This phase 3 study evaluated the efficacy and safety of the new hypomethylating agent guadecitabine (n = 408) vs a preselected treatment choice (TC; n = 407) of azacitidine, decitabine, or low-dose cytarabine in patients with acute myeloid leukemia unfit to receive intensive induction chemotherapy. Half of the patients (50%) had poor Eastern Cooperative Oncology Group Performance Status (2-3). The coprimary end points were complete remission (19% and 17% of patients for guadecitabine and TC, respectively [stratified P = .48]) and overall survival (median survival 7.1 and 8.5 months for guadecitabine and TC, respectively [hazard ratio, 0.97; 95% confidence interval, 0.83-1.14; stratified log-rank P = .73]). One- and 2-year survival estimates were 37% and 18% for guadecitabine and 36% and 14% for TC, respectively. A large proportion of patients (42%) received <4 cycles of treatment in both the arms. In a post hoc analysis of patients who received ≥4 treatment cycles, guadecitabine was associated with longer median survival vs TC (15.6 vs 13.0 months [hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; log-rank P = .02]). There was no significant difference in the proportion of patients with grade ≥3 adverse events (AEs) between guadecitabine (92%) and TC (88%); however, grade ≥3 AEs of febrile neutropenia, neutropenia, and pneumonia were higher with guadecitabine. In conclusion, no significant difference was observed in the efficacy of guadecitabine and TC in the overall population. This trial was registered at www.clinicaltrials.gov as #NCT02348489.

• MeSH
• akutní myeloidní leukemie * diagnóza   farmakoterapie   MeSH
• azacytidin * škodlivé účinky   MeSH
• cytarabin škodlivé účinky   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• akutní myeloidní leukemie * terapie   MeSH
• analýza přežití MeSH
• homologní transplantace metody   trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• statistika jako téma MeSH
• transplantace kmenových buněk * metody   trendy   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

• MeSH
• akutní myeloidní leukemie * farmakoterapie   MeSH
• azacytidin * terapeutické užití   MeSH
• bicyklické sloučeniny heterocyklické terapeutické užití   MeSH
• lidé MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• sulfonamidy terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS were significantly younger with more severe cytopenias, and cytogenetic differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q), del(16q), and del(20q). Although differences in time to acute myeloid leukemia transformation did not occur, a significantly better survival in JPN was demonstrated, even after the adjustment for age and FAB subtypes, especially in lower, but not in higher prognostic risk categories. Certain clinical factors (cytopenias, blast percentage, cytogenetic risk) had different impact on survival and time to transformation to leukemia between the two groups. Although possible confounding events (e.g., environment, diet, and access to care) could not be excluded, our results indicated the existence of clinically relevant ethnic differences regarding survival in MDS between JPN and CAUC patients. The good performance of the IPSS-R in both CAUC and JP patients underlines that its common risk model is adequate for CAUC and JP.

• MeSH
• Asijci * MeSH
• běloši * MeSH
• lidé MeSH
• míra přežití MeSH
• myelodysplastické syndromy * diagnóza   etiologie   genetika   mortalita   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

• MeSH
• antitumorózní látky ekonomika   terapeutické užití   MeSH
• chemorezistence MeSH
• chronická myeloidní leukemie * diagnóza   terapie   MeSH
• cílená molekulární terapie MeSH
• diferenciální diagnóza MeSH
• filadelfský chromozom MeSH
• incidence MeSH
• inhibitory proteinkinas ekonomika   terapeutické užití   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• nádorové biomarkery MeSH
• náklady na léky MeSH
• předpověď MeSH
• randomizované kontrolované studie jako téma MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk MeSH
• záchranná terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

A study comparing the use of Blinatumomab and standard chemotherapy in the treatment of acute lymphoblastic leukemia. Intended for professional public.

• Klíčová slova
• Blinatumomab,
• MeSH
• akutní lymfatická leukemie MeSH
• antitumorózní látky MeSH
• monoklonální protilátky MeSH
• protilátky bispecifické MeSH
• Publikační typ
• srovnávací studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• farmakoterapie
• onkologie
• hematologie a transfuzní lékařství

Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990-2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment. The overall complete remission rate after first salvage was 40%, ranging from 35%-41% across disease status categories (primary refractory, relapsed with or without prior transplant), and was lower after second (21%) and third or greater (11%) salvage. The overall complete remission rate was higher for patients diagnosed from 2005 onward (45%, 95% CI: 39%-50%). One- and three-year survival rates after first, second, and third or greater salvage were 26% and 11%, 18% and 6%, and 15% and 4%, respectively, and rates were 2%-5% higher among patients diagnosed from 2005. Prognostic factors included younger age, longer duration of first remission, and lower white blood cell counts at primary diagnosis. This large dataset can provide detailed reference outcomes for patients with relapsed/refractory Ph-negative B-precursor acute lymphoblastic leukemia. clinicaltrials.gov identifier: 02003612.

• MeSH
• analýza přežití MeSH
• chemorezistence MeSH
• dospělí MeSH
• filadelfský chromozom * MeSH
• indukce remise MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• opakovaná terapie MeSH
• pre-B-buněčná leukemie diagnóza   genetika   mortalita   terapie   MeSH
• prognóza MeSH
• průzkumy zdravotní péče MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• MeSH
• anemie * MeSH
• leukopenie MeSH
• lidé MeSH
• myelodysplastické syndromy * MeSH
• trombocytopenie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.

• MeSH
• časové faktory MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• myelodysplastické syndromy mortalita   MeSH
• nádorová transformace buněk patologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: In a Phase III trial, 485 patients (≥65 years) with newly diagnosed acute myeloid leukemia received decitabine 20 mg/m(2) intravenously for 5 days every 4 weeks or a treatment choice (supportive care or cytarabine 20 mg/m(2) subcutaneously for 10 days every 4 weeks). MATERIALS AND METHODS: We summarized overall and progression-free survival by baseline white blood cell count using two analyses: <1, 1-5, >5×10(9)/L; ≤10 or >10×10(9)/L. RESULTS: There were 446 deaths (treatment choice, n=227; decitabine, n=219). Median overall survival was 5.0 (treatment choice) versus 7.7 months (decitabine; nominal P=0.037). Overall survival differences between white blood cell groups were not significant; hazard ratios (HRs) favored decitabine. Significant progression-free survival differences favored decitabine for groups 1-5×10(9)/L (P=0.005, HR =0.67), greater than 5×10(9)/L (P=0.027, HR =0.71), and up to 10×10(9)/L (P=0.003, HR =0.72). CONCLUSION: There was a trend toward improved outcome with decitabine, regardless of baseline white blood cell count.

• Publikační typ
• časopisecké články MeSH