scholarly journals Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of Who 2001 Versus Who 2008/2016 Criteria in a Large Single Center Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5464-5464
Author(s):  
Sofia Chiatamone Ricci ◽  
Maria Antonietta Arleo ◽  
Stefania Trasarti ◽  
Cristina Santoro ◽  
Massimo Breccia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Features ◽  
Essential Thrombocythemia ◽  
Advisory Board ◽  
World Health ◽  
Thrombotic Risk ◽  
Entire Cohort ◽  
Prognostic Features ◽  
Who 2008

Abstract According to the World Health Organization (WHO) 2008/2016 criteria for classification of myeloid neoplasms, a platelet (PLT) count ≥ 450X109/l, thus reduced from the previous WHO 2001 level ≥ 600 x 109/l, was considered the new PLT threshold for the diagnosis of Essential Thrombocythemia (ET). Aim of the study was to validate in a setting of current clinical practice this important diagnostic change and compare clinical and hematological features at diagnosis and during follow-up of patients with PLT ≥600 x 109/l versus patients with PLT < 600 x 109/l. We retrospectively analyzed data from 264 patients with ET according to WHO 2008/2016 criteria, enrolled in our center from 1/2008 to 12/2017. Patients were divided into Group A (G-A) (PLT ≥600 x 109/l at diagnosis) (199 patients - 75.4%) and Group B (G-B) (PLT ≥ 450 x 109/l < 600 x 109/l at diagnosis) (65 patients - 24.6%) and compared for clinical features at the onset, clinical course and follow-up. Main features and commonly recognized pro-thrombotic risk factors at diagnosis of the entire cohort as well as of G-A and G-B are reported in the Table 1. Among clinical features, only the median value of leukocytes was significantly higher in G- A [9.1 x 109/l, interquartile range (IQR) 7.8-10.3 vs 7.4 x 109/l, IQR 6.0-9.6; p = 0.001]. Among pro-thrombotic risk factors, only the median cholesterol value was significantly lower in the G-A [187 mg/dl (IQR 164-220) vs 204 mg/dl (RIQ 177-238); p = 0.048]. Cytostatic treatment was administered in 175 patients (71.1%) of entire cohort at different intervals from diagnosis, with a significantly higher rate in patients of G-A (76.9% versus 49.2%, p <0.001). After a median follow-up of 37.5 months (IQR 19.8 - 60.7), 13 thrombotic events (4.9%) were recorded in the entire cohort (7 episodes in the G-A and 6 episodes in the G-B), with a 5-year Cumulative Incidence of Thrombosis (CIT) significantly higher in the G-B [79.6% (95%CI 59.6 - 99.6) versus 95.4% (95%CI 91.8 - 99.0); p=0.047] (Figure 1). No patient evolved in myelofibrotic phase, 2 patients evolved in blastic phase (BP) after 42 and 58 months, respectively [1 patient (0.5%) in the G-A and 1 patient (1.3%) in the G-B; p=0.40). At the last follow-up, 4 patients (1.5%) died (1 from BP, 1 from cerebral hemorrhage, 2 from unavailable cause), 15 (5.7%) were lost to follow-up and 245 (92.8%) are still alive and currently followed at our Institute. The 5-year Overall Survival (OS) of the entire cohort was 96.2% (IC95% 92.2 - 100), without differences between the two groups [96.3% (95% CI 92.0 - 100) in the G-A versus 96.7% (IC95% 91.7 - 100) in the G-B; p=0.898]. Our data indicate a substantial homogeneity among ET patients regardless of the PLT number at diagnosis, thus confirming the usefulness of 2008/2016 WHO diagnostic criteria. Furthermore, the counterintuitive lower CIT observed in G-A, due to a larger use of cytostatic treatments and/or to an acquired Von Willebrand phenomenon when PLT levels > 1.000 x 109/l, highlights how thrombotic risk is unrelated to PLT value and leads to consider the administration of adequate cytostatic therapy even in patients with relatively lower PLT count at diagnosis. Disclosures Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Foà:INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau.

Cerebral infarcts associated with migraine: Clinical features, risk factors and follow-up

1996 ◽  
Vol 243 (7) ◽  
pp. 511-515 ◽  
Author(s):  
R. A. H. Hoekstra-van Dalen ◽  
J. P. M. Cillessen ◽  
L. J. Kappelle ◽  
J. Gijn
Keyword(s):  
Risk Factors ◽  
Clinical Features ◽  
Cerebral Infarcts

Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Samantha Ferrari ◽  
Chiara Pagani ◽  
Mariella D'Adda ◽  
Nicola Bianchetti ◽  
Annamaria Pelizzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Advisory Board ◽  
Advisory Committees ◽  
Risk Status ◽  
History Of ◽  
Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=&lt;0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Essential Thrombocythemia: Analysis of Risk Factors for Thrombotic Events in a Series of 306 Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4937-4937
Author(s):  
Franca Radaelli ◽  
Stefania Bramanti ◽  
Mariangela Colombi ◽  
Alessandra Iurlo ◽  
Alberto Zanella
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Essential Thrombocythemia ◽  
Thrombotic Event ◽  
Previous History ◽  
Significant Difference ◽  
Platelet Number ◽  
History Of

Abstract Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by peripheral thrombocytosis and abnormal proliferation of megakariocytes in the bone marrow. Even thought thrombosis is frequently associated to ET, the risk factors of this clinical complication are still controversial. The aim of this retrospective, single institution study was to investigate clinical and laboratory characteristics associated with the occurrence of thrombotic events, with the purpose of identifying subgroups of patients who could benefit from antiaggregant and/or cytostatic treatment. 306 consecutive ET patients (109 men and 197 females, median age 58 yr) diagnosed between January 1979 and December 2002 were included in the study. At the time of analysis, 196 patients were still alive with a median follow up of 96 months. The following variables were investigated for the association with thrombotic complications: age, platelet count, previous history of thrombotic events, time from diagnosis, treatment with antiaggregant/cytostatic drugs, and cardiovascular risk factors such as arterial hypertension, obesity, hypercolesterolemia, diabetes, cigarette smoking. At the time of last follow up, 46 patients (15%) experienced at least one thrombotic event. The occurrence of thrombotic events was observed in 26/64 (40.6%) patients with previous history of thrombosis and in 20/242 (8.3%) patients with no previous history of thrombosis (p&lt;0.0001 Fisher’s exact test, odd ratio 7.6). A significant difference between the two groups of patients was also confirmed when Kaplan Meier estimates of thrombosis-free survival were compared by log-rank test (p&lt;0.0001). By logistic regression, platelet number at diagnosis did not associate with occurrence of thrombosis in the whole patient population. When patients without previous history of thrombosis were stratified according to the number of cardiovascular risk factors (none vs one vs more than one), a significant correlation with occurrence of thrombotic events was observed (Mantel-Haenszel Chi-square 5.47, p&lt;0.05). This study confirms that history of thrombosis is strongly related with risk of further thrombotic events in patients with ET, whereas platelet number at diagnosis does not seem to represent a prognostic factor. In patients with no previous history of thrombosis, the presence of other cardiovascular risk factors has to be taken into account when establishing the therapeutic approach.

Cytoreductive Therapeutic Approach in the Essential Thrombocythemia (ET) Patients of the Registro Italiano Trombocitemia (RIT): Preliminary Data

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5248-5248
Author(s):  
Luigi Gugliotta ◽  
Alessia Tieghi ◽  
Anna Candoni ◽  
Monia Lunghi ◽  
Gianluca Gaidano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Essential Thrombocythemia ◽  
Therapeutic Approach ◽  
Jak2 V617f ◽  
Bone Marrow Biopsies ◽  
Thrombotic Risk ◽  
Significant Difference ◽  
Cytoreductive Treatment ◽  
Wbc Count

Abstract Background: the Registro Italiano Trombocitemia, that is a GIMEMA project, has been activated to registry Italian Essential Thrombocythemia (ET) patients, to improve the diagnosis appropriateness (WHO criteria), to verify the prognostic value of the clinical and biological parameters, to evaluate the compliance to the therapeutical Italian guidelines (1), and to create a network for activation of new studies. Objective: this analysis is mainly devoted to describe the ET patients registered in the RIT and to evaluate the therapeutic approach adopted in the 102 participating hematological centers. Material and methods: two thousand and fifteen ET patients have been registered after the written informed consent was obtained, and data validation by various expert panels is in progress. This preliminary report considers 1785 patients, diagnosed mainly (1078, 60.4%) since the publication in the year 2004 of the ET therapy Italian guidelines (1). Results: the patients, 678 (38%) males and 1107 (62%) females, showed at diagnosis: age 60.3 ± 16.8 years with higher values in males than in females (61.7 ± 15.3 vs. 59.4 ± 17.7, p&lt;0.05), being the patients below 40 years 14% and those over 70 years 33% of cases; PLT count (109/L) 846 ± 309 with lower values in males than in females (813 ± 261 vs. 866 ± 334, p&lt;0.002), and with values 1001–1500 and over 1500 in 16% and 4% of cases, respectively; WBC count (109/L) 9.1 ± 2.9, without difference by sex, and with values 12–15 in 10% and over 15 in 3% of cases; Hgb (g/dL) 14.2 ± 1.6 with higher values in males than in females (14.8 ± 1.5 vs. 13.8 ± 1.5, p&lt;0.001), and with values over 16.5 in 8.5% of males and 2.7% of females, respectively; splenomegaly in 488 (27%), echo-documented in 324 cases (18%); history of hemorrhage and thrombosis in 90 (5%) and 325 (19%) of cases, respectively; disease-related symptoms in 41% and general thrombotic risk factors in 93% of cases, respectively. The WHO 2001 diagnostic criteria were reported for 33% of cases observed before the year 2004 and for 53 % of cases observed since the year 2004. Detailed data at diagnosis were reported as follows: bone marrow biopsy in 1087 cases (61%) with a frequency of 51% and 68% before and since the year 2004, respectively; bcr-abl study in 1045 cases (59%); cytogenetics in 828 cases (46%) with karyotype abnormalities in 27 patients (3%). The JAK2 V617F mutation, searched in 574 cases (32%), was observed in 320 of them (56%). The patient follow-up was 4.5 ± 4.5 years with a total of 5245 pt-yrs. During the follow-up the hemorrhagic events were 5.7% (1.3/100 pt-yrs), being the major events 1.9% (0.4/100 pt-yrs); the thrombotic complications were 14.9 % (3.3/100 pt-yrs), resulting the major arterial 9.4% (2.1/100 pt-yrs), the major venous 3.5% (0.8/100 pt-yrs) and the minor thrombosis 2% (0.4/100 pt-yrs). An antiplatelet treatment, almost always with low dose aspirin, was performed in 75% of the patients, without significant difference in the cases diagnosed before and since the 2004. A cytoreductive treatment was done with use of Hydroxyurea (HU, 64%), Interferon alpha (IFN, 16%), Anagrelide (ANA, 15%), Busulfan (BUS, 4%), and Pipobroman (PIPO, 2 %). In the ET patients diagnosed since the year 2004 respect those diagnosed before, it was observed a decrease in the use of all the cytoreductive drugs, particularly BUS (−62%), IFN ((−62%), and ANA ((−68%). The use of the cytoreductive drugs was related to the patient mean age (years): BUS (76), PIPO (72), HU (67), ANA (53), IFN (48). In the patients diagnosed since the 2004 as compared with those before 2004, the mean age of the treated patients increased for BUS (from 69 to 81 yrs, p&lt;0.001) and for HU (from 64 to 69 yrs, p&lt;0.001) while it decreased for IFN (from 49 to 46 yrs, p&lt;0.05). Conclusion: in the analyzed patients of the ET Italian registry the diagnosis appropriateness resulted improved in the cases observed since the year 2004 respect those observed before, with an increase of bone marrow biopsies from 51% to 68% of patients. Moreover, in accord with the ET therapy Italian guidelines, the use of the cytoreductive drugs was less frequent in the patients diagnosed since the year 2004 than before (particularly for BUS, IFN, and ANA) and the more safe molecules IFN and ANA were preferentially deserved to the younger patients.

Risk Factors for Thrombosis Vary According to Age in Patients with Essential Thrombocythemia: a Retrospective Analysis of 1090 Patients from the “Gruppo Laziale SMPC Ph Negative “,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3854-3854
Author(s):  
Marco Montanaro ◽  
Roberto Latagliata ◽  
Michele Cedrone ◽  
Nicoletta Villivà ◽  
Raffaele Porrini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Thrombotic Event ◽  
Age Groups ◽  
Thrombotic Risk ◽  
Mutational Status ◽  
Group A ◽  
Group B

Abstract Abstract 3854 Increasing age is a well-recognised risk factor for thrombotic events in patients with Essential Thrombocythemia (ET): however, few data exist on the role of other clinical and biological features in different age groups. To address this issue, we analysed retrospectively 1090 ET patients (M/F 403/687, median age 63 years, IR 17 – 96) diagnosed at 11 Hematological Institutions in the Lazio region from 1980 to 2010 and with a median period of follow-up of 84 months (IR 1 – 371). Based on the commonly adopted age threshold, 480 patients (44 %) were < 60 years (Group A) and 610 (56 %) were ≥ 60 years (Group B). Clinical and biological features as well as cardiovascular risk factors analyzed for the impact on the thrombotic risk in the two age groups are reported in the Table.Group A < 60 yearsGroup B ≥ 60 yearsPutative risk factorsRisk ratio (95% CI)P valueRisk ratio (95% CI)P valueM/F167/3132.68 (1.03–6.94)0.0029236/3741.12 (0.17–2.59)0.73WBC median (range) x 109/l8.9 (4.29–22.35)0.387 (0.149–1,004)0.06458.9 (1.2–57.7)0.79 (0.41–1.47)0.445PLTS median (range) x 109/l837 (451–3582)0.37 (0.258–1.70)0.66802 (450–3104)0.52 (0.28–0.99)0.0052Hb median, g/dL (range)14.1 (6.0–18.4)0.86 (0.33–2.24)0.76914.0 (7.0–17.8)0.87 (0.45–1.67)0.674*JAK-2 mutational status: wild type/mutated (%)53.2/46.81.57 (0.50–4.87)0.4434.1/65.90.498 (0.17–1.48)0.209Previous thrombotic events: n° (%)· All events72 (15)2.18 (0.59–7.96)0.12149 (24.4)3.01 (1.38–6.57)0.0004· within 24 months from diagnosis48 (10)1.43 (0.19–10.4)0.7464 (10.5)0.506 (0.18–1.39)0.189· within 60 months from diagnosis60 (12.5)NA0.5191 (14.9)0.323 (0.11–0.95)0.023Cardiovascular risk factors: Y/N %○ Arterial hypertension41.7/58.31.68(0.64–4.36)0.2880.7/19.30.96 (0.36–2.57)0.935○ Diabetes10.2/89.81.11 (0.23–5.15)0.8925.0/75.01.09 (0.38–3.11)0.86○ Smoking attitude45.6/54.42.78 (1.01–7.65)0.06758.3/41.71.04 (0.35–3.09)0.94○ Hyperlipidemia31.0/69.03.11(0.917–10.592)0.03951.6/48.42.31 (0.70–7.55)0.203 In Group A, 39 patients (8.1%) had at least one thrombotic event during follow-up; there were 20 (51.3%) arterial thrombosis and 19 (48.7%) venous thrombosis. In Group B, 63 patients (10.3%) had at least one thrombotic event during follow-up; there were 38 (69.4%) arterial thromboses and 25 (39.6%) venous thromboses. In group A univariate analysis for thrombosis-free survival performed by Kaplan-Meier method, disclosed a significant impact of male gender (p=0.0029, CI 1.03–6.94, HR 2.68), > 2 cardiovascular risk factors (p=0.0002, CI 1.87 – 190, HR 18.94) and isolated hyperlipidemia (p=0.039, CI 0.917 – 10.59, HR 3.11), while previous thrombotic events had no significant impact (p=0.27). By contrast, the presence of a previous thrombotic event was the only feature with a significant impact on thrombotic risk in Group B (p=0.0004, CI 1.38 – 6.55, HR 3.01). WBC and PLTS values at different cut-off levels as well as JAK-2 mutational status did not have any impact on thrombosis in either age groups. However, in group B, we observed a trend (p=0.052, CI 0.28–0.99, HR 0.52) towards a protective effect of higher PLTS values (> 800 × 109/l). In conclusion, our data seem to reinforce the need of a different thrombotic risk assessment in distinct age groups: in particular, younger patients could benefit from early recognition and treatment of well-known cardiovascular risk factors. Disclosures: No relevant conflicts of interest to declare.

Short Survival and High Rates of Transformation Prevail in Chronic Myelomonocytic Leukemia Despite Hypomethylating Agent Therapy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2800-2800
Author(s):  
Emily J. Vannorsdall ◽  
Vu H. Duong ◽  
Xinyi Ng ◽  
Dan P. Zandberg ◽  
Michael L. Tidwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Research Funding ◽  
Response Rates ◽  
Chronic Myelomonocytic Leukemia ◽  
World Health ◽  
Free Survival ◽  
Entire Cohort ◽  
Myelomonocytic Leukemia

Abstract Abstract 2800 Background: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder categorized as a mixed myeloproliferative/myelodysplastic disorder in the World Health Organization classification system. Diagnostic criteria include a persistent peripheral blood monocytosis >1 × 109/L and bone marrow dysplasia. Our recent review of SEER Medicare data (ASH 2011 abstract 2784) demonstrated that CMML has a shorter overall survival (OS) and more frequent progression to acute myeloid leukemia (AML), compared to myelodysplastic syndromes (MDS). Due to the heterogeneity of this disease and its differences from MDS, efforts to identify prognostic factors have been ongoing. The MD Anderson prognostic score was previously validated, but was derived from patients treated prior to the availability of the hypomethylating agents (HMAs) azacitidine and decitabine. HMAs have now emerged as standard therapy, with reported response rates of 37–69%, but their impact on survival and AML transformation is unclear. The OS of CMML patients has been reported at 12–18 months and transformation rates have varied between 15–52%. We reviewed our own single-center experience with CMML over the past 12 years. Methods: We conducted a retrospective review of CMML patients evaluated at the University of Maryland Greenebaum Cancer Center between January 2000 and August 2012. Patient and disease characteristics, treatments, complications, progression to AML, and OS were recorded and analyzed. Descriptive statistics were used for baseline characteristics and Kaplan-Meier analysis was performed for all time-to-event data. Statistical analyses were performed using SPSS version 20.0. Results: We identified 35 patients with CMML, 71% were male and 71% white, with a median age of 69 (range 34–86) years; 75% had <10% bone marrow (BM) blasts and 68% had low-risk cytogenetic findings (normal karyotype or -Y). Most patients treated prior to 2005 received hydroxyurea and/or erythropoiesis-stimulating agents or were enrolled on clinical trials, while patients treated since 2005 received HMAs as primary therapy. The median OS of the entire cohort was 19.5 months, with 49% of patients progressing to AML with a median time to progression (TTP) of 16.9 months. Of the entire cohort, patients with <10% and ≥10% BM blasts had an estimated OS of 19.4 and 11.7 months respectively (p=.021). Patients with low-, intermediate-, and high-risk (complex karyotype, +8, or chromosome 7 abnormalities) cytogenetic findings had an estimated OS of 23.3, 16.5, and 12.0 months respectively (p<0.001). Twenty-two patients received HMAs. Their estimated OS was 16.5 months, compared to 23.0 months for patients who did not receive HMAs (p =.683); 50% of patients treated with HMAs had known progression to AML, with TTP varying from 3–28 months. AML-free-survival was 16 months in patients receiving HMAs, compared to 14 months in patients not treated with HMAs (p=0.960). The majority of patients receiving HMA therapy (63%) were treated with ≥ 6 cycles; 57% of these patients transformed to AML despite initial response, often in a sudden and unpredictable manner. Conclusions: Published trials using HMAs in CMML have been limited by small patient numbers, short median follow-up, and paucity of data on AML transformation. Our study had a median follow-up period of 41.1 months. We found a high rate of AML transformation and short OS even in patients who received HMAs. HMA treatment had no statistically significant impact on AML-free survival or OS. Although the results may be confounded by some selection bias, treatment with HMAs was largely based on the date of diagnosis rather than prognostic variables or performance status. Therefore, the favorable response rates previously reported with these agents, and also seen in our patients, do not appear to translate into an OS or AML-free-survival advantage. Our study underscores the continued need for novel agents and the need to prioritize clinical trials for this group of patients. Additionally, based on our data, early bone marrow transplantation should be strongly considered for CMML patients when feasible. Disclosures: Davidoff: Novartis: Research Funding; Celgene: Research Funding; GlaskoSmithKline: Research Funding. Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding.

Essential Thrombocythaemia in Young Adults: Clinical Characteristics and Outcomes – a Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5060-5060
Author(s):  
Grace Kam ◽  
Richard Yiu ◽  
Ai Leen Ang ◽  
Yvonne SM Loh ◽  
Yeh Ching Linn ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Disease Progression ◽  
Young Patients ◽  
Medical Attention ◽  
Thrombotic Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Thrombosis Rate

Abstract Abstract 5060 Less than 20% of patients with essential thrombocythemia (ET) are diagnosed below the age of 60. Patients with ET have increased risk of thrombosis and bleeding and potential for progression to myelofibrosis (MF) or acute myeloid leukaemia (AML). In limited studies of young patients, the clinical course has been relatively benign with low rates of transformation to AML or MF. Thrombohemorrhagic events are generally few, but higher than that of the general population. This study aims to characterize of a group ET patients diagnosed at age ≤40, their thrombotic and hemorrhagic events, disease progression and treatment given. Patients were identified through a single institution MPN registry. This is an IRB approved registry that captures comprehensive information about patients with ET. Data on patient demographics, treatment, and disease-related events were obtained. Patients were diagnosed from 1975–2011, using either WHO or PVSG criteria depending on date of diagnosis. Kaplan-Meier method was used for survival analysis. 59 patients were diagnosed with ET at age ≤40. Median age of diagnosis was 31. 5years (range 16–40), with a median follow up of 7. 7years (0. 4–33. 8). All were of Asian descent: 81. 4% Chinese, 11. 9% Malay, 3. 4% Indian and 3. 4% Filipino. 40. 7% were male. JAK2 V617F mutation was screened for in 61%. Of these patients, 11 were positive, 25 negative for the mutation. Mean presenting counts were: WBC 10. 7 × 109/L (5. 9–21. 3), Hb 13. 6g/dL (9. 7–16. 4), platelets 957 × 109/L (449–2377). Splenomegaly was noted in 3 patients. 20. 3% had underlying hypertension, 16. 9% hyperlipidemia and 5. 1% diabetes mellitus. One patient had a prior stroke. Another had prior portal vein thrombosis. At diagnosis, 23. 7% were symptomatic, with microvascular symptoms of headache (11. 9%) and giddiness (6. 8%) being most common. The remainder were diagnosed incidentally, on health screening or when seeking medical attention for unrelated conditions. One patient presented with a myocardial infarction at diagnosis, while another had a significant bleeding post hemorrhoidectomy with drop in Hb by >2g/dL (platelet 2457 × 109/L). Based on a history of prior thrombosis, 3 patients were defined as high risk for thrombotic events. 67. 8% of patients had cytoreduction, indications being platelets ≥1500 × 109/L (n=16), presence of risk factors for atherosclerotic disease (n=11) and history/onset of thrombosis (n=5). In 8, the reason for cytoreduction could not be ascertained. Hydroxyurea was most commonly used (62. 7%), followed by anagrelide in 52. 5% and interferon 25. 4%. 5. 1% received busulphan, and 1. 7% 32P. Use of antiplatelet therapy was noted in 83. 8%, most frequently aspirin (76. 5%) and ticlopidine (11. 9%). On follow up, 2 arterial thromboses occurred (stroke, TIA), giving a thrombosis rate of 0. 39%/patients/year. Neither was a recurrent thrombosis. No venous thrombosis or major bleeds occurred. 20. 4% had minor mucocutaneous bleeding; 5 had platelets ≥1500 × 109/L at that time. 3. 4% had disease progression due to MF and another 3. 4% had AML. 3. 4% of patients died due to AML. Median survival was 33. 8years (95% confidence interval 30. 3–35. 5). Initial blood counts, presence of JAK2 and high risk disease status did not correlate with thrombotic risk, risk of death or disease progression. Use of antiplatelet agents and a platelet count ≥1500 × 109/L did not correlate with bleeding risk. Few studies have looked exclusively at young patients with ET. In this group, most patients were asymptomatic and well, ET being diagnosed incidentally. They were predominantly at low risk for thrombosis and other ET-related complications. The period of follow up was comparable to that of other studies and during that time, the rate of complications and risk of disease progression was low. The thrombosis rate of 0. 39% per patient year was less than that reported by other groups (2. 2–2. 6 thromboses/100patients/year) (Leukaemia 2007;21:1218–1223, Clin Appl Thrombosis/Hemostasis 2000;6(1):31–35) but similar to the 0. 74%/patient year reported by Barbui (Blood. Epub. June 13 2012). Overall findings generally complemented those reported by other groups. No risk factors were found to influence the occurrence of complications, but the number of events was small. Follow up of this group of patients over time is essential to see if their disease course remains benign or if complications will increase with time. Soli Deo Gloria Disclosures: Kam: Shire Pharmaceuticals: Consultancy, grant to support the MPN registry Other.

JAK2 V617F, hemostatic polymorphisms, and clinical features as risk factors for arterial thrombotic events in essential thrombocythemia

2008 ◽  
Vol 87 (9) ◽  
pp. 763-765 ◽  
Author(s):  
María J. Moreno ◽  
María L. Lozano ◽  
V. Roldán ◽  
B. Bellosillo ◽  
N. García-Barberá ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Features ◽  
Essential Thrombocythemia ◽  
Jak2 V617f

scholarly journals Decreased Survival and Increased Rate of Fibrotic Progression in Essential Thrombocythemia Chronicled after the FDA Approval Date of Anagrelide

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4287-4287
Author(s):  
Ayalew Tefferi ◽  
Natasha Szuber ◽  
Kebede H. Begna ◽  
Mrinal M. Patnaik ◽  
Michelle A. Elliott ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Survival Data ◽  
Mayo Clinic ◽  
World Health ◽  
Bleeding Complications ◽  
Fda Approval ◽  
Significant Difference ◽  
Risk Distribution ◽  
The Difference

Abstract Background: Anagrelide clinical trials in myeloproliferative neoplasms (MPN) were pioneered by the late Murray N. Silverstein M.D.(1928-1998) of the Mayo Clinic and the first publication involving 20 patients, including 17 with essential thrombocythemia (ET), appeared in 1988 (study launched in October 1985) (N Engl J Med 1988;318:1292). A larger study involving 577 patients, including 335 with ET, was subsequently published in 1992 and led to FDA approval in March 1997 (Am J Med 1992;92:69). Anagrelide has also been evaluated, in controlled studies, for its efficacy and safety as first-line therapy for ET; the results of these studies suggested that anagrelide was not inferior to hydroxyurea, in one study (Blood 2013;121:1720), but might have been harmful to patients in, the second study (N Engl J Med 2005;353:33); in the latter study, patients receiving anagrelide experienced higher incidences of arterial thrombosis, bleeding complications and fibrotic progression. These observations raised significant concern regarding an adverse survival impact of anagrelide in ET; unfortunately, the follow-up period of formal controlled studies were too short to accurately address the particular concern. Methods: The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complication rates in ET. The study population was recruited from a consecutive cohort of adult patients (age ≥18 years) with MPN seen at the Mayo Clinic from 10/27/1967 through 12/29/2017. Diagnosis and determinations of fibrotic and/or leukemic transformations, were in strict accordance with the 2016 World Health Organization criteria (Blood 2016;127:2391). Statistical analyses were based on clinical and laboratory parameters obtained at the time of first referral to the Mayo Clinic which, in the majority of cases, coincided with initial diagnosis. All patients were followed from diagnosis until death or date of last follow-up or contact. Follow-up was until April 2018 and data collected via medical records or in certain cases, by directly contacting patients or their physicians. Survival and time-to-event curves were prepared using the Kaplan-Meier method and compared by the log-rank test. The JMP® Pro 13.0.0 software package was used for all analyses (SAS Institute, Cary, NC, USA). Results: 1,076 patients with ET were considered (median age 58 years; females 63%); international prognostic scoring system for ET (IPSET; Blood 2012;120:1197) risk distribution was 28% high, 42% intermediate and 30% low; driver mutational status was JAK2 61%, CALR 25%, triple-negative 11% and MPL 3%. Comparison of cases diagnosed before (n=433) and after (n=643) the FDA approval date of anagrelide (1997) revealed the former cohort to be younger (median 57 vs 60 years; p=0.003), although the difference in IPSET risk distribution was not significant (p=0.14). Figures 1a, 1b, 1c and 1d illustrate overall (OS), myelofibrosis-free (MFFS), leukemia-free (LFS) and thrombosis-free survival data comparing ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent for OS (p=0.006; HR 1.4, 95% CI 1.1-1.7) and MFFS (p<0.001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; during multivariable analysis that included IPSET and sex, the significant difference in both OS and MFFS were sustained; the difference in OS was most apparent after the first decade of diagnosis with 10- and 20-year survival rates of 75% and 50% for diagnosis prior to 1997 vs 72% and 21% for diagnosis between 1997 and 2017 (figure 1a); the 10- and 20-year risk of fibrotic progression was 3% and 15% for diagnosis prior to 1997 and 14% and 46% for diagnosis after 1997 (figure 1b); there was no impact on LFS (p=0.32; Figure 1c) or TFS (p=0.18; Figure 1d). Similarly stratified survival data in polycythemia vera (n=665) and primary myelofibrosis (n=1,282) showed no impact on survival (p=0.3 and 0.17, respectively). Conclusions: In a retrospective, but otherwise unbiased comparative analysis, we show significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide (1997); the increased risk of fibrotic progression noted is consistent with results of earlier prospective data (N Engl J Med 2005;353:33). Our observations regarding OS requires confirmation in a prospective controlled setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term postoperative care in meningioma patients

2021 ◽  
Author(s):  
Swenja Lüthge ◽  
Dorothee Cäcilia Spille ◽  
Andrea Ulrike Steinbicker ◽  
Stephanie Schipmann ◽  
Eileen Maria Susanne Streckert ◽  
...  
Keyword(s):  
Risk Factors ◽  
Skull Base ◽  
Tumor Recurrence ◽  
Skull Base Tumor ◽  
High Grade ◽  
Entire Cohort ◽  
Long Term Follow Up ◽  
Base Location

Abstract Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05–2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52–3.84; p < .001), high-grade histology (HR: 3.70, 95%CI 2.50–5.47; p < .001), and male gender (HR: 1.46, 95%CI 1.01–2.11; p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17–3.17; p = .010 and HR: 2.02, 95%CI 1.04–3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04–3.38; p = .038 and HR: 2.29, 95%CI 1.07–4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68–3.45; p = .303 and HR: 1.75, 95%CI .52–5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p < .001) but not beyond a follow-up of ≥ 3 years (p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

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