排序方式: 共有10条查询结果,搜索用时 0 毫秒
1
1.
Nucleophosmin 1 (NPM1) mutations in chronic myelomonocytic leukemia and their prognostic relevance
下载免费PDF全文
![点击此处可从《American journal of hematology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
2.
Tucker Coston Prateek Pophali Rangit Vallapureddy Terra L. Lasho Christy M. Finke Rhett P. Ketterling Ryan Carr Moritz Binder Abhishek A. Mangaonkar Naseema Gangat Aref Al-Kali Mark Litzow Darci Zblewski Animesh Pardanani Ayalew Tefferi Mrinal M. Patnaik 《American journal of hematology》2019,94(7):767-779
Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA- 45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P = .01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P = .37). In conclusion, this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria and underscores the need for newer, rationally derived therapies. 相似文献
3.
Domenico Penna Terra L. Lasho Christy M. Finke Rangit R. Vallapureddy Curtis A. Hanson Rhett P. Ketterling Animesh Pardanani Naseema Gangat Ayalew Tefferi 《American journal of hematology》2019,94(3):286-290
In the last decade, several prognostic models for primary myelofibrosis (PMF) have been introduced and shown to be effective in predicting overall survival. The main objective for this study was to identify clinical and genetic markers of very long (20+ years) survival in PMF. A total of 1282 patients with PMF were considered (median age 65 years, range 19-92; 63% males); 26 (2%) patients (median age 51 years, range 28-71; 38% males) survived their disease for at least 20 years (long-lived patients) and 626 (49%) patients (median age 68 years, range 27-92; 66% males) died within 5 years of their diagnosis (short-lived patients). Multivariable logistic regression analysis identified 7 variables that were associated with survival beyond 20 years: age ≤ 70 years (P = .002); female sex (P = .03); hemoglobin level ≥ 10 g/dL for women and ≥ 11 g/dL for men (P = .03), leukocyte count ≤25 × 109/L (P = .009), platelet count ≥100 × 109/L (P = .002), circulating blasts <2% (P = .03) and absence of constitutional symptoms (P = .04). Five-year mortality was independently predicted by high-molecular risk mutations (P < .001); unfavorable or very high risk karyotype (P < .001); absence of type 1/like CALR mutation (P < .001); age > 70 years (P < .001); constitutional symptoms (P < .001); hemoglobin level < 10 g/dL for women and < 11 g/dL for men (P < .001); leukocyte count >25 × 109/L (P = .004); and circulating blasts ≥2% (P = .001). This study suggests that genetic risk factors in PMF are associated with early mortality while survival beyond 20 years could be predicted by easily accessible clinical variables, including age, sex, blood counts, and symptoms. 相似文献
4.
5.
6.
Natasha Szuber Mythri Mudireddy Maura Nicolosi Domenico Penna Rangit R. Vallapureddy Terra L. Lasho Christy Finke Kebede H. Begna Michelle A. Elliott C. Christopher Hook Alexandra P. Wolanskyj Mrinal M. Patnaik Curtis A. Hanson Rhett P. Ketterling Shireen Sirhan Animesh Pardanani Naseema Gangat Lambert Busque Ayalew Tefferi 《Mayo Clinic proceedings. Mayo Clinic》2019,94(4):599-610
Objective
To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates.Patients and Methods
All Mayo Clinic patients with World Health Organization–defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).Results
A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF. From October 27, 1967, through December 29, 2017, 1631 deaths (54%), 183 leukemic transformations (6%), 244 fibrotic progressions (14%), and 516 thrombotic events (17%) were recorded. Median overall survival (OS) was 18 years for ET, 15 years for PV, and 4.4 years for PMF (P<.05 for all intergroup comparisons). Inferior survival was documented in patients with ET diagnosed more recently (post-1990) (P<.001), whereas survival data were time independent in PV and PMF. After conventional risk stratification, OS in low-risk ET and low-risk PV were superimposed (P=.89) but each differed significantly from that of age- and sex-matched controls (P<.001). Leukemia-free survival was similar for ET and PV (P=.22) and significantly worse with PMF (P<.001). Compared with ET, PV was associated with higher risk of fibrotic progression (P<.001). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (P=.002 for PV vs ET; P=.56 for ET vs PMF; and P=.001 for PV vs PMF).Conclusion
This study provides the most mature survival and outcomes data in MPNs and highlights MPN subgroup risk categorization as key in appraising disease natural history. The OS was only marginally better in ET compared with PV, and PV displayed a higher risk of thrombosis and fibrotic progression. 相似文献7.
Niraj Shenoy Mythri Mudireddy Rangit Vallapureddy Nelson Leung Lance Pagliaro Thomas Witzig Fang-Shu Ou Tamas Ordog John Cheville Mrinal Patnaik R. Houston Thompson Ayalew Tefferi Kebede Begna 《Clinical genitourinary cancer》2018,16(6):e1117-e1122
Background
Renal cell carcinoma (RCC) and certain myeloid malignancies are both characterized by widespread aberrant DNA hypermethylation. After clinical observations of patients with a personal history of both malignancies, we sought to explore a potential association, and to describe the clinical characteristics of these patients.Patients and Methods
Mayo Clinic's ‘Advanced Cohort Explorer’ database was used to identify patients with a history of both malignancies. Clinical features and long-term outcome were abstracted. Prevalence of myelodysplastic syndromes (MDSs) in patients ≥ 65 years with a personal history of nephrectomy for RCC was then compared with the prevalence of MDSs in the Dusseldorf MDS registry and the general patient population at Mayo Clinic, using 1-sample test of proportions.Results
A total of 59 patients with a diagnosis of both RCC and myeloid malignancy were identified. The myeloid malignancies included 38 MDSs, 12 acute myelogenous leukemia, and 9 myeloproliferative neoplasms. The cohort was characterized by marked male predominance (4.4:1). The median age at RCC diagnosis was 64 years (range, 37-87 years), and for myeloid malignancy was 75 years (range, 44-90 years). Prevalence of MDS in patients > 65 years with a personal history of nephrectomy for RCC was ≈ 8.4 times that of the age-concordant general population based on the Dusseldorf registry (28/6490 or 395/100,000 vs. ≈ 47/100,000; P < .001), and 3.07 times that of the age-concordant patient population at Mayo Clinic (28/6490 or 395/100,000 vs. 128.4/100,000; P < .001).Conclusions
We observed a strong association between RCC and MDS. Patients with a history of RCC appear to have a substantially increased risk of developing MDS compared with the general population. 相似文献8.
Khan AM Hundal R Ramaswamy V Korsten M Dhuper S 《World journal of gastroenterology : WJG》2004,10(16):2457-2458
Acute esophageal necrosis (AEN) or “black esophagus“ is a clinical condition found at endoscopy. It is a rare entity the exact etiology of which remains unknown. We describe a case of ‘black esophagus‘, first of its kind, in the setting of liver cirrhosis and hepatic encephalopathy. 相似文献
9.
Therapy related‐chronic myelomonocytic leukemia (CMML): Molecular,cytogenetic, and clinical distinctions from de novo CMML
下载免费PDF全文
![点击此处可从《American journal of hematology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Mrinal M. Patnaik Rangit Vallapureddy Fevzi F. Yalniz Curtis A. Hanson Rhett P. Ketterling Terra L. Lasho Christy Finke Aref Al‐Kali Naseema Gangat Ayalew Tefferi 《American journal of hematology》2018,93(1):65-73
Therapy related myeloid neoplasms (t‐MN) including therapy related myelodysplastic syndromes (t‐MDS) and acute myeloid leukemia (t‐AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t‐CMML. T‐CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t‐CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t‐MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t‐CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t‐CMML in comparison to d‐CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t‐CMML independently and adversely impacted OS (P = .0001 HR 2.1 95% CI 1.4‐3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P = .001, HR 2.4, 95% CI 1.5‐3.7) and the GFM prognostic model (P < .0001, HR 2.15, 95% CI 1.5‐3.7). In summary, we highlight the unique genetics and independent prognostic impact of t‐CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t‐MN. 相似文献
10.
Ayalew Tefferi Natasha Szuber Rangit R. Vallapureddy Kebede H. Begna Mrinal M. Patnaik Michelle A. Elliott C. Christopher Hook Alexandra P. Wolanskyj Curtis A. Hanson Rhett P. Ketterling Animesh Pardanani Naseema Gangat 《American journal of hematology》2019,94(1):5-9
First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1-1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study. 相似文献
1