A RETROSPECTIVE COHORT STUDY REPORTING ON THE DISEASE CHARACTERISTICS AND OUTCOMES OF PATIENTS DIAGNOSED UNDER THE AGE OF 50 YEARS WITH PRIMARY OR SECONDARY MYELOFIBROSIS
(Abstract release date: 05/19/16)
EHA Library. Alimam S. 06/09/16; 132913; E1364
Dr. Samah Alimam
Contributions
Contributions
Abstract
Abstract: E1364
Type: Eposter Presentation
Background
Myelofibrosis (MF), a rare clonal haematopoietic disorder is commonly diagnosed in the 6th or 7th decade of life. The clinical and molecular profile of younger patients remains poorly defined.
Aims
In this retrospective study we evaluated patients who were ≤50 years of age at diagnosis with WHO-defined primary MF (PMF), post-essential thrombocythaemia MF (PET-MF) or post-polycythaemia vera MF (PPV-MF) managed at our centre.
Methods
Forty three patients with a median age of 43 years (range 19-50 years) at diagnosis were included; 24/43 (55.8%) were male. Median follow-up was 44 months (range 0-208 months). Twenty (47%) had a diagnosis of PMF, 14/43 (33%) PET-MF and 9/43 (21%) PPV-MF.
Results
Concerning mutations 22/43 (51%) had JAK2V617F, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were ‘triple negative’ (TN). The IPSS and DIPSS scores were low risk in 26/39 (67%) and 26/39 (67%), intermediate-1 in 8/39 (21%) and 11/39 (28%), intermediate-2 in 3/39 (8%) and 2/39 (5%) and high risk in 2/39 (5%) and 7/39 (18%), respectively. Univariate analysis did not demonstrate any significant impact of mutational status upon haemoglobin, leukocytes, platelet count, circulating blasts, red blood cell transfusion need, splenomegaly or constitutional symptoms at diagnosis. Additionally, we did not observe any influence of driver mutation on age at diagnosis, gender, IPSS or DIPSS scores. Comparing JAK2V617F and CALR mutated subjects, there was a significant increase in the presence of palpable splenomegaly in the JAK2V617F mutated patients (p <0.05). TN patients were more like to have a platelet count <100x109/L (p = 0.073), adverse karyotype (p = 0.06), a high DIPSS-plus score (p = 0.076), and the only transformation to acute myeloid leukaemia (AML) occurred in a TN patient. Two thrombotic events occurred: a deep vein thrombosis in a JAK2V617F mutated patient, and a myocardial infarction in CALR mutated patient, giving an overall calculated incidence rate of 1% patient-year. No major bleeding events were identified. Only one patient progressed to AML with an overall calculated incidence rate of 0.5% patient-year. No deaths were recorded during the follow-up period.
Conclusion
The distribution of driver mutations in our cohort of patients with MF diagnosed age less than 50 years differs from that of the overall MF patient population; we report that 51% of patients had JAK2V617F mutation vs 58-64.7% for the broader patient population, 42% CALR mutated vs 22.7-25%, 0% MPL mutated vs 4-8.3% (1,2). The frequency of TN patients mirrors that of the wider MF population, 7% in our cohort vs 8.6-8.7% in the literature (1,2). Although we were not able to demonstrate any significant impact of driver mutation status on age, gender or laboratory parameters, we recorded a higher incidence of splenomegaly in JAK2V617F mutated patients compared to CALR mutated patients, (P=0.047). We found that TN status appeared to be associated with higher risk profile and transformation to AML.Our findings suggest that younger MF subjects may have a higher frequency of CALR mutations and a more indolent disease course i.e. low IPSS and DIPPS score, lower incidences of thromboembolic events and with less evidence of negative prognostic variables and disease progression compared to the general MF population.References:
1.Tefferi et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7
2.Rumi et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062-9
Session topic: E-poster
Keyword(s): Myelofibrosis
Type: Eposter Presentation
Background
Myelofibrosis (MF), a rare clonal haematopoietic disorder is commonly diagnosed in the 6th or 7th decade of life. The clinical and molecular profile of younger patients remains poorly defined.
Aims
In this retrospective study we evaluated patients who were ≤50 years of age at diagnosis with WHO-defined primary MF (PMF), post-essential thrombocythaemia MF (PET-MF) or post-polycythaemia vera MF (PPV-MF) managed at our centre.
Methods
Forty three patients with a median age of 43 years (range 19-50 years) at diagnosis were included; 24/43 (55.8%) were male. Median follow-up was 44 months (range 0-208 months). Twenty (47%) had a diagnosis of PMF, 14/43 (33%) PET-MF and 9/43 (21%) PPV-MF.
Results
Concerning mutations 22/43 (51%) had JAK2V617F, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were ‘triple negative’ (TN). The IPSS and DIPSS scores were low risk in 26/39 (67%) and 26/39 (67%), intermediate-1 in 8/39 (21%) and 11/39 (28%), intermediate-2 in 3/39 (8%) and 2/39 (5%) and high risk in 2/39 (5%) and 7/39 (18%), respectively. Univariate analysis did not demonstrate any significant impact of mutational status upon haemoglobin, leukocytes, platelet count, circulating blasts, red blood cell transfusion need, splenomegaly or constitutional symptoms at diagnosis. Additionally, we did not observe any influence of driver mutation on age at diagnosis, gender, IPSS or DIPSS scores. Comparing JAK2V617F and CALR mutated subjects, there was a significant increase in the presence of palpable splenomegaly in the JAK2V617F mutated patients (p <0.05). TN patients were more like to have a platelet count <100x109/L (p = 0.073), adverse karyotype (p = 0.06), a high DIPSS-plus score (p = 0.076), and the only transformation to acute myeloid leukaemia (AML) occurred in a TN patient. Two thrombotic events occurred: a deep vein thrombosis in a JAK2V617F mutated patient, and a myocardial infarction in CALR mutated patient, giving an overall calculated incidence rate of 1% patient-year. No major bleeding events were identified. Only one patient progressed to AML with an overall calculated incidence rate of 0.5% patient-year. No deaths were recorded during the follow-up period.
Conclusion
The distribution of driver mutations in our cohort of patients with MF diagnosed age less than 50 years differs from that of the overall MF patient population; we report that 51% of patients had JAK2V617F mutation vs 58-64.7% for the broader patient population, 42% CALR mutated vs 22.7-25%, 0% MPL mutated vs 4-8.3% (1,2). The frequency of TN patients mirrors that of the wider MF population, 7% in our cohort vs 8.6-8.7% in the literature (1,2). Although we were not able to demonstrate any significant impact of driver mutation status on age, gender or laboratory parameters, we recorded a higher incidence of splenomegaly in JAK2V617F mutated patients compared to CALR mutated patients, (P=0.047). We found that TN status appeared to be associated with higher risk profile and transformation to AML.Our findings suggest that younger MF subjects may have a higher frequency of CALR mutations and a more indolent disease course i.e. low IPSS and DIPPS score, lower incidences of thromboembolic events and with less evidence of negative prognostic variables and disease progression compared to the general MF population.References:
1.Tefferi et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7
2.Rumi et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062-9
Session topic: E-poster
Keyword(s): Myelofibrosis
Abstract: E1364
Type: Eposter Presentation
Background
Myelofibrosis (MF), a rare clonal haematopoietic disorder is commonly diagnosed in the 6th or 7th decade of life. The clinical and molecular profile of younger patients remains poorly defined.
Aims
In this retrospective study we evaluated patients who were ≤50 years of age at diagnosis with WHO-defined primary MF (PMF), post-essential thrombocythaemia MF (PET-MF) or post-polycythaemia vera MF (PPV-MF) managed at our centre.
Methods
Forty three patients with a median age of 43 years (range 19-50 years) at diagnosis were included; 24/43 (55.8%) were male. Median follow-up was 44 months (range 0-208 months). Twenty (47%) had a diagnosis of PMF, 14/43 (33%) PET-MF and 9/43 (21%) PPV-MF.
Results
Concerning mutations 22/43 (51%) had JAK2V617F, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were ‘triple negative’ (TN). The IPSS and DIPSS scores were low risk in 26/39 (67%) and 26/39 (67%), intermediate-1 in 8/39 (21%) and 11/39 (28%), intermediate-2 in 3/39 (8%) and 2/39 (5%) and high risk in 2/39 (5%) and 7/39 (18%), respectively. Univariate analysis did not demonstrate any significant impact of mutational status upon haemoglobin, leukocytes, platelet count, circulating blasts, red blood cell transfusion need, splenomegaly or constitutional symptoms at diagnosis. Additionally, we did not observe any influence of driver mutation on age at diagnosis, gender, IPSS or DIPSS scores. Comparing JAK2V617F and CALR mutated subjects, there was a significant increase in the presence of palpable splenomegaly in the JAK2V617F mutated patients (p <0.05). TN patients were more like to have a platelet count <100x109/L (p = 0.073), adverse karyotype (p = 0.06), a high DIPSS-plus score (p = 0.076), and the only transformation to acute myeloid leukaemia (AML) occurred in a TN patient. Two thrombotic events occurred: a deep vein thrombosis in a JAK2V617F mutated patient, and a myocardial infarction in CALR mutated patient, giving an overall calculated incidence rate of 1% patient-year. No major bleeding events were identified. Only one patient progressed to AML with an overall calculated incidence rate of 0.5% patient-year. No deaths were recorded during the follow-up period.
Conclusion
The distribution of driver mutations in our cohort of patients with MF diagnosed age less than 50 years differs from that of the overall MF patient population; we report that 51% of patients had JAK2V617F mutation vs 58-64.7% for the broader patient population, 42% CALR mutated vs 22.7-25%, 0% MPL mutated vs 4-8.3% (1,2). The frequency of TN patients mirrors that of the wider MF population, 7% in our cohort vs 8.6-8.7% in the literature (1,2). Although we were not able to demonstrate any significant impact of driver mutation status on age, gender or laboratory parameters, we recorded a higher incidence of splenomegaly in JAK2V617F mutated patients compared to CALR mutated patients, (P=0.047). We found that TN status appeared to be associated with higher risk profile and transformation to AML.Our findings suggest that younger MF subjects may have a higher frequency of CALR mutations and a more indolent disease course i.e. low IPSS and DIPPS score, lower incidences of thromboembolic events and with less evidence of negative prognostic variables and disease progression compared to the general MF population.References:
1.Tefferi et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7
2.Rumi et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062-9
Session topic: E-poster
Keyword(s): Myelofibrosis
Type: Eposter Presentation
Background
Myelofibrosis (MF), a rare clonal haematopoietic disorder is commonly diagnosed in the 6th or 7th decade of life. The clinical and molecular profile of younger patients remains poorly defined.
Aims
In this retrospective study we evaluated patients who were ≤50 years of age at diagnosis with WHO-defined primary MF (PMF), post-essential thrombocythaemia MF (PET-MF) or post-polycythaemia vera MF (PPV-MF) managed at our centre.
Methods
Forty three patients with a median age of 43 years (range 19-50 years) at diagnosis were included; 24/43 (55.8%) were male. Median follow-up was 44 months (range 0-208 months). Twenty (47%) had a diagnosis of PMF, 14/43 (33%) PET-MF and 9/43 (21%) PPV-MF.
Results
Concerning mutations 22/43 (51%) had JAK2V617F, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were ‘triple negative’ (TN). The IPSS and DIPSS scores were low risk in 26/39 (67%) and 26/39 (67%), intermediate-1 in 8/39 (21%) and 11/39 (28%), intermediate-2 in 3/39 (8%) and 2/39 (5%) and high risk in 2/39 (5%) and 7/39 (18%), respectively. Univariate analysis did not demonstrate any significant impact of mutational status upon haemoglobin, leukocytes, platelet count, circulating blasts, red blood cell transfusion need, splenomegaly or constitutional symptoms at diagnosis. Additionally, we did not observe any influence of driver mutation on age at diagnosis, gender, IPSS or DIPSS scores. Comparing JAK2V617F and CALR mutated subjects, there was a significant increase in the presence of palpable splenomegaly in the JAK2V617F mutated patients (p <0.05). TN patients were more like to have a platelet count <100x109/L (p = 0.073), adverse karyotype (p = 0.06), a high DIPSS-plus score (p = 0.076), and the only transformation to acute myeloid leukaemia (AML) occurred in a TN patient. Two thrombotic events occurred: a deep vein thrombosis in a JAK2V617F mutated patient, and a myocardial infarction in CALR mutated patient, giving an overall calculated incidence rate of 1% patient-year. No major bleeding events were identified. Only one patient progressed to AML with an overall calculated incidence rate of 0.5% patient-year. No deaths were recorded during the follow-up period.
Conclusion
The distribution of driver mutations in our cohort of patients with MF diagnosed age less than 50 years differs from that of the overall MF patient population; we report that 51% of patients had JAK2V617F mutation vs 58-64.7% for the broader patient population, 42% CALR mutated vs 22.7-25%, 0% MPL mutated vs 4-8.3% (1,2). The frequency of TN patients mirrors that of the wider MF population, 7% in our cohort vs 8.6-8.7% in the literature (1,2). Although we were not able to demonstrate any significant impact of driver mutation status on age, gender or laboratory parameters, we recorded a higher incidence of splenomegaly in JAK2V617F mutated patients compared to CALR mutated patients, (P=0.047). We found that TN status appeared to be associated with higher risk profile and transformation to AML.Our findings suggest that younger MF subjects may have a higher frequency of CALR mutations and a more indolent disease course i.e. low IPSS and DIPPS score, lower incidences of thromboembolic events and with less evidence of negative prognostic variables and disease progression compared to the general MF population.References:
1.Tefferi et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7
2.Rumi et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062-9
Session topic: E-poster
Keyword(s): Myelofibrosis
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