Mass Spectrometry-Based Assessment of M-protein in Peripheral Blood During Maintenance Therapy in Multiple Myeloma.

Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during post-transplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of post-transplant maintenance with either carfilzomib, lenalidomide, dexamethasone or lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in PB in the post-transplant setting, despite unavailability of pre-treatment calibration samples. There was high agreement between MRD by MS in PB and paired BM MRD results at the 10-5 threshold, assessed by either next generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which in landmark analysis reached statistical significance after 18 cycles post-transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared to MRD negativity by only one modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, post-transplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.

A roadmap for a comprehensive control of cervical cancer in Poland: integration of available solutions into current practice in primary and secondary prevention.

In Poland, cervical cancer incidence and mortality still remain considerably higher than in Western European countries or North America. Recent data indicate decreasing trends in women younger than 60 years and stable trends in older women. In this article, we identified obstacles in primary and secondary prevention of cervical cancer in Poland. We analysed local legislation, management structure and organization of cervical cancer prevention in Poland and reviewed solutions available and implemented in other European countries. The main weaknesses include: (i) very low coverage of organized screening; concurrent unregistered opportunistic screening with unknown coverage and high test consumption (ii) suboptimal quality assurance in organized screening and no external quality assurance in opportunistic screening (iii) very low coverage of human papillomavirus vaccination that is not centrally reimbursed (iv) absence of pilot evaluation of (a) interventions that may improve population coverage and (b) performance of new preventive strategies. The proposed solutions are multifaceted and involve: (i) legislative and organizational regulation of cervical cancer screening aimed at comprehensive registration of procedures, data access and quality assurance (ii) pilot testing and implementation of new ways to increase coverage of cervical cancer screening, in particular among older women (iii) pilot evaluation with possible introduction of human papillomavirus-based screening and (iv) inclusion of human papillomavirus vaccination into the reimbursed national immunization program.

Mapping cancer research across Central and Eastern Europe, the Russian Federation and Central Asia: Implications for future national cancer control planning.

Cancer research is an essential part of national cancer control programmes, and the emerging economies of Central and Eastern Europe (CEE) and the Russian Federation and Central Asia (R-CA) (Commonwealth of Independent States) remain relatively understudied. Here, we map the cancer research activity from the 29 countries across these regions over a 10-year period (2007-2016), using a standard scientometric approach. Research activity was compared with the countries' wealth and with the disease burden from different cancers, and analyses were also performed by the research domain (e.g. fundamental cancer biology, surgery). We found that although there was a correlation between outputs and national wealth, there were many outliers; the CEE countries publishing relatively more, and the R-CA, less. Outputs reflected cancer burdens, but there was a relative paucity of research on lung, colorectal, gastric and pancreatic cancer, as well as research domains such as screening and palliative care. Clinical trials accounted for only 3% of all research outputs from all countries, and were very international, with on average 1.5 CEE countries and 8.0 others involved in each article, and they were heavily cited (on average, 84 times in 5 years). Poland was by far the most research-active country, but significant needs and opportunities have been identified to expand the cancer research activity in all CEE and R-CA countries to enhance national cancer control planning.

Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation.

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and <3 transfusions, ≤21 to 25 days in hospital or ≥7 days on antibiotics and no transfusions; from 21 to 30 days [25 to 34] in hospital), unfavorable (>7 days on antibiotics, >3 but <6 transfusions; >30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 10(6)/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 10(6)/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P < .0001) except acute myelogenous leukemia and acute lymphoblastic leukemia, (3) 1 or 2 aphereses (P = .001) predicted good outcome, (4) toxicity increased with higher graft volume reinfused (>500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care.

Implications of the European Organisation for Research And Treatment Of Cancer (EORTC) guidelines on the use of granulocyte colony-stimulating factor (G-CSF) for lymphoma care.

Febrile neutropenia (FN) is a potentially life-threatening complication of myelosuppressive chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend use of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis if the overall FN risk to a patient is >or=20%, or if a reduction in chemotherapy dose intensity correlates with a poorer outcome. Many of the regimens used for treatment of lymphoma, including R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone), are associated with an FN risk of approximately 20% or higher. Individual patient factors that may increase the risk of FN such as advanced age or advanced disease should be taken into account when assessing the need for G-CSF support. Predictive models are being developed to facilitate individual risk assessment. Additional anti-infective prophylaxis may be indicated in some settings. There is now much evidence for the benefits of G-CSF in reducing the incidence of FN and facilitating delivery of chemotherapy, including dose-escalated and dose-dense (interval-reduced) regimens. If given according to guidelines, G-CSF has the potential to reduce FN and related morbidity. Furthermore, by facilitating delivery of planned chemotherapy, use of G-CSF may potentially influence survival in the curative setting. Implementation of the EORTC guidelines will lead to a greater proportion of patients receiving G-CSFs, but the costs involved should be at least partly offset by a reduction in FN and its associated costs, including those of hospitalization.