- Klíčová slova
- nilotinib, bosutinib, ponatinib,
- MeSH
- aniliny aplikace a dávkování terapeutické užití MeSH
- chinoliny aplikace a dávkování terapeutické užití MeSH
- chronická fáze myeloidní leukemie terapie MeSH
- chronická myeloidní leukemie * terapie MeSH
- dasatinib aplikace a dávkování terapeutické užití MeSH
- imatinib mesylát aplikace a dávkování terapeutické užití MeSH
- imidazoly aplikace a dávkování terapeutické užití MeSH
- inhibitory proteinkinas aplikace a dávkování terapeutické užití MeSH
- inhibitory tyrosinkinasy aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli MeSH
- nitrily aplikace a dávkování terapeutické užití MeSH
- pyridaziny aplikace a dávkování terapeutické užití MeSH
- pyrimidiny aplikace a dávkování terapeutické užití MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- Check Tag
- lidé MeSH
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups.
Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.
- MeSH
- chronická lymfatická leukemie * terapie MeSH
- COVID-19 * etiologie MeSH
- homologní transplantace metody MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- příprava pacienta k transplantaci metody MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Therapeutic management of patients with primary or secondary myelofibrosis (MF) who experience relapse or graft failure following allogeneic haematopoietic cell transplantation (allo-HCT) remains heterogeneous. We retrospectively analyzed 216 patients undergoing a second allo-HCT for either relapse (56%) or graft failure (31%) between 2010 and 2017. Median age was 57.3 years (range 51-63). The same donor as for the first allo-HCT was chosen in 66 patients (31%) of whom 19 received an HLA-identical sibling donor, whereas a different donor was chosen for 116 patients (54%). Median follow-up was 40 months. Three-year overall survival (OS) and relapse-free survival (RFS) were 42% and 39%, respectively. Three-year non-relapse mortality (NRM) and relapse rates were 36% and 25%, respectively. Grade II-IV and III-IV acute GVHD occurred in 25% and 11% of patients, respectively, and the 3-year incidence of chronic GVHD was 33% including 14% for extensive grade. Graft-failure incidence at 1 year was 14%. In conclusion, our data suggest that a second allo-HCT is a potential option for patients failing first allo-HCT for MF albeit careful patient assessment is fundamental to identify individual patients who could benefit from this approach.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory * MeSH
- nemoc štěpu proti hostiteli * MeSH
- primární myelofibróza * terapie MeSH
- příprava pacienta k transplantaci MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. METHOD: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). RESULTS: The length of induction treatment required to achieve a Good response did not affect PFS (P = .65) or OS (P = .61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P = .31), and median OS 81.7, 92.7, and 77.4 months, respectively (P = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P-value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant. CONCLUSION: The kinetics of response did not affect outcomes.
- MeSH
- autologní transplantace MeSH
- časové faktory MeSH
- indukce remise MeSH
- lidé MeSH
- mnohočetný myelom diagnóza mortalita terapie MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky metody MeSH
- trvání terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chinazolinony MeSH
- folikulární lymfom * terapie MeSH
- lidé MeSH
- puriny MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
Several novel therapies have been licensed for the treatment of myeloma in recent years. We summarize some of the trials leading to their approval and the current evidence for their clinical use. A number of promising agents undergoing phase I/II trial evaluation are also discussed. RECENT FINDINGS: The immunomodulatory drugs, thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib, have been shown to be effective agents, both alone and as part of combination regimens, for the treatment of myeloma. Studies are now focusing on the optimal sequencing of these drugs throughout the disease course, with a view to maximizing antitumor efficacy and minimizing overlapping toxicities. New protocols are increasingly based on preclinical evidence of synergy. The incorporation of these agents into transplant-based treatment protocols has improved outcomes. Other examples of novel agents undergoing assessment at present include arsenic trioxide, hsp90 inhibitors and histone deacetylase inhibitors. Future developments are likely to include individualized treatment plans based on patient-specific parameters including cytogenetic analysis and gene expression profiling. SUMMARY: Thalidomide, lenalidomide and bortezomib can now be considered as standard options both as first-line agents and beyond for the treatment of myeloma, with respective combinations also emerging as valid choices for all stages of the disease.
- MeSH
- antitumorózní látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- imunosupresiva aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kyseliny boronové aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- mnohočetný myelom farmakoterapie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- pyraziny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- thalidomid analogy a deriváty aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
