) is a way to improve the balance between benefits and side effects of this treatment approach. The goal of our research was to study the safety and treatment outcomes of RIC-AHSCT in patients with various types of MS. One hundred thirty six patients with MS: secondary progressive (SP) – 48 patients, primary progressive (PP) – 23, progressive-relapsing (PR) – 5 and relapsing-remitting (RR) – 60, were included in this study (mean age - 33.0, range: 17-54; male/female – 57/79). The conditioning regimen included reduced or modified BEAM. The median EDSS at base-line was 4.0 (range 1.5 – 8.5). The median follow-up duration was 17.2 months (range 6 – 35 months). Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter AHSCT. MRI examinations were performed at baseline, at 6, 12 months, and at the end of follow-up. No transplant-related deaths were observed. Transplantation procedure was well tolerated by the patients with no unpredictable severe adverse events. Among 91 patients included in the efficacy analysis 44 patients (48.5%) experienced clinical stabilization; 46 (50.5%) – improvement, and 1 patient (1%) – progression 6 months post-transplant. Among 31 SPMS patients 16 improved and 15 – stabilized; among 15 PPMS patients 7 improved, 7 – stabilized, and one progressed (PPMS); among 42 RRMS patients 20 improved and 22 – stabilized. In 12 months post-transplant 66% patients improved and 32% – stabilized. One patient (SPMS) progressed after 6 months stabilization. Relapses within the first year post-transplant were registered in 3 patients (2 SPMS; 1 PRMS). No active, new or enlarging lesions on MRI were registered in patients without disease progression. In conclusion, this study provides ample evidence in support of safety and efficacy of reduced intensity conditioning AHSCT in patients with various types of MS. The collection of long-term follow-up data is worthwhile to verify these findings. The rationale of evolution from myeloablative to non-myeloablative transplant regimens should be confirmed by the further studies. Disclosures: No relevant conflicts of interest to declare.

Conventional therapies do not provide satisfactory control of multiple sclerosis (MS) due to their inability to eradicate self-specific T cell clones. Recently, high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) was proposed as a new and promising therapy for MS patients. Taking into account the information about high risk of transplant-related mortality and severe side effects of myeloablative conditioning regimens, the rationale to use non-myeloablative regimens sounds reasonable. The goal of our research was to study the safety and efficacy of mini-AHSCT in MS patients. Fifty three patients with MS (secondary progressive – 16 patients, primary progressive – 12, progressive-relapsing – 3 and relapsing-remitting – 22) were included in this study (mean age - 30.0, range: 17–47; male/female – 23/30). The conditioning regimen included reduced or modified BEAM. Median EDSS at base-line was 4.0 (range 1.5 – 8.0). The median follow-up duration was 7 months (range 6 – 20 months). Neurological and quality of Life (QoL) evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter AHSCT. MRI examinations were performed at baseline, at 6, 12 months, and at the end of follow-up. Transplantation procedure was well tolerated by the patients with no transplant-related deaths. Among 29 patients included in the efficacy analysis 15 patients (52%) experienced clinical stabilization; 14 (48%) – improvement. EDSS improved by 0.5 points in 11 patients, by 1.0 points in 2 patients, by 2.0 points in 1 patient. One patient progressed after 6 months stabilization. No active, new or enlarging lesions were registered in patients without disease progression. Out of 27 patients included in QoL analysis 21 exhibited QoL improvement and 4 – stabilization during the follow-up; QoL worsened in 2 patients. All the patients without disease progression were off therapy throughout the post-transplant period. In conclusion, mini-AHSCT may be considered as a new, safe and effective treatment for MS. The results of mini-AHSCT in MS patients are promising both in terms of clinical and patient-reported outcomes. The collection of long-term follow-up data is worthwhile to verify these findings. The rationale of evolution from myeloablative to non-myeloablative transplant regimens should be confirmed by the further studies.

Conventional therapies do not provide satisfactory control of multiple sclerosis (MS) due to their inability to eradicate self-specific T cell clones. During the last decade high-dose immunosuppressive therapy (HDIT) with autologous haematopoietic stem cell transplantation (AHSCT) has been used with increasing frequency as a therapeutic option for MS patients. We have identified 4 strategies of HDIT+AHSCT depending on the stage in disease process: early, conventional, late, and salvage. In the current study we aimed to study clinical and patient-reported outcomes in MS patients after different strategies of HDIT+AHSCT. One hundred and twenty patients with MS (secondary progressive – 53 patients, primary progressive –21, progressive-relapsing – 9, relapsing-remitting – 37) were included in this study (mean age - 33.0, range: 17–54; male/female – 53/67). Thirty seven patients underwent early transplantation (EDSS 1.0–3.0), 72 patients – conventional transplantation (EDSS 3.5–6.0), 6 patients – late transplantation (EDSS 6.5–7.0), and 5 patients – salvage transplantation (EDSS 7.5–8.5). Median EDSS at baseline was 5.0 (range 1.5 – 8.0). The mean follow-up duration was 18 months (range 6 – 108 months). Neurological and quality of life (QoL) evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter following AHSCT; MRI examinations - at baseline, at 6, 12 months, and at the end of follow-up. Notably, transplantation procedure was well tolerated by the patients with no transplant-related deaths. The efficacy analysis was performed in 79 patients. At 6 months post transplant the following distribution of patients according to clinical response was observed: 42 patients (53%) achieved an objective improvement of neurological symptoms; 37 patients (47%) had disease stabilization. At long-term follow-up clinical response was classified as improvement in 40 patients (50.6%); stabilization in 34 patients (43.1%); progression in 5 patients (1 patient after early transplantation, 3 patients after conventional transplantation, and 1 patient after late transplantation). No active, new or enlarging lesions were registered in patients without disease progression. Furthermore, out of 44 patients included in QoL analysis 39 exhibited improved QoL 6 months post-transplantation. Further QoL improvement was observed at longer follow-up in patients without disease progression. All the patients without disease progression were off therapy throughout the post-transplant period. Thus, AHSCT appears to be an effective treatment for MS both in terms of clinical and patient-reported outcomes. Further studies should be done to establish the best timing for transplantation and to validate high-dose immunosuppressive therapy with ASCT regimens in patients receiving early, conventional, late and salvage transplantation.

During the last decade HDCT+ASCT is more often used as a therapeutic option for MS patients. The major treatment outcomes for MS patients are disease-progressive free period and improvement of patient’s quality of life (QoL). We aimed to study treatment outcomes in MS patients after early, conventional and salvage HDCT+ASCT. Thirty two patients with MS (secondary progressive - 16 patients, primary progressive - 8, progressive-relapsing - 1, relapsing-remitting - 7) from 6 medical centers were included in this study (mean age - 32.0, range: 19–49; male/female - 12/20). Two patients underwent early HDCT +ASCT, 27 patients - conventional HDCT+ASCT and 3 patients - salvage HDCT+ASCT. Median EDSS at base-line was 6.0 (range 2.0 – 8.0). The median follow-up duration was 18 months (range 6 – 78 months). All of the patients had previously undergone conventional treatment. Neurological and QoL evaluation was provided at baseline, at discharge, 3, 6, 9, 12 months, and then every 6 months after HDCT+ASCT. MRI was conducted at baseline, at 6, 12 months, and at the end of follow-up. FACT-BMT and FAMS were used for QoL evaluation. QoL response was evaluated using Integral QoL index. All 27 patients with the follow-up longer than 1 year, included in the analysis, experienced a clinical stabilization or improvement. More than half of them improved: 6 patients showed significant improvement in EDSS (by more than 1.0 point), 4 patients improved by 1.0 point, and 5 patients - by 0.5 points on EDSS. Twelve patients achieved stabilization. Two patients deteriorated to a worse score after 18 months of stabilization; 2 other patients progressed after 12 and 30 months of improvement, respectively. All the patients with clinical stabilization and improvement exhibited negative MRI scans. Out of 21 patients included in the analysis of QoL response 19 exhibited improved QoL 6 months post-transplantation. At one year after HDCT+ASCT 1 patient exhibited excellent QoL response; 3 patients - good QoL response; 7 patients - moderate QoL response and 8 patients - minimal QoL response. At 2.5 years post-transplantation 3 more patients had excellent QoL response. Further QoL improvement was observed at longer follow-up. One of the patients who experienced progression after stabilization had no QoL response; another patient who progressed after stabilization had stable QoL during 6 months post-transplant and significantly worsened at 9 months. In conclusion, clinical response was observed in 100% of MS patients after early, conventional and salvages HDCT+ASCT. The majority of patients with clinical response had a good or moderate QoL response. Further studies should be done to investigate the clinical and patient-reported outcomes of HDCT+ASCT in MS patients to better define treatment success.

HDCT+ASCT is a new and promising therapy for MS patients. Among a number of unclear questions is the terms of conducting HDCT+ASCT. According to our concept there are 3 strategies of HDCT+ASCT depending on the terms of disease process: early, conventional and salvage. Another important consideration is that the major treatment outcomes for MS patients are disease-progressive free period and improvement of patient’s quality of life (QoL). With this in mind, evaluation of both clinical and patient-reported outcomes in MS patients after HDCT+ASCT is worthwhile. We aimed to study the clinical and QoL response in MS patients after early, conventional and salvage HDCT +ASCT. 17 patients with MS (secondary progressive − 8 patients, primary progressive − 6, progressive relapsing − 2, relapsing remitting − 1) were included in the study (mean age − 32.3, SD − 6.6; male/female − 4/13). Fifteen patients underwent conventional HDCT +ASCT; one patient (relapsing-remitting MS) - early HDCT+ASCT and one patient (primary progressive MS) - salvage HDCT+ASCT. Median EDSS at base-line was 6.0 (range 2.0 – 7.5). The median follow-up duration was 12 months (range 6 – 72 months). All of the patients had previously undergone conventional treatment. Neurological and QoL evaluation was provided at baseline, at discharge, 3, 6, 9, 12 months, and then every 6 months. MRI was conducted at baseline, at 6, 12 months, and at the end of follow-up. FACT-BMT and FAMS were used for QoL evaluation. QoL response was evaluated using Integral QoL index, which was calculated by the method of integral profiles. 14 (82.4%) out of 17 patients including 12 patients with conventional HDCT+ ASCT, one patient with early HDCT+ ASCT and one patient with salvage HDCT+ ASCT experienced a clinical stabilization or improvement. Three patients showed significant improvement in EDSS (by more than 1.0 point), 2 patients improved by 1.0, and 3 patients - by 0.5. Six cases remained stable. All of the patients with clinical stabilization and improvement exhibited negative MRI scans. One patient continuously worsened and died 3 years after the transplantation. Two other patients worsened by 0.5 points in their EDSS. All patients with clinical response exhibited improved QoL at 6 months post-transplant and they preserved improved QoL at the end of follow-up. At one year after HDCT+ASCT the patients exhibited a good or excellent QoL response. These levels of QoL response were preserved throughout the follow-up period. In conclusion, clinical response was observed in 82.4% MS patients after HDCT+ASCT. Notably, patients undergoing early, conventional and salvage HDCT+ASCT exhibited clinical response. All patients with clinical response had good or excellent QoL response. Thus, HDCT+ASCT appears to be an effective treatment for MS both in terms of clinical and patient-reported outcomes. The data obtained point to feasibility of early, conventional and salvage HDCT+ASCT in MS patients. Further studies should be done to investigate clinical and QoL response in MS patients receiving early, conventional and salvage HDCT+ASCT to better define treatment success.

The population of new ANHL patients is heterogeneous in terms of their biological parameters and the IPI scoring system is widely used to make the disease prognosis. Recently heterogeneity of ANHL patients in terms of their QoL has been shown. There are four groups of patients with the following grades of QoL impairment: none, mild, significant, and critical impairment. We aimed to study the distribution of new ANHL patients according to the grades of QoL impairment and to identify the relationship between the QoL impairment groups and the IPI groups. 73 new aggressive NHL lymphoma patients (Stage IIB-IV, mean age 55.2 SD=17.6, males/females – 39/34) were involved in this study. QoL assessment was conducted before treatment using SF-36. The method of integral profiles was used to calculate the integral QoL index (IQLI). Patients were stratified using IQLI. Gamma correlation between ranges of QoL impairment groups and IPI groups was used. The following distribution of ANHL patients was demonstrated on the basis of different grades of QoL impairment: 9% - no impairment (IQLI - 0.6); 12% - mild impairment (0.3); 24% - significant impairment (0.13); 55% - critical impairment (0.02). The distribution of patients in these groups who were classified as high-intermediate or high risk according to the IPI was 28%, 67%, 83%, and 90%, respectively. High correlation between ranges of QoL impairment groups and IPI groups was observed: Gamma correlation – 0.6 (p In conclusion, aggressive NHL patients are heterogeneous in terms of their QoL. The majority of patients exhibit significant or critical QoL impairment. The higher the grade of QoL impairment, the higher the risk according to the IPI. Stratification of aggressive NHL patients based on IQLI along with the traditional IPI stratification could contribute to the improvement of the prognostic model for this heterogeneous group of lymphoid malignancies.

Objectives: HDCT+ASCT is a new and promising therapy for MS patients. Among a number of questions are the terms of conducting HDCT+ASCT. According to our concept there are 3 strategies of HDCT+ASCT depending on terms of disease stage: early, conventional and salvage. The aim of the research was to study clinical and quality of life (QoL) outcomes in MS patients with different terms of HDCT +ASCT. Methods: Twelve patients with MS were included in the study. All the patients previously underwent conventional treatment. Clinical and QoL evaluation was provided at baseline, at discharge, at 3, 6, 9, 12 months and later every half a year after HDCT+ ASCT. MRI was conducted at baseline, in 6, 12 months and at the end of follow-up. QoL was assessed by FACT-BMT and FAMS. Integral QoL index was assessed by the method of integral profiles. Median EDSS at base-line was 6.0 (range 2 –7.5). The median follow-up duration was 18 months (range 3–60 months). Results: Clinical examination and MRI revealed disease stabilization (DS) in ten patients and progression (DP) in two patients. EDSS decreased in seven patients; increased from 6.5 to 7.0 and from 6.0 to 6.5 in patients with DP and remained the same in three patients. Distinct QoL improvement was observed in all the patients with DS at the end of follow-up. Three case reports with different terms of ASCT were analyzed. Patient K. underwent early ASCT (male, 21 years old; secondary progredient type; base-line EDSS - 2.0; follow-up 18 months); patient F.- conventional ASCT (female, 35 years old; secondary progredient type; base-line -EDSS 5.0; follow-up 60 months); patient P.- salvage ASCT (female, 49 years old; secondary progredient type; base-line EDSS 7.5; follow-up 48 months). Clinical examination and MRI revealed DS. EDSS decreased from 2.0 to 1.5 in patient K.; from 5.0 to 4.5 in patient F. and from 7.5 to 6.0 in patient P. at the end of follow-up. Integral QoL index increased dramatically as compared to base-line: in patient K. - from 0.6 to 0.7; in patient F. - from 0.2 to 0.7; in patient P. - 0.4 to 0.6. Conclusion: HDCT+ASCT in MS patients resulted in DS in ten out of twelve patients under observation. Along with clinical stabilization dramatic improvement of QoL took place. Analysis of three case reports demonstrated feasibility of early, conventional and salvage ASCT in MS patients.

Background: It is quite obvious that population of new Hodgkin’s disease (HD) patients is heterogeneous in terms of clinical characteristics. Therefore stratification of patients is necessary to select appropriate treatment regimen. It was shown that new lymphoma patient population is heterogeneous in terms of base-line QoL (Novik A et al, 2003). The aim of the study was to identify if new HD patients are heterogeneous in terms of QoL and to stratify patients using QoL parameters. Patients and methods: 114 new HD patients (stage IIB-IV, mean age 30.2 (SD 13.5), males/females - 55/59) were enrolled in the study. Patients filled in EORTC QLQ-C30 at baseline. The method of integral profiles (MIP) was used to calculate integral QoL index (IQL), the coefficient of QoL deformation (CQLD) and the index of symptom severity (ISS). The above indexes were used for stratification by the cluster analysis (Ward method, percent of cases correctly classified - 98.25%). Discriminant analysis was performed for stratification testing. Results: Three groups of HD patients were identified after stratification. IQL, CQLD and ISS were as follows: subgroup 1 (n=5, mean age 40.8 (22.9), male/female 1/4) − 0.04, 1.7, 0.17; subgroup 2 (n=47, mean age 34.3 (14.5), male/female 23/24) − 0.35, 0.62, 0.09; subgroup 3 (n=62; mean age 26.0 (9.7); male/female 31/31) − 0.74, 0.24, 0.01. Group 1 has the worst QoL and is characterized by low IQL, pronounced symptoms and high deformation of QoL profile. Group 3 has the best QoL with high IQL, weak symptoms and low deformation of QoL profile. Group 2 has intermediate values of above parameters. Differences between groups were significant (p Conclusion: The method of integral profiles to obtain the integral QoL index and the coefficient of QoL deformation in HD patients is proposed. Stratification of new HD patients by cluster analysis resulted in three patient subgroups according to their QoL data. Identification of subgroups of HD patients on the basis of their QoL has a good potential for better stratification of new HD patients and in doing so might be used for improvement of the intervention strategies.