Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.
- MeSH
- akutní lymfatická leukemie * etiologie MeSH
- busulfan * analogy a deriváty MeSH
- dítě MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * etiologie MeSH
- předškolní dítě MeSH
- příprava pacienta k transplantaci škodlivé účinky MeSH
- recidiva MeSH
- thiotepa terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
Jako standardní přípravný režim se před podáním autologní transplantace krvetvorných buněk (ASCT) u relabujících či refrakterních lymfomů používal BEAM, tedy carmustine (BCNU) v kombinaci s etoposidem, cytarabinem a melfalanem. Recentní nedostatek BCNU však vedl k nutnosti přechodu na alternativní režim, kterým se v našem centru stal od července 2018 režim obsahující thiotepu, tzv. TEAM. Rozhodli jsme se retrospektivně srovnat gastrointestinální (GIT) toxicitu obou přípravných režimů. Zahrnuli jsme 142 konsekutivně autologně transplantovaných pacientů (BEAM = 82, TEAM = 60), z nichž 31 % mělo difuzní velkobuněčný B-lymfom (DLBCL), 20 % Hodgkinův lymfom (HL), 15 % lymfom z plášťových buněk (MCL), 14 % T-buněčné lymfomy (T-NHL) a zbylých 20 % ostatní druhy non-Hodgkinových lymfomů (NHL). Obě kohorty byly srovnatelné stran věku pacientů, zastoupení diagnóz a stavu nemoci v době ASCT. V distribuci jednotlivých stupňů GIT toxicity nebyl mezi dvěma přípravnými režimy nalezen statisticky signifikantní rozdíl, a to ani po seskupení všech stupňů do dvou hlavních skupin pacientů (grade 0 + 1 vs. grade 2–4). Pacienti dostávající režim TEAM však častěji dospěli k potřebě parenterální výživy, a to ve 20 případech (33 %) oproti pouhým 13 případům (16 %) u režimu BEAM (p = 0,04). Nerelapsová mortalita (NRM) byla u obou režimů srovnatelně nízká, během hospitalizace byla 0 %, ve 3 měsících pak 2 % shodně pro oba přípravné režimy (p = 1,0). Nezaznamenali jsme statisticky signifikantní rozdíl v celkovém přežití (overal survival; OS) ani v přežití do známek progrese (progression free survival; PFS) (p = 0,59 pro OS, p = 0,1 pro PFS).
The BEAM regimen, i.e., carmustine (BCNU) in combination with etoposide, cytarabine, and melphalan was used as standard conditioning prior to autologous hematopoietic cell transplantation (ASCT) in relapsed or refractory lymphomas. However, the recent unavailability of BCNU necessitated the use of an alternative regimen, which in our centre became from July 2018 the so-called TEAM regimen containing thiotepa. We decided to retrospectively compare the gastrointestinal (GIT) toxicity of both conditioning regimens. We included 142 consecutive autologous transplant patients (BEAM = 82, TEAM = 60), of whom 31% had diffuse large B-cell lymphoma (DLBCL), 20% Hodgkin‘s lymphoma (HL), 15 % mantle cell lymphoma (MCL), 14% T-cell lymphomas (T-NHL) and the remaining 20% other types of non-Hodgkin lymphomas (NHL). Both cohorts were comparable in terms of patient age, prevalence of diagnoses, and disease status at the time of ASCT. There was no statistically significant difference in the distribution of the grades of GIT toxicity between the two cohorts, even after grouping all grades into two main groups of patients (grade 0+1 vs. grade 2–4). Patients receiving the TEAM regimen were more likely to require parenteral nutrition, namely in 20 cases (33%) versus only 13 cases (16%) in the BEAM regimen (P = 0.04). Non-relapse mortality (NRM) was comparably low for both regimens – 0% during hospitalization and 2% at 3 months for both conditioning regimens (P = 1.0). We also compared overall survival (OS) and progression-free survival (PFS): there was no statistically significant difference between the two cohorts (P = 0.59 for OS, P = 0.1 for PFS).
- MeSH
- autologní transplantace MeSH
- dospělí MeSH
- karmustin škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie metody škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom * farmakoterapie MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- příprava pacienta k transplantaci * metody škodlivé účinky statistika a číselné údaje MeSH
- protinádorové látky škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- thiotepa škodlivé účinky terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.
- MeSH
- akutní lymfatická leukemie * komplikace terapie MeSH
- akutní myeloidní leukemie * terapie MeSH
- busulfan škodlivé účinky MeSH
- celotělové ozáření škodlivé účinky MeSH
- dospělí MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * etiologie MeSH
- příprava pacienta k transplantaci metody MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- thiotepa škodlivé účinky MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- vidarabin analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
- MeSH
- akutní lymfatická leukemie patologie terapie MeSH
- busulfan aplikace a dávkování analogy a deriváty MeSH
- celotělové ozáření mortalita MeSH
- chemoradioterapie mortalita MeSH
- dítě MeSH
- etoposid aplikace a dávkování MeSH
- hodnocení ekvivalence jako téma MeSH
- lidé MeSH
- mezinárodní agentury MeSH
- míra přežití MeSH
- mladiství MeSH
- následné studie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- thiotepa aplikace a dávkování MeSH
- vidarabin aplikace a dávkování analogy a deriváty MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I-IV and 26.6% for grades II-IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.
- MeSH
- busulfan analogy a deriváty MeSH
- dítě MeSH
- hematologické nádory * terapie MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * MeSH
- příprava pacienta k transplantaci * MeSH
- thiotepa MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- vidarabin analogy a deriváty MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Východiská: Leptomeningeálne metastázy (LM) karcinómu prsníka sú asociované s nepriaznivou prognózou. Hoci žiadna randomizovaná štúdia nepotvrdila, že intratekálna liečba predlžuje prežívanie, táto liečba je považovaná za štandard. Prognóza pacientov s LM je nepriaznivá, s mediánom celkového prežívania menej ako 6 mesiacov. Metódy: V tejto kazuistike uvádzame prípad mladej ženy s karcinómom prsníka s LM v čase recidívy, liečenej dvoma líniami intratekálnej chemoterapie s predĺženým prežívaním. Výsledky: Dvadsaťosemročnej žene bez pozoruhodnej anamnézy bol diagnostikovaný triple-negatívny invazívny duktálny karcinóm. Osem mesiacov po adjuvantnej terapii sa rozvinuli mnohopočetné mozgové metastázy a následne 1 mesiac po ukončení rádioterapie na centrálny nervový systém sa vyvinuli nové LM. Iniciálne bola liečená kombináciou metotrexát, cytarabín a dexametazón intratekálne, ale po 3 mesiacoch u pacientky došlo k zhoršeniu klinického stavu a vzostupu nádorových buniek v likvore. Následne dostala kombináciu tiotepy a metotrexátu intratekálne s predĺžením odpovede v trvaní 10 mesiacov. Pacientka zomrela 32 mesiacov od stanovenia diagnózy a 18 mesiacov od infiltrácie leptomenigov v dôsledku progresie ochorenia v pečeni a pľúcach ako aj v leptomeningoch. Záver: Prognóza pacientov s LM zostáva nepriaznivá v dôsledku limitovanej účinnosti súčasne dostupných látok používaných v intratekálnej liečbe, avšak intratekálna chemoterapia by mohla podstatne predĺžiť prežívanie u vybraných pacientov.
Background: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months. Methods: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival. Results: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM. Conclusion: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.
- MeSH
- dospělí MeSH
- lidé MeSH
- meningeální nádory * farmakoterapie sekundární MeSH
- metastázy nádorů MeSH
- nádory prsu * farmakoterapie MeSH
- protokoly protinádorové léčby MeSH
- smrt MeSH
- thiotepa terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Bezpečnost potravin může ovlivnit mnoho různých faktorů, jedním z nich jsou i výrobky, které jsou určeny pro styk s potravinami. Materiály a předměty, které přichází do styku s potravinami, musí být vyrobeny v souladu se správnou výrobní praxí a musí splňovat hygienické požadavky. Do potravin nesmí uvolňovat své složky a tím nepříznivě ovlivnit bezpečnost a kvalitu potravin. Pokud tyto výrobky nevyhovují požadavkům platné legislativy, mohou být jedním ze zdrojů kontaminace potravin a následného ohrožení zdraví spotřebitelů. V tomto článku je uveden přehled materiálů, které se nejčastěji používají k výrobě kuchyňského nádobí a náčiní a zdravotní rizika z kontaminace potravin chemickými látkami, uvolňujícími se z materiálu nádobí. Dále jsou zmíněny případy přenosu rizikových látek z kuchyňského nádobí a náčiní do potravin, zjištěné v Moravskoslezském kraji, České republice a v zahraničí..
Safety of food can be influenced by many factors, including articles intended to come into contact with food. Materials and subjects which come into contact with food must be produced according to good manufacturing practice and must fulfill hygienic requirements. They cannot release their components into food and by this negatively influence safety and quality of food. If these articles do not fulfill requirements of valid legislation, they can be one of the sources of food contamination and following threat to life of consumers. In this article, there is a list of materials which are most commonly used for production of kitchen utensils and medical risks of food contamination by chemicals released from the material of the utensils. Further in the article there are cases of transfer of hazardous substances from kitchen utensils into food in the Moravian-Silesian region, the Czech Republic and abroad.
Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.
- MeSH
- autologní štěp MeSH
- cytarabin aplikace a dávkování MeSH
- dospělí MeSH
- karmustin aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom mortalita terapie MeSH
- melfalan aplikace a dávkování MeSH
- míra přežití MeSH
- mladiství MeSH
- podofylotoxin aplikace a dávkování MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování MeSH
- registrace * MeSH
- retrospektivní studie MeSH
- senioři MeSH
- thiotepa aplikace a dávkování MeSH
- transplantace kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.
- MeSH
- aplikace intravezikální MeSH
- časové faktory MeSH
- doxorubicin aplikace a dávkování analogy a deriváty MeSH
- epirubicin aplikace a dávkování MeSH
- karcinom z přechodných buněk mortalita patologie terapie MeSH
- lidé MeSH
- lokální recidiva nádoru prevence a kontrola MeSH
- míra přežití MeSH
- mitomycin aplikace a dávkování MeSH
- nádory močového měchýře mortalita patologie terapie MeSH
- progrese nemoci MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování MeSH
- randomizované kontrolované studie jako téma MeSH
- rizikové faktory MeSH
- staging nádorů MeSH
- thiotepa aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
