Contributions
Abstract: PB2291
Type: Publication Only
Background
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) are a heterogenous group of disorders characterized by cellular proliferation of one or more hematopoietic cell lines. In 2016, after revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, the detection of somatic mutations in three driver genes, JAK2, CALR and MPL was introduced as the major diagnostic criteria for MPN patients. Molecular profiling in combination with morphological and hematologic abnormalities will allow accurate evaluation of MPN subtypes and monitoring of response to the treatment.
Aims
In this study we analyzed clinical outcomes of MPN patients with detected JAK2, CALR and MPL mutations from Bosnia and Herzegovina as well as the correlation between clinical parameters, presence of the mutation and disease severity.
Methods
MPN patients (n=90) who were diagnosed in the period from January 2000 to September 2017 and treated at the Clinical Center of the University of Sarajevo Bosnia and Herzegovina, were included in this study. Patients were categorized according to four different MPN subtypes: polycythemia vera (PV, n=29), essential thrombocythemia (ET, n=40), primary myelofibrosis (PMF, n=3) and MPN-unclassifiable (n=18). Standard patients' variables were collected including full blood count, bone marrow characteristics, hepato/splenomegaly, and overall survival. qPCR was performed for JAK2V617F detection. PCR and agarose gel electrophoresis were used for detection of CALR mutation including wild-type CALR (product: 357 bp), type 1 (product: 305 bp) and type 2 (product: 272 bp) mutations. Detection of MPL mutation was performed using capillary sequencing, to detect type 1 (W515L) and type 2 (W515K) mutations. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test.
Results
Ninety MPN patients were enrolled in this study (50% were males). Median follow-up period was 63 months, and the median age at diagnosis was 61 years. Regarding clinical characteristics of studied cohort, 10% of patients had hypercellular bone marrow, while splenomegaly and hepatomegaly were detected in 16% (14/90) and 7% (6/90) of patients, respectively. The overall JAK2, CALR and MPL mutation frequencies in our cohort were 60%, 10%, and 3%, respectively. For PV patients (n=29), 76% carried JAK2V617F mutation. For ET patients (n=29), 59% of patients were positive for JAK2V617F, 24% of patients carried CALR type 1 or 2 mutation, and 3% carried MPL type 2 mutation, while 14% of patients were triple negative. CALR type 2 mutation was slightly more predominant than CALR type 1. In PMF patients (n=3), 33% of patients carried JAK2V617F, 33% of patients carried CALR and 33% of patients carried MPL type 1 mutation. In the group of MPN-unclassifiable patients, 44% (8/18) carried JAK2V617F mutation. Out of 90 patients, 18 died during the observed period of time (PV n=8, ET n= 3; PMF n=0, MPN-u n=7). In all MPN subtypes, Kaplan-Meier survival analysis showed that there were no statistically significant differences in overall survival between patients with and without detected driver mutation (p>0.05).
Conclusion
Determination of the mutational status of JAK2, CALR and MPL is important for diagnosis and treatment. We found that overall survival did not depend on the presence of the tested mutations in MPN patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Clinical outcome, Myeloproliferative disorder
Abstract: PB2291
Type: Publication Only
Background
Philadelphia-negative classical myeloproliferative neoplasms (MPNs) are a heterogenous group of disorders characterized by cellular proliferation of one or more hematopoietic cell lines. In 2016, after revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, the detection of somatic mutations in three driver genes, JAK2, CALR and MPL was introduced as the major diagnostic criteria for MPN patients. Molecular profiling in combination with morphological and hematologic abnormalities will allow accurate evaluation of MPN subtypes and monitoring of response to the treatment.
Aims
In this study we analyzed clinical outcomes of MPN patients with detected JAK2, CALR and MPL mutations from Bosnia and Herzegovina as well as the correlation between clinical parameters, presence of the mutation and disease severity.
Methods
MPN patients (n=90) who were diagnosed in the period from January 2000 to September 2017 and treated at the Clinical Center of the University of Sarajevo Bosnia and Herzegovina, were included in this study. Patients were categorized according to four different MPN subtypes: polycythemia vera (PV, n=29), essential thrombocythemia (ET, n=40), primary myelofibrosis (PMF, n=3) and MPN-unclassifiable (n=18). Standard patients' variables were collected including full blood count, bone marrow characteristics, hepato/splenomegaly, and overall survival. qPCR was performed for JAK2V617F detection. PCR and agarose gel electrophoresis were used for detection of CALR mutation including wild-type CALR (product: 357 bp), type 1 (product: 305 bp) and type 2 (product: 272 bp) mutations. Detection of MPL mutation was performed using capillary sequencing, to detect type 1 (W515L) and type 2 (W515K) mutations. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test.
Results
Ninety MPN patients were enrolled in this study (50% were males). Median follow-up period was 63 months, and the median age at diagnosis was 61 years. Regarding clinical characteristics of studied cohort, 10% of patients had hypercellular bone marrow, while splenomegaly and hepatomegaly were detected in 16% (14/90) and 7% (6/90) of patients, respectively. The overall JAK2, CALR and MPL mutation frequencies in our cohort were 60%, 10%, and 3%, respectively. For PV patients (n=29), 76% carried JAK2V617F mutation. For ET patients (n=29), 59% of patients were positive for JAK2V617F, 24% of patients carried CALR type 1 or 2 mutation, and 3% carried MPL type 2 mutation, while 14% of patients were triple negative. CALR type 2 mutation was slightly more predominant than CALR type 1. In PMF patients (n=3), 33% of patients carried JAK2V617F, 33% of patients carried CALR and 33% of patients carried MPL type 1 mutation. In the group of MPN-unclassifiable patients, 44% (8/18) carried JAK2V617F mutation. Out of 90 patients, 18 died during the observed period of time (PV n=8, ET n= 3; PMF n=0, MPN-u n=7). In all MPN subtypes, Kaplan-Meier survival analysis showed that there were no statistically significant differences in overall survival between patients with and without detected driver mutation (p>0.05).
Conclusion
Determination of the mutational status of JAK2, CALR and MPL is important for diagnosis and treatment. We found that overall survival did not depend on the presence of the tested mutations in MPN patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Clinical outcome, Myeloproliferative disorder