PurposeTo compare the impact of a single fraction (8 Gy × 1 fraction) and multifraction (3 Gy × 10 fractions) radiotherapy regimens on pain relief, recalcification and the quality of life (QoL) in patients with bone destructions due to multiple myeloma (MM).Patients and methodsIn all, 101 patients were included in a randomised prospective clinical trial: 58 patients were included in the control arm (3 Gy × 10 fractions) and 43 patients into the experimental arm (8 Gy × 1 fraction). The response rate was defined according to the International Consensus on Palliative Radiotherapy criteria. Recalcification was evaluated with radiographs. QoL questionnaires were completed before and 4 weeks after treatment.ResultsPain relief was obtained in 81/101 patients (80.2%): complete response in 56 (69%) and partial in 25 patients (30.9%). No significant differences were observed in analgesic response between the groups. Significant factors for pain relief were female gender, age under 65, IgG MM type, presence of recalcification at the irradiated site. Recalcification was found in 32/101 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). No significant differences were observed in recalcification between the groups. Significant factors for recalcification were Karnofsky index ≥ 60%, haemoglobin level ≤ 80 g/dl, MM stage II and analgesic response at the irradiated site. The QoL after radiotherapy was improved in the control group.ConclusionThe same analgesic and recalcification response was observed using two different radiotherapy regimens. Higher doses should be used to achieve a better QoL.

HSCT is the only curative option for many malignant and non-malignant diseases. The WBMT was founded as an umbrella organization of societies involved in cellular therapies with the mission of promoting excellence in HSCT. As a non-governmental organization in official relation with the World Health Organization (WHO), the WBMT assisted in the founding of regional societies (Latin America Blood and Marrow Transplantation Group and African Blood and Marrow Transplantation Group), performs global activity surveys, conducts workshops and provides expert support for programs in evolving countries. In this retrospective evaluation we analyzed worldwide activity trends in HSCT up to the year 2016 and evaluated possibilities of improving availability of HSCT by the use of telemedicine. Methods: HSCT activity was collected annually from member societies, national registries and individual centers including donor type (allogeneic/autologous), stem cell source (bone marrow/peripheral blood stem cells/cord blood) and indications for transplant. Transplant rates (TR) were calculated as HSCT/10 million inhabitants without adjustment for patients transplanted in a country other than that of primary residence. Country team density (TD) was defined as teams/10 million inhabitants. Workshops were organized in a number of locations where there was little or no HSCT activity or where improvement in one or more aspect of local or regional HSCT activity was requested, including Vietnam, Brazil, China, South Africa and Morocco. Other countries were paired with established centers using WBMT affiliated partners. In two countries, a pilot program was established involving a 6 month physician training in a JACIE/FACT accredited center followed by daily telemedicine-guided supervision of clinical activities. Results: From 1957-2016 a total of 1,298,897 HSCT (57.1% autologous) procedures were collected. By the end of 2016, HSCT activity was reported from 87 of the 195 WHO member states. A total of 89,070 HSCT from 1662 centers was reported in 2016. Assuming a frequency of 84,000/year, 1.5 million HSCT will be reached in 2019, only 7 years after the 1 million report in 2012 (Figure 1). The global activity/year increased continuously from 10,000/year in 1991 to 82,718 first HSCT/year in 2016 with a global increase of >7% (7.0% in autologous and 7.8% in allogeneic HSCT). As in previous years, slightly more autologous (53.5%) than allogeneic and more related (53,6%) than unrelated HSCT were reported. The further increase in related HSCT was caused mainly by an increase of non-identical family donors (39.5% of related HSCT). Increase in activities according to regions is given in Figure 2. TR and TD varied according to region and are highest in Nord America with 511.2 TR, followed by Europe with 390.9 TR, Latin America with 63.9 TR, APBMT with 46.2 TR and Africa/EMRO with 32.8 TR. In contrast, TD was highest in Europe (7.5 TD) followed by Nord America (6.0 TD), APBMT (1.9 TD), Latin America (1.9 TD) and Africa/EMRO (0.4 TD). Commonest indications were lymphoproliferative diseases for autologous and leukemia for allogeneic HSCT and continue to rise (Figure 3 autologous and Figure 4 allogeneic HSCT). Graft source were predominantly peripheral blood in autologous (99.7%) and 65% in unrelated HSCT, while umbilical cord blood as a stem cell source (13.8% of all unrelated) declined. More than 150 HSCT were performed in one country and one center without activities using daily telemedicine-guided supervision. In conclusion, the global distribution and activities are increasing continuously by more than 7,0% per year with numbers currently running at app. 90,000/year. Of note is the increase of haploidentical HSCT activity, while the use of umbilical cord blood HSCT continues to decrease. TR data show significant gaps between regions. Supervisory telemedicine is a powerful tool to overcome lack of experience and establish JACIE/FACT compatible new programs with collateral benefits for conventional hematology, blood banking, microbiology and virology. Abbreviations: EUR, Europe; AMR/PHA, America; SEAR/WPR, South-East Asia/Western Pacific; AFR/EMRO, African/Eastern Mediterranean. Disclosures Niederwieser: Daichii: Speakers Bureau; Cellectis: Consultancy. Atsuta:Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Mochida Pharmaceutical Co. Ltd: Honoraria; Janssen Paharmaceutical K.K.: Honoraria. Worel:Sanofi Genzyme, Malinckrodt Therakos: Research Funding; Jazz, Sanofi, Celgene, Novartis, Malinckrodt Therakos: Honoraria; Sanofi Genzyme, Malinckrodt Therakos: Speakers Bureau. Galeano:Szabo SA: Other: (Equity interest). Novitzky:Astellas, Roche: Consultancy. Szer:Prevail Therapeutics: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Weisdorf:Incyte: Research Funding; Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy. Pasquini:Amgen: Consultancy; BMS: Research Funding; Medigene: Consultancy; Pfizer: Other: Advisory Board; Novartis: Research Funding; Kit Pharma: Research Funding.

Reference intervals for two well-recognized tests for the lupus anticoagulant were determined using 98 healthy subjects. The purpose of the study was to compare the reference intervals for the dilute tissue thromboplastin inhibition test on this group of healthy subjects calculated by parametric and nonparametric statistical methods, and to compare these results with results obtained on subsets of 20 and 40 randomly selected individuals from the group of 98. The same procedures were followed for the dilute Russell's viper venom test. Results were recorded in seconds of clotting times and in ratios (subject/mean of that set or subset). Statistical analysis revealed Gaussian distribution of the results in the large group as well as in each subset for both tests. The results showed more variation between sets of the dilute tissue thromboplastin inhibition test than of the dilute Russell's viper venom test. Nonparametrically calculated reference intervals were wider than those determined by the parametric method, especially if confidence intervals are provided for both reference limits in a group of 94 controls or in a subset of 40 subjects. The nonparametric technique uses all data for the calculation of reference interval of such sample sizes no matter how widely spread the results are. There was no significant difference between the reference intervals of subsets and the whole group (p > 0.05) calculated by both statistical techniques. Very few outliers were observed among these subjects in both tests.

BackgroundCurrently available chronic myeloid leukaemia (CML) survival reports have originated from more affluent countries. Herein we report the entire country data on incidence and survival of CML, as well as penetrance of tyrosine kinase inhibitors (TKIs) in Lithuania.MethodsWe analyzed all patients (N = 601) from the national haematological disease monitoring system who were diagnosed with CML between 2000 and 2013. Crude (CR) and age-standardized (weighted) (ASW(R)) incidence and mortality rates, as well as 1-, 5-, and 10-year relative survival rates (RSR) were calculated. Information on TKI penetration is also reported.ResultsThroughout the entire 2000–2013 period the median age at diagnosis of CML patients was 62 years. The respective incidence and mortality CRs were 1.28 and 0.78, both characterized by decreasing trends over the observation period. A 5-year RSR increased from 0.33 [95 % CI, 0.27–0.40] in 2000–2004 to 0.55 [95 % CI, 0.47–0.63] in 2005–2009. However, the respective 5-year RSRs for patients aged 65–74 and ≥75 were only 0.33 [95 % CI, 0.24–0.42] and 0.18 [95 % CI 0.07–0.23] during the entire study period. TKI penetrance for CML patients grew from 1.5 % in 2000–2004 to 30.6 % in 2005–2009 and 69.1 % in 2010–2013. TKI penetrance was low in the older age groups (60 % for the 65–74 and 19 % for the ≥75 patient group, in 2010–2013).ConclusionRelative CML survival in Lithuania steadily improved and paralleled the increase in TKI treatment availability. Patients above 64 years rarely received TKIs and their relative survival remained low throughout the observation period. The latency of TKI availability may have influenced the survival trends.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2238-9) contains supplementary material, which is available to authorized users.

Adult acute lymphoblastic leukemia (ALL) is characterized by a high frequency of abnormal karyotypes some of which are related to outcome. Single nucleotide polymorphism (SNP) array analysis provides a highly sensitive platform to detect large and small genomic aberrations. SNP array profiling data in adult ALL are limited and further systematic studies of this patient group are needed. We performed a population-based SNP array analysis of genomic aberrations and their influence on survival in 66 Lithuanian 18-65 year old ALL patients diagnosed between 2007 and 2013. Most aberrations were detected in chromosome arm 9p, chromosome arm 6q, chromosome arm 13q, and chromosome 17. The recurrently targeted copy number abnormalities involved several leukemia-related genes-CDKN2A/B, MLL, IKZF1, PAX5, RB1, TP53, and ETV6. We identified several new recurrent aberrations with possible new target genes: SMARCA4 in 19p13.2, RNASEL in 1q25.3, ARHGEF12 in 11q23.3, and LYL1 in 19p13.2. Aberrations in chromosome 13 and the RB1 gene as well as CDKN2A/B gene status were related to the outcome.