MDS subclassification-do we still have to count blasts?
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ABSTRACT:
SUBMITTER: Huber S
PROVIDER: S-EPMC10079547 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
MDS subclassification-do we still have to count blasts?
Huber Sandra S Haferlach Torsten T Müller Heiko H Meggendorfer Manja M Hutter Stephan S Hoermann Gregor G Baer Constance C Kern Wolfgang W Haferlach Claudia C
Leukemia 20230222 4
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Project description:Hypomethylating treatment (HMT) has been suggested as a feasible bridge to hematopoietic stem cell transplantation (HSCT), but controversies exist around influences of HMT response on transplant outcomes. To assess the safety and influences of pre-transplant HMT focusing on debulking effects and transplant outcomes, we retrospectively analyzed consecutive HSCT-eligible patients who received HMT for higher-risk MDS with excess blasts. Of all 98 patients, 11 patients failed to proceed to HSCT and HMT-related mortality occurred in 8 patients. When excluding 9 patients who refused HSCT, 87% of scheduled HSCT (77 of 89) was performed after a median of 3 cycles (range, 1-8) of HMT. The 4-year overall survival after HMT (n = 98) and HSCT (n = 77) was 44.0% and 53.6%, respectively. Transplant outcomes were significantly different by the final response at HSCT; marrow response group (complete remission, marrow complete remission with or without hematologic improvement) showed significantly better 4-year disease-free survival compared to no marrow response group (n = 36, 87.3% vs. n = 41, 10.7%, P < 0.001). This difference between the groups was also evident in overall survival (90.9% vs. 8.6%, P < 0.001) and cumulative incidences of relapse (6.5% vs. 45.4%, P < 0.001) and treatment-related mortality (6.2% vs. 43.9%, P < 0.001). These observations indicate that pre-transplant HMT is a feasible bridging treatment in patients with excess blasts regarding high success rate of proceeding to transplantation and good survival rate. Marrow response at HSCT regardless of concomitant hematological improvement is an independent predictor of better survival, suggesting that immediate HSCT rather than continuing HMT should be performed once marrow response is achieved.
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Project description:Recently, MDS with mutated SF3B1 and blast count <5% was proposed as distinct entity with favorable prognosis by the international working group for the prognosis of MDS (IWG-PM), the 5th edition of the WHO classification and the International Consensus Classification. To further characterize this entity with respect to the genomic landscape, AML transformation rate and clinical outcome, we analyzed 734 MDS patients by whole genome sequencing. SF3B1 mutations were identified in 31% (n = 231), most frequently accompanied by TET2 mutations (29%). 144/231 (62%) SF3B1mut samples fulfilled entity criteria proposed by IWG-PM (SF3B1ent). These cases were associated with longer survival, lower AML transformation rate, normal karyotypes and harbored less accompanying mutations compared to SF3B1mut samples not falling into the proposed SF3B1 entity (SF3B1nent). Of SF3B1mut cases 7% (15/231; SF3B1ent: 3/144 [2%]; SF3B1nent: 12/87 [14%]) progressed to AML compared to 15% SF3B1 wild-type patients (75/503). Of these 15 SF3B1mut cases, 10 (67%) showed RUNX1 mutations at MDS or AML stage. Multivariate analysis revealed that del(5q) and RUNX1 mutations were independent negative prognostic factors for overall survival, while blast count >5% was not. In conclusion, SF3B1mut MDS has a favorable prognosis independent of blast count if karyotype and RUNX1 mutations are considered.
| S-EPMC9712089 | biostudies-literature
Project description:Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.
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Project description:To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis, we performed gene expression of lung adenocarcinoma profiling by cDNA microarray.
2011-07-19 | GSE20853 | GEO
Project description:Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and validated by non-negative matrix factorization . BACKGROUND: Current clinical and histopathological criteria used to define lung squamous cell carcinomas (SCCs) are insufficient to predict clinical outcome. We attempted to make a clinically-useful classification based on gene expression profiling. METHODS: We used cDNA microarrays with 40386 elements to analyze the gene expression profiles of 48 surgically resected samples of lung SCC. 9 samples of lung adenocarcinoma and 30 of normal lung were also included to give a total of 87 samples analyzed. After gene filtering, the data were subjected to hierarchical clustering and consensus clustering with the non-negative matrix factorization (NMF) approach. FINDINGS: Initial analysis by hierarchical clustering allowed division of SCCs into two distinct subclasses. An additional independent round of hierarchical clustering and consensus clustering with the NMF approach provided a validation for the classification. Kaplan-Meier analysis with the log rank test pointed to a non-significant difference in survival (p=0.071) but the likelihood of survival to 6 years was significantly different between the two groups (40.5% vs 81.8%, p=0.014, Z-test). Biological process categories characteristic for each subclass were identified statistically and up-regulation of cell-proliferation related genes was evident in the subclass with a poor prognosis. In the subclass with the better survival, genes involved in differentiated intracellular functions, such as the MAPKKK cascade, ceramide metabolism, or regulation of transcription, were up-regulated. Keywords: repeat sample
2009-04-01 | GSE2088 | GEO
Project description:To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis, we performed gene expression of lung adenocarcinoma profiling by cDNA microarray. adenocarcinoma 154, squamous 10
2011-07-18 | E-GEOD-20853 | biostudies-arrayexpress
Project description:The proliferation marker Ki-67 is widely used within the field of diagnostic histopathology as a prognostic marker for solid cancers. However, Ki-67 is hardly used for prognostic and diagnostic purposes in flow cytometric analyses of hematologic neoplasms. In the present study, we investigated to what extent the proliferative activity, as determined by Ki-67 expression, is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Bone marrow aspirates from 74 patients suffering from MPN, MDS, or MDS/MPN, and aspirates from 50 non-malignant cases were analyzed by flow cytometry for Ki-67 expression in the erythro-, myelo-, and monopoiesis. Ki-67 expression was used to investigate the proliferative activity during the various maturation steps within these hematopoietic cell lineages. In the MPN patient cohort, the proliferative activity of all cell lineages is significantly higher during almost all maturation stages compared to those of the benign control cohort. In the MDS and MDS/MPN cohort, a significantly lower proliferative activity is observed in the early maturation stages. In the MDS/MPN patient cohort, increased proliferative activity is seen in the later stages of the maturation. MDS and MDS/MPN display a distinct pattern in the proliferating fraction of maturing hematopoietic cells. This could become of added value in order to classify these malignancies based on their biological background and behavior, as well as in gaining a better understanding into the pathobiology of these malignancies.
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Project description:To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis, we performed gene expression of lung adenocarcinoma profiling by cDNA microarray. adenocarcinoma 154, squamous 10
| S-ECPF-GEOD-20853 | biostudies-other
Project description:Etiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCC) respond well to chemoradiotherapy, for undetermined reasons, a subgroup of patients experience a poor outcome. Despite cumulative efforts for discovering independent predictors for overall survival, both nodal status and tumor size are still the only reliable factors predicting patient outcome. In the present study, we correlated both proteomic signatures and clinicopathological features of neoplastic lesions arising from two distinct portions of the anal canal: the lower part (squamous zone) and the more proximal anal transitional zone. Although microdissected cancer cells appeared indistinguishable by morphology (squamous phenotype), unsupervised clustering analysis of the whole proteome significantly highlighted the heterogeneity that exists within anal canal tumors. More importantly, two region-specific subtypes of SCC were revealed. The expression profile (sensitivity/specificity) of several selected biomarkers (keratin filaments) further confirmed the subclassification of anal (pre)cancers based on their cellular origin. Less commonly detected compared to their counterparts located in the squamous mucosa, SCC originating in the transitional zone displayed more frequently a poor or basaloid differentiation and were significantly correlated with reduced disease-free and overall survivals. Taken together, we present for the first time direct evidence that anal canal SCC comprises two distinct entities with different cells of origin, proteomic signatures and survival rates. This study forms the basis for a novel dualistic classification of anal carcinoma with implications for management, outcome expectations and possibly therapeutic approaches.
2016-12-20 | PXD004859 | Pride