Matches in SemOpenAlex for { <https://semopenalex.org/work/W4238079255> ?p ?o ?g. }
Showing items 1 to 98 of
98
with 100 items per page.
- W4238079255 endingPage "1705" @default.
- W4238079255 startingPage "1705" @default.
- W4238079255 abstract "Abstract Background In myelodysplastic syndromes (MDS), abnormalities of chromosome 3 (i.e. inversion 3 (inv(3)), translocation 3q (t(3q)), or deletion 3q (del(3q)) represent a poor-risk karyotype in the Revised International Prognostic Scoring System (IPSS-R). In acute myeloid leukemia (AML) patients with 3q abnormalities, patients with inv(3)/t3;3 represented the most unfavorable group with a median overall survival (OS) of 10.3 months (Lugthart et al., 2010). We previously presented a single institution experience regarding outcomes of MDS patients with chromosome 3 abnormalities. Here, we sought to further define outcomes of chromosome 3 abnormalities in MDS and address the impact of hypomethylating agents (HMA) on outcome in multiple institutions. Patients and Methods Patients were identified through the MDS Clinical Research Consortium and were included if they had a WHO diagnosis of MDS, MDS/myeloproliferative neoplasm (MPN), therapy related MDS (t-MDS), or AML (20-30% myeloblasts) and had any karyotypic abnormality involving chromosome 3. Data analyzed included baseline demographics, disease characteristics, IPSS/IPSS-R scores, treatment and outcome. Responses to HMA therapy were evaluated using International Working Group (IWG) 2006 criteria. Kaplan-Meier estimates were used for overall survival. Results A total of 413 patients were identified with a median age at diagnosis of 67 years. WHO classification was as follows: 9% RA/RARS, 12% RCMD, 26% RAEB-1, 31% RAEB-2, 2% MDS/MPN, 7% MDS Unclassified, 13% AML; 34% had t-MDS. Overall, 97% of patients were higher risk by IPSS-R (i.e., intermediate to very high risk) with a median blast % in bone marrow of 8%. Distribution of cytogenetic abnormalities were inv(3) (10%), del(3q) (12%), t(3q) (18%), monosomy 3 (22%), 3p abnormalities (22%), and other chromosome 3 changes (17%). Median OS for the cohort was 12.0 months (95% C.I. 10.8 to 13.9 months) and 31% of patients without AML transformed to AML. IPSS-R was predictive of median OS across subgroups (P < 0.00001). The specific cytogenetic abnormality was predictive for survival (P < 0.00001) with median OS for t(3q) 19 months, inv(3) 13 months, del(3q) 13 months, 3p 10 months, monosomy 3 9 months, and other 3 abnormalities 11 months. There was no survival difference between patients with translocations of 3q21 versus 3q26 (median OS 18 months versus 18.6 months, P = 0.96). Patients with an isolated chromosome 3 abnormality had significantly improved OS (25.1 months versus 10.9 months (P < 0.00001). Complex karyotype (>/= 3 abnormalities) was observed in 74% of patients and was associated with decreased OS (11 months versus 21 months, P < 0.00001). Of patients who received HMA therapy (48%), the overall response rate was 46% (17% hematological improvement (HI), 7% PR, 20% CR, 2% marrow CR (CRm) with stable disease in 23%). Median OS with and without HMA was 15.5 months versus 8.4 months (p=0.038). In int-2/high risk patients by IPSS, HMA treated patient had a median OS of 14.0 months versus 7.6 months for patients not treated with HMAs (P = 0.005) with no benefit for HMAs in lower-risk patients (median OS 24.5 months with HMA versus 38.7 months without; P =0.41). Cox regression modeling with HMA therapy, IPSS and clinical site confirmed the HMA OS benefit in higher-risk patients (HR 0.69; 95% CI 0.53-0.89; P = 0.005), but showed decreased OS in lower-risk patients (HR 2.0; 95% CI 1.03-3.92; P = 0.04). Allogeneic transplantation was performed in 18% (n=75) of patients, with median OS of 18 months versus 10 months in non-transplanted patients (P < 0.00001). Conclusion In this large cohort of patients with MDS and oligoblastic AML associated with chromosome 3 abnormalities, survival was heterogeneous but overall poor, with isolated chromosome 3 abnormality and t(3q) patients having a more favorable OS than patients with other chromosome 3 anomalies. MDS patients with 3p changes have poor outcomes. Although some patients with chromosome 3 respond to HMA therapy, the overall survival remains poor and novel approaches are needed. Disclosures Sekeres: Amgen: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Steensma:Amgen: Consultancy; Celgene: Consultancy; Incyte: Consultancy; Onconova: Consultancy. Lancet:Boehringer-Ingelheim: Consultancy; Kalo-Bios: Consultancy; Pfizer: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy. List:Celgene Corporation: Honoraria, Research Funding. Komrokji:Incyte: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau." @default.
- W4238079255 created "2022-05-12" @default.
- W4238079255 creator A5010075752 @default.
- W4238079255 creator A5012863731 @default.
- W4238079255 creator A5013240910 @default.
- W4238079255 creator A5020819343 @default.
- W4238079255 creator A5026865748 @default.
- W4238079255 creator A5029369362 @default.
- W4238079255 creator A5035609080 @default.
- W4238079255 creator A5038107984 @default.
- W4238079255 creator A5041443589 @default.
- W4238079255 creator A5041754278 @default.
- W4238079255 creator A5049385583 @default.
- W4238079255 creator A5055740968 @default.
- W4238079255 creator A5061026876 @default.
- W4238079255 creator A5065722106 @default.
- W4238079255 creator A5066001318 @default.
- W4238079255 creator A5085974329 @default.
- W4238079255 creator A5090435894 @default.
- W4238079255 creator A5090527595 @default.
- W4238079255 date "2015-12-03" @default.
- W4238079255 modified "2023-10-16" @default.
- W4238079255 title "Impact of Hypomethylating Agent Therapy in Myelodysplastic Syndromes with Chromosome 3 Abnormalities" @default.
- W4238079255 doi "https://doi.org/10.1182/blood.v126.23.1705.1705" @default.
- W4238079255 hasPublicationYear "2015" @default.
- W4238079255 type Work @default.
- W4238079255 citedByCount "0" @default.
- W4238079255 crossrefType "journal-article" @default.
- W4238079255 hasAuthorship W4238079255A5010075752 @default.
- W4238079255 hasAuthorship W4238079255A5012863731 @default.
- W4238079255 hasAuthorship W4238079255A5013240910 @default.
- W4238079255 hasAuthorship W4238079255A5020819343 @default.
- W4238079255 hasAuthorship W4238079255A5026865748 @default.
- W4238079255 hasAuthorship W4238079255A5029369362 @default.
- W4238079255 hasAuthorship W4238079255A5035609080 @default.
- W4238079255 hasAuthorship W4238079255A5038107984 @default.
- W4238079255 hasAuthorship W4238079255A5041443589 @default.
- W4238079255 hasAuthorship W4238079255A5041754278 @default.
- W4238079255 hasAuthorship W4238079255A5049385583 @default.
- W4238079255 hasAuthorship W4238079255A5055740968 @default.
- W4238079255 hasAuthorship W4238079255A5061026876 @default.
- W4238079255 hasAuthorship W4238079255A5065722106 @default.
- W4238079255 hasAuthorship W4238079255A5066001318 @default.
- W4238079255 hasAuthorship W4238079255A5085974329 @default.
- W4238079255 hasAuthorship W4238079255A5090435894 @default.
- W4238079255 hasAuthorship W4238079255A5090527595 @default.
- W4238079255 hasConcept C104317684 @default.
- W4238079255 hasConcept C126322002 @default.
- W4238079255 hasConcept C143998085 @default.
- W4238079255 hasConcept C150194340 @default.
- W4238079255 hasConcept C190727270 @default.
- W4238079255 hasConcept C2776012956 @default.
- W4238079255 hasConcept C2780007613 @default.
- W4238079255 hasConcept C2780189214 @default.
- W4238079255 hasConcept C2780235182 @default.
- W4238079255 hasConcept C2780240888 @default.
- W4238079255 hasConcept C2780817109 @default.
- W4238079255 hasConcept C30481170 @default.
- W4238079255 hasConcept C53226629 @default.
- W4238079255 hasConcept C54355233 @default.
- W4238079255 hasConcept C71924100 @default.
- W4238079255 hasConcept C86803240 @default.
- W4238079255 hasConceptScore W4238079255C104317684 @default.
- W4238079255 hasConceptScore W4238079255C126322002 @default.
- W4238079255 hasConceptScore W4238079255C143998085 @default.
- W4238079255 hasConceptScore W4238079255C150194340 @default.
- W4238079255 hasConceptScore W4238079255C190727270 @default.
- W4238079255 hasConceptScore W4238079255C2776012956 @default.
- W4238079255 hasConceptScore W4238079255C2780007613 @default.
- W4238079255 hasConceptScore W4238079255C2780189214 @default.
- W4238079255 hasConceptScore W4238079255C2780235182 @default.
- W4238079255 hasConceptScore W4238079255C2780240888 @default.
- W4238079255 hasConceptScore W4238079255C2780817109 @default.
- W4238079255 hasConceptScore W4238079255C30481170 @default.
- W4238079255 hasConceptScore W4238079255C53226629 @default.
- W4238079255 hasConceptScore W4238079255C54355233 @default.
- W4238079255 hasConceptScore W4238079255C71924100 @default.
- W4238079255 hasConceptScore W4238079255C86803240 @default.
- W4238079255 hasIssue "23" @default.
- W4238079255 hasLocation W42380792551 @default.
- W4238079255 hasOpenAccess W4238079255 @default.
- W4238079255 hasPrimaryLocation W42380792551 @default.
- W4238079255 hasRelatedWork W10110336 @default.
- W4238079255 hasRelatedWork W1133061 @default.
- W4238079255 hasRelatedWork W12916179 @default.
- W4238079255 hasRelatedWork W5027048 @default.
- W4238079255 hasRelatedWork W5342291 @default.
- W4238079255 hasRelatedWork W6398642 @default.
- W4238079255 hasRelatedWork W8604413 @default.
- W4238079255 hasRelatedWork W893036 @default.
- W4238079255 hasRelatedWork W9644449 @default.
- W4238079255 hasRelatedWork W17826350 @default.
- W4238079255 hasVolume "126" @default.
- W4238079255 isParatext "false" @default.
- W4238079255 isRetracted "false" @default.
- W4238079255 workType "article" @default.