BACKGROUND Sinonasal natural killer (NK)/T‐cell or T‐cell lymphoma behaves quite differently from other lymphomas. The objective of this study was to investigate clinical features, treatment outcomes, and failure patterns in patients with this type of sinonasal lymphoma. METHODS From September, 1977 to December, 2000, 77 patients with sinonasal NK/T‐cell lymphoma or T‐cell lymphoma who had received radiotherapy (R/T), chemotherapy (C/T), or both (R/T and C/T) were evaluated retrospectively. RESULTS Fifty‐six patients (73%) had locoregional disease only, and 21 patients (27%) had systemic involvement. Forty‐four patients (57%) achieved a complete remission (CR). The 5‐year overall survival rate was 36% (median follow‐up, 89 months). Achievement of CR was the only prognostic factor for survival in multivariate analysis. Among patients with locoregional disease, the CR rate was 63%, and the 5‐year overall survival rate was 42%. Combined R/T and C/T or R/T alone resulted in better survival compared with C/T alone (5‐year survival rates, 59%, 50%, and 15%, respectively; P = 0.01). Incidences of locoregional and systemic failure were 43% and 30%, respectively. Outcome was dismal for patients with systemic disease, with a CR rate of 43% and a 5‐year survival rate of 25%. Only 2 of 21 patients had sustained remissions. The locoregional and systemic failure rates were 57% and 71%, respectively. CONCLUSIONS Treatment outcomes were unsatisfactory for patients with locoregional and systemic sinonasal NK/T‐cell or T‐cell lymphoma. R/T could not control locoregional disease satisfactorily, and C/T was unable to eradicate systemic disease in many patients. High‐dose therapy may be worth studying in these patients. New treatments should be investigated to increase remission rates, prevent failure, and improve survival. Cancer 2004;100:366–75. © 2003 American Cancer Society.
Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate-risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SFmutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML.
Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.
Hyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo-HSCT in first CR seems to ameliorate the poor prognostic impact of HL.
BackgroundMulticolor flow cytometry (MFC) analysis is widely used to identify minimal residual disease (MRD) after treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, current manual interpretation suffers from drawbacks of time consuming and interpreter idiosyncrasy. Artificial intelligence (AI), with the expertise in assisting repetitive or complex analysis, represents a potential solution for these drawbacks.MethodsFrom 2009 to 2016, 5333 MFC data from 1742 AML or MDS patients were collected. The 287 MFC data at post-induction were selected as the outcome set for clinical outcome validation. The rest were 4:1 randomized into the training set (n = 4039) and the validation set (n = 1007). AI algorithm learned a multi-dimensional MFC phenotype from the training set and input it to support vector machine (SVM) classifier after Gaussian mixture model (GMM) modeling, and the performance was evaluated in The validation set.FindingsPromising accuracies (84·6% to 92·4%) and AUCs (0·921–0·950) were achieved by the developed algorithms. Interestingly, the algorithm from even one testing tube achieved similar performance. The clinical significance was validated in the outcome set, and normal MFC interpreted by the AI predicted better progression-free survival (10·9 vs 4·9 months, p < 0·0001) and overall survival (13·6 vs 6·5 months, p < 0·0001) for AML.InterpretationThrough large-scaled clinical validation, we showed that AI algorithms can produce efficient and clinically-relevant MFC analysis. This approach also possesses a great advantage of the ability to integrate other clinical tests.FundThis work was supported by the Ministry of Science and Technology (107-2634-F-007-006 and 103–2314-B-002-185-MY2) of Taiwan.
Background Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3 , a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS. Methods shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance . Results Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P < 0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group. Conclusions This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group. Electronic supplementary material The online version of this article (10.1186/s12885-019-5822-y) contains supplementary material, which is available to authorized users.
Acute myeloid leukemia (AML) with double mutant CCAAT/enhancer binding protein α (CEBPA dm ) is a new entity in the 2016 World Health Organization (WHO) classification with unique biologic features and prognostic implications. 1,2 The incidence of CEBPA dm ranges from 7.5% to 11% in AML. 1,3,4 CEBPA dm AML patients, when treated with standard chemotherapy, achieve a high complete remission (CR) rate. However, relapse occurs in 40% of patients who attain CR. 1 This has raised the clinically relevant question whether concomitant genetic alterations influence the prognosis of CEBPA dm patients. Apart from GATA2, the prognostic impact of other concomitant gene mutations is largely unsettled because limited patient numbers preclude informative analyses. 5 Given that AML is a heterogeneous disease, risk-adapted treatment may not only improve the prognosis, but also reduce toxicity from the therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first CR is not beneficial for cytogenetically normal AML (CN-AML) patients with CEBPA dm . 6 If any concomitant mutations adversely affect the clinical outcome of CEBPA dm patients, it will be interesting to know whether allo-HSCT should be performed for these patients. As yet, there is no data to answer this question.In this study, the aim was to identify additional mutations in CEBPA dm AML patients that conferred prognostic significance. Furthermore, we investigated the role of allo-HSCT in CEBPA dm patients with concurrent adverserisk mutations. Mutation analyses in CEBPA and 19 other relevant genes, including FLT3-ITD, FLT3-
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