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La trombocitemia esencial (TE) es una neoplasia mieloproliferativa crónica BCR-ABL negativa, caracterizada por la producción excesiva de plaquetas clonales. La prevalencia mundial varía, siendo aproximadamente 38 a 57 por 100.000. El tratamiento de la TE tiene como objetivo reducir el riesgo de trombosis o complicaciones hemorrágicas.Objetivo: el objetivo de la presente revisión panorámica es evaluar la evidencia actual sobre el tratamiento citoreductor de la trombocitemia esencial disponible en Colombia. Métodos: se realizó una búsqueda estructurada de literatura respecto a la efectividad y seguridad de los tratamientos citoreductores en el paciente con trombocitemia esencial. A partir de la pregunta de investigación con estructura PICO, se definieron los criterios de inclusión: pacientes con trombocitemia esencial, en manejo con Anagrelida y/o Hidroxiurea. Se incluyeron estudios de revisiones sistemáticas, metanálisis, ensayos clínicos aleatorizados. Resultados: se realizó una búsqueda en MEDLINE, EMBASE, LILACS, Cochrane Database of systematic Reviews, que arrojó 119 referencias de las cuales se incluyeron cuatro estudios, que cumplían con las características de la población, intervención y comparador. Conclusiones: la terapia citorreductora es fundamental para el manejo de la trombocitemia esencial. La evidencia sugiere que tanto Hidroxiurea como Anangrelida son agentes que brindan una protección similar contra eventos trombo-hemorrágicos clínicamente significativos.

espanolLa poliglobulia o eritrocitosis se refiere al aumento de la concentracion de hemoglobina y hematocrito en sangre periferica. La eritropoyetina, producida en un 95% en las celulas renales, es la encargada de la regulacion de la eritropoyesis debido a la hipoxia y se encuentra elevada en las eritrocitosis secundarias. La eritrocitosis primaria mas importante es la policitemia vera, una neoplasia mieloproliferativa cronica que produce eritrocitosis, independientemente de la eritropoyetina, debido a una mutacion de los precursores eritroides. Se establece por un aumento de la hemoglobina superior a 16,5 g/dl en el hombre y 16 g/dl en la mujer. El diagnostico etiologico es fundamental para proporcionar un adecuado manejo al paciente. EnglishPolycythemia or erythrocytosis refers to an increase in hemoglobin and hematocrit concentration in peripheral blood. The erythopoietin, produced in 95% of renal cells, is in charge of erythropoiesis regulation due to hypoxia and is elevated in secondary erythrocytosis. The most important primary erythrocytosis is polycythemia vera, a chronic myeloproliferative neoplasm that produces erythrocytosis independently of erythropoietin due to a mutation in erythroid progenitor cells. A diagnosis is established based on an increase in hemoglobin above 16.5 g/dl in men and 16 g/dl in women. An etiological diagnosis is fundamental for an appropriate management of the patient.

Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm (MPN). A newly developed PV treatment option, ropeginterferon alfa-2b, contains recombinant human alfa monoisomer as an active ingredient, resulting in a novel pharmacologic profile and improved tolerability. Efficacy studies conclude remarkable long-term hematological response and sustained JAK2V617F allele burden reduction. Ropeginterferon alfa-2b compound has been approved for the treatment of polycythemia vera without symptomatic splenomegaly.Current clinical trials are investigating the role of ropeginterferon alfa-2b in the first-line setting of treatment for PV. The safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues are also discussed of ropeginterferon alfa-2b.Ropeginterferon alfa-2b is a targeted therapeutic option in the treatment of PV, representing a significant improvement compared to conventional cytoreductive therapies. The single isomer entity of the recombinant human interferon alfa-2b and the mono-pegylation method imparts favorable properties to the compound. The use of ropeginterferon alfa-2b allows extended dosing interval, reduces side effects, and may increase the overall survival of PV patients by reducing the risk of progression to myelofibrosis or acute leukemia. Clinical data suggests that the compound may provide a disease-modifying option for PV patients with asymptomatic splenomegaly.

BACKGROUND AND OBJECTIVE MYELOFIBROSIS: is an infrequent chronic myeloproliferative neoplasm. We aimed to describe the clinico-biological characteristics, treatment, and evolutive course of myelofibrosis patients in Spain.; MATERIAL AND METHODS: A total of 1,000 patients from the Spanish Registry of Myelofibrosis diagnosed with primary (n=641) or secondary (n=359) myelofibrosis were analysed.; RESULTS: Median age was 68 years. The frequency of constitutional symptoms, moderate to severe anaemia (Hb

Acute myeloid leukemia (AML) with specific genetic abnormalities is a clinically, biologically, and prognostically distinct category with some of the entities in it displaying characteristic morphology. AML with t(8:21) is one such subtype carrying favorable prognosis with specific blast morphology. Eosinophilia, characteristically, has been described till date in AML with inv (16); however, hypereosinophilia with prominent dysplastic features has yet not been seen with any AML subtype. We report the case of an 8-year-old child presenting with massive splenomegaly, hypereosinophilia, and low marrow blast percentage. The initial clinical and hematological impression was that of a chronic myeloproliferative neoplasm, which was later diagnosed as AML with t(8:21) with the help of cytogenetic studies. The case report highlights the unusual and extremely rare presentation of this AML subtype and the importance of cytogenetic studies in definite categorization, especially in cases with overlapping morphological and immunophenotypic findings.

Background/aim GDF15, hepcidin and mitoferrin-1 (mfrn-1) are proteins involved in systemic iron regulation. There are no studies in the literature demonstrating the serum mfrn-1 levels in polycythemia vera (PV) and essential thrombocythemia (ET) patients. The aim of this study was to investigate GDF15, hepcidin and mfrn-1 levels in PV and ET patients. Materials and methods Ten PV, 17 ET patients, and 27 healthy controls (HCs) were enrolled. GDF15, hepcidin and mfrn-1 values were measured with enzyme-linked immunosorbent assay (ELISA). Results GDF15 levels were higher in the myeloproliferative neoplasm (MPN) group (P = 0.002). Hepcidin levels were not different between MPN patients and HCs. The mfrn-1 levels were lower in MPN patients (P = 0.039). Hepcidin, GDF15, and mfrn-1 levels were not different between PV and ET patients. mfrn-1 levels were lower in ET patients than HCs (P = 0.038). Conclusion Increased erythropoiesis in MPNs may lead to high GDF15 levels in these patients. However, hepcidin was not suppressed despite the increased GDF15 levels and erythropoiesis in these patients. Decrease in mfrn-1 in MPNs can be the result of its increased turnover due to increased myelopoiesis. It can be hypothesized that similar hepcidin levels in patients and controls and low mfrn-1 levels in patients may be a defense mechanism against erythroid activity and thromboembolic complications.

IntroductionThe Coronavirus disease 2019 (COVID-19) pandemic and the resulting social distancing, determined a reduction in access to care and limitations of individual freedom, with a consequent strong impact on quality of life (QoL), anxiety levels and medical management of onco-hematological people. In particular, in the case of patients with chronic myeloproliferative neoplasm (MPN), concern about SARS-CoV-2 infection added to the burden of symptoms (BS) which already weights on the QoL of these patients. We designed a cross-sectional survey in order to investigate the impact of the COVID-19 pandemic on status of anxiety, BS and QoL in MPN patients.MethodsWe analyzed the anxiety levels using the Zung Self-Rating Anxiety Scale (SAS); BS modifications were studied using the 18 items of the Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF].Results132 people answered to the survey: 27 (20.4%) patients achieved a moderate to marked anxiety index value: this group described a greater worsening of symptoms than the rest of the cohort (p ConclusionThis study first showed that the COVID-19 quarantine had a significant negative impact on the level of anxiety and BS in MPN patients. We identified female gender, absence of physical activity, the need for frequent visit to the hospital and the absence of a direct access to healthcare staff as the main factors associated to a higher anxiety index and worst BS.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by a persistently elevated platelet count in the absence of a secondary cause. The clinical consequences of uncontrolled thrombocytosis can include both thrombosis and hemorrhage. Patients with features conferring a “high risk” of vascular events benefit from reduction of the platelet count through cytoreductive therapy. The management of patients who lack such high-risk features has until recently been less well defined, but it is now apparent that many require minimal or even no intervention. In this review, we discuss the diagnostic pathway for younger patients with unexplained thrombocytosis, including screening molecular investigations, the role of bone marrow biopsy, and investigations in those patients negative for the classic myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL). We discuss conventional and novel risk stratification methods in essential thrombocythemia and how these can be best applied in clinical practice, particularly in the era of more comprehensive genomic testing. The treatment approach for “low risk” patients is discussed including antiplatelets and the options for cytoreductive therapy, if indicated, together with areas of clinical need for future study.

Polycythemia vera is a chronic myeloproliferative neoplasm, which is primarily characterized by elevated erythrocyte count with the risk of thrombosis, hemorrhage, and vasomotor symptoms. More common reported about bleeding events are gastrointestinal, mucosal, and cutaneous bleeding. Spontaneous cerebral hemorrhage/bleeding is seldom reported. Here, we report the case of a 50-year-old female with polycythemia vera who developed a spontaneous cerebral hemorrhage. She improved significantly after hydroxyurea agent and red cell apheresis, and the hematocrit decreased from 74% to 40%.

Primary myelofibrosis is a chronic myeloproliferative neoplasm that may cause debilitating symptoms, which can be improved with the use of Ruxolitinib, a Janus kinase 2 inhibitor. However, this agent has significant immunomodulatory effects which may increase the risk for infections.We searched the literature and our institutional electronic medical record for reported cases of infections in adult patients on ruxolitinib treatment.We found 28 cases in our literature search and 4 cases from our Institution for a total of 32 cases. The most common infection was tuberculosis in 11/32 cases (34%), followed by cryptococcal infection in 3/32 (9%) and hepatitis B virus reactivation in 3/32 (9%).Opportunistic infections associated with ruxolitinib use are increasingly reported in the literature; further studies should investigate the role of systematic screening and prophylaxis against infections in this subset of patients.

Mutations of JAK2V617F, CALR, and MPL genes confirm the diagnosis of myeloproliferative neoplasm (MPN). This study aims to determine the genetic profile of JAK2V617F, CALR exon 9 Type 1 (52 bp deletion) and Type 2 (5 bp insertion), and MPL W515 L/K genes among Malaysian patients and correlate these mutations with clinical and hematologic parameters in MPN. Mutations of JAK2V617F, CALR, and MPL were analyzed in 159 Malaysian patients using allele-specific polymerase chain reaction, including 76 polycythemia vera (PV), 41 essential thrombocythemia (ET), and 42 primary myelofibrosis (PMF) mutations, and the demographics of the patients were retrieved. The result showed that 73.6% JAK2V617F, 5.66% CALR, and 27.7% were triple-negative mutations. No MPL W515L/K mutation was detected. In ET and PMF, the predominance type was the CALR Type 1 mutation. In JAK2V617F mutant patients, serum LDH was significantly higher in PMF compared to PV and ET. PV has a higher risk of evolving to post PV myelofibrosis compared to ET. A thrombotic event at initial diagnosis of 40.9% was high compared to global incidence. Only one PMF patient had a CALR mutation that transformed to acute myeloid leukemia. JAK2V617F and CALR mutations play an important role in diagnostics. Hence, every patient suspected of having a myeloproliferative neoplasm should be screened for these mutations.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by thrombocytosis, increased risk of thrombotic/hemorrhagic events and clonal evolution into blast phase or myelofibrosis. Areas covered: The authors will discuss biology, diagnosis, prognosis, therapy, and outcome of ET. An accurate molecular-morphologic assessment is necessary in order to properly establish diagnosis and prognosis of ET. Stratification for thrombosis prediction is essential, and IPSET-t model is widely applied. The current treatment strategy is directed to lower the rate of vascular events using cytoreduction in patients at high risk. Prophylactic low dose aspirin indication is more uncertain. To date, therapies for patients who are resistant or intolerant to first-line treatments are scarce. Overall, life expectancy indicates an indolent disease, but IPSET model helps in predicting survival at the time of diagnosis. Expert opinion: Challenging for the future will be to share criteria for ET diagnosis with the community. New insights into the molecular pathogenesis of the disease will improve the prediction of clonal evolution and outcome, and lead to the use of disease-modifying treatments.

Polycythemia Vera (PV) is a Philadelphia-negative chronic myeloproliferative neoplasm (MPN) mainly characterized by erythrocytosis. In this report we describe a case of severe cutaneous toxicity in patients with PV treated with hydroxyurea. A 72-year-old woman diagnosed with PV with V617F mutation of JAK2 performed more than 10 years before and treated with hydroxyurea plus phlebotomies and low-dose ASA for about 7 years addressed our center for the appearance of serious dermatitis at the face symptomatic for severe itch. The patient underwent a dermatology visit with diagnosis of desquamative dermatitis due to iatrogenic cause related to the use of hydroxyurea. HU was stopped for a month with no improvement after a month of wash-out. Ruxolitinib was prescribed at a dose of 20 mg per day, in order to control hypercytosis and considering the severe intolerance to hydroxyurea. Ruxolitinib allowed not only to reduce the haematocrit, reaching the target value of 45%, and control thrombocytosis, but also to switch off the severe itch and to completely resolve skin toxicity.

We present a rare case of multiple granulocytic sarcoma in a young African woman in blast phase of chronic myeloproliferative neoplasm. Fine needle aspiration cytology of the sarcoma, peripheral blood film and bone marrow aspiration cytology were consistent with chronic myeloid leukaemia in blast phase. Objective To present a rare case of multiple granulocytic sarcoma as extramedullary manifestation of chronic myeloproliferative neoplasm in the context of creating awareness about this rare unusual presentation.

There are lot of grey zones in Philadelphia negative chronic myeloproliferative neoplasms (CMPNs) and that's the reason they are in hit list of researchers. Having a spectrum of disorders their diagnosis is very important and especially to differentiate from each other since they overlap with each other in many ways. Diagnosis doesn't start from lab but with clinical phenotype. Clinical phenotype not only able to provide us the diagnosis but also helps in management of the disease per se. When diagnosis comes, the old timer but an evergreen morphology plays an important role which along with the newer generation tool "molecular" helps in differentiating these disorders. Lot of studies have already come up from the world. Indian data has also started coming up. When we say about the Indian data nothing holds more important role than Indian Society of Haematology and Blood Transfusion, ISHBT. This small review will cover all papers with BCR-ABL negative CMPNs which were presented at the annual national conference of the ISHBT (Haematocon 2017) which was conducted at Guwahati. These abstract papers from various reputed institutes and centres will provide a short academic journey towards ongoing research activities at these places and will able to guide us regarding Philadelphia negative CMPNs and also stimulate our brain for some left or conflicted areas.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by erythrocytosis and clonal Janus kinase 2 (JAK2) V617F or JAK2 exon 12 mutations. The 2016 World Health Organization update has incorporated clinical and laboratory findings, molecular testing, and bone marrow pathology in its new classification, thereby improving the sensitivity to detect patients with PV and distinguishing the disease from other MPNs. Crystal structures and modeling of the JAK2 molecule have offered insight into possible therapeutic strategies with novel small molecules. These small molecules provide precision by affecting the mutated protein over the activity of wild type protein. Newer molecular techniques, especially next-generation sequencing, are revolutionizing molecular biology with the identification of somatic mutations modifying the course and prognosis of the disease. These mutations are found to have a potential role in responsiveness to therapy and may guide therapy decisions as well. Here we review recent advances in the clinical features, the diagnosis, the approaches, and the treatment of PV.

Thromboses are the most important preventable risk factors for morbidity and mortality in myeloproliferative neoplasms (MPN). We here performed a retrospective cross sectional study of patients with a diagnosis of Philadelphia negative MPN and a prior history of thrombosis, analyzed from electronic charts. Among a cohort of 260 patients with MPNs (78PV, 102ET, 80 MF), forty four were found triple negative for JAK-2, calreticulin and MPL gene mutations. Sixty-nine (26.54%) patients (29F, 40M) had a personal past clinical history of arterial or venous thrombosis. Among patients with thrombosis, 13(18.8%) cases (11ET, 2MF) were triple negative (median age:60 years). Most events, in particular in triple negative patients, occurred within 18 months before overt MPN . At the time of thrombosis diagnosis, only a minority of patients showed blood tests abnormalities suggestive of MPN or indicating hematological consultation(Figure). Triple negative MPNs may represent a distinct entity with peculiar clinical course and risk factors.

This work was funded by the Spanish Ministry of Economy and Competitiveness (grant SAF2013-45836-R). J.G-A. is supported by a fellowship from the Spanish Ministry of Education. We thank Fundación Caja Rural de Asturias for financial collaborative support to Laboratorio de Oncología Molecular (HUCA). The Instituto Universitario de Oncología is supported by Fundación Bancaria Caja de Ahorros de Asturias, Spain.

Systemic mastocytosis (SM) is a rare chronic myeloproliferative neoplasm characterized by the accumulation of morphologically and phenotypically abnormal mast cells in affected organs. The clinical...

7055 Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN), covering broad spectrum of clinical scenarios, from asymptomatic patients with only isolated high platelets to highly morbid patients in late stage disease. Due to heterogenous patient population, designing clinical studies in ET is difficult, and after anagrelide there was no new drug approval to treat ET during the past 15 years, thus, high unmet medical to treat patients with ET remains. Interferons alpha (IFNa) are known to have beneficial effects in MPN (Kiladjian et al, 2016). P1101 is a next generation monopegylated IFNa, developed specifically to treat MPNs, including ET. Methods: External published clinical data in ET were analyzed to design optimal clinical study. Proposed endpoints are meant to cover all relevant clinical aspects of ET, and suffice for a regulatory relevant pivotal clinical study. Results: Composite primary endpoint scale is based on modified ELN criteria. Short term study endpoints should have clinical meaningfulness at time of measurement but also predict the later outcomes. The scale consists of: normalization of platelets (

Essential thrombocythemia is a chronic myeloproliferative neoplasm characterized by sustained thrombocytosis, bone marrow megakaryocytic hyperplasia and an increased risk of thrombosis and hemorrhage. The goal of treatment is to prevent the development of vascular complications without increasing the risk of transformation. Patients aged>60 years or a history of thrombosis have a high risk of thrombosis while those with a platelet count>1,500 x 10(9)/l have a higher risk of hemorrhage. Patients with low-risk essential thrombocythemia can be managed appropriately with low-dose of acetylsalicylic acid or even observation only, while patients with a high-risk disease are candidates to receive cytoreductive treatment, hydroxyurea being the first choice therapy. Anagrelide is the most suitable option for patients with resistance or intolerance to hydroxyurea. All patients must be submitted to a rigorous control of cardiovascular risk factors.

Introduction Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN), characterized by the clonal proliferation of megakaryocytes in the bone marrow and high platelet count in the peripheral blood. ET has been associated with transformation to acute myeloid leukemia, myelodysplastic syndrome, chronic lymphoytic leukemia, and other MPNs, especially primary myelofibrosis. The association between multiple myeloma (MM) and ET is infrequent. Only a few cases in the medical literature have been demon

Hydroxyurea (HU) is a drug frequently used in the treatment of chronic myeloproliferative neoplasms. The most common side effects of this drug are pancytopenia, digestive and skin disorders. Respiratory complications are rare and there are less than 20 cases described, only 5 of which underwent an anatomopathological study. We present the case of a patient with chronic myeloproliferative neoplasm who developed interstitial pneumonitis probably due to HU according to histological study.

Although hydroxyurea is considered the first-line cytoreductive therapy in high-risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25% of patients develop resistance or intolerance and they need an alternative therapy. Anagrelide is the treatment of choice in patients with essential thrombocythemia intolerant or with resistance to hydroxyurea. Anagrelide is usually well tolerated. Although there is concern about the increased risk of cardiac side effects, in most cases these are mild, and easily manageable. In this paper, the available evidence about the management of patients with myeloproliferative neoplasms, with a special focus on the side effects of drug therapies is reviewed.

Multiple myeloma is a neoplastic disease characterized by neoplastic proliferation of plasma cells and monoclonal protein expression and related tissue damage. In the presence of overt clinical signs, the disease can easily be diagnosed, however in order to diagnose atypical cases, further investigation is needed with high clinical suspicion. Essential thrombocythemia is a chronic myeloproliferative neoplasm which leads to an increase in platelet count with circulating megakaryocytes. When compared with other myeloproliferative neoplasms the prognosis is better and is more common in women. Herein we report a 68-year old patient suffering of essential thombocythemia, who later in follow-up developed multiple myelomas.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm defined by erythrocytosis and often accompanied by leukocytosis and thrombocytosis. Current treatment options, including IFN-α and hydroxyurea, effectively manage PV in many patients. However, some high-risk patients, particularly those who become hydroxyurea-intolerant/resistant, may benefit from IFN-α or new treatment options. A better understanding of PV pathophysiology, including the role of the JAK/STAT pathway, has inspired the development of new therapies. Several JAK inhibitors directly target JAK/STAT pathway activation and have been evaluated in Phase II/III trials with promising results. Pegylated variants of IFN-α, which reduce dosing frequency and toxicity associated with recombinant IFN-α, have yielded favorable efficacy results in Phase II trials. Finally, histone deacetylase inhibitors have been developed to manage PV at the level of chromatin-regulated gene expression. The earliest Phase III results from these next-generation therapies are expected in 2014.

Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8 %) than in sporadic (62 %) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN. © 2014, Springer-Verlag Berlin Heidelberg.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by an increased number of platelets in the peripheral blood. Recently, somatic frameshift mutations at ex...

Chronic myeloid neoplasms have susceptibility to transform into acute myeloid leukemia due to attainment of additional molecular lesions. We here describe the kinetics of a del(7q) driven leukemogenesis in a patient with multiple TET2 mutations and JAK2 V617F mutated chronic myeloproliferative neoplasm. The del(7q) emerged in the accelerated phase of disease, which was preceded by a lag phase of almost three years with normalized peripheral blood cell counts. Our results reveal that the del(7q), independently of other lesions, acts as a leukemic driver in this patient and that the stable long-lasting normalization of peripheral blood cell values concealed pending transformation.

Several studies have shown that thrombotic events may underlie a latent or subclinical myeloproliferative neoplasm (MPN) and precede its definite diagnosis by 1–2 years. An early diagnosis of patients with MPN, especially those with thrombotic events in the latent MPN phase, would be beneficial for their management, preventing further morbidity and improving their quality of life. For the majority of these cases, the location of thrombosis is mainly in the splanchnic major veins, while ischemic stroke and cerebral venous thrombosis are rarely observed. In this report, we present a female patient with transient ischemic attacks who suffered from a latent MPN, on the basis of a positive testing for the JAK2-V617F mutation.

Background. In patients with Ph-negative chronic myeloproliferative neoplasm (MPN) the molecular pattern, beside other characteristics at diagnosis, has been related to the disease prognosis. Aim. To compare clinical and biological features at diagnosis and during the follow-up in gender/age-matched MPN patients showing different molecular pattern. Material and methods. The Registro Italiano Trombocitemie (RIT) is a web-based registry that includes thrombocythemic MPN patients diagnosed according to PVSG or WHO criteria, registered after 2005, and then prospectically followed. The JAK2 V617F mutation (JAK2+) was reported in 941 (58.4%) out of 1610 tested patients. On the basis of subsequent tests, performed in part of the JAK2 WT (JAK2-) subjects, 103 patients were JAK2-/CALR+ (CALR+), 14 patients were JAK2-/CALR-/MPL+ (MPL+), and 46 were JAK2-/CALR-/MPL- (3NEG). The 103 CALR+ patients were compared with 309 (103 x 3) JAK2+ patients matched for gender, age, and revised diagnosis (WHO 2008 criteria). A similar comparison was done between 46 3NEG patients and other 138 (46 x 3) JAK2+ matched patients. Results. CALR+ and matched JAK2+ patients had, as expected, the same gender distribution (males 41%), the same median age (51 years), and no significant difference (p 0.42) in the WHO diagnosis distribution. CALR+ patients, as compared with JAK2+ patients, showed at diagnosis: higher median platelet (PLT) count (839 vs 718 x109/L, p CARL+ and JAK2+ patients had the same rate of antiplatelet and cytoreductive treatment (96% vs 96%, and 86% vs 84%, respectively). During the follow-up the incidence of thrombotic and hemorrhagic events was not significantly different (1.3 vs 1.1/100 pt-years, and 1.0 vs 0.6/100 pt-years, respectively). Moreover, no significant difference was observed in the incidence of evolution to overt primary myelofibrosis (PMF, 0.76 vs 0.61/100 pt-years), polycythemia vera (PV, 0 vs 0.24/100 pt-years), and AL/MDS (0.08 vs 0.10/100 pt-years). Finally, the same overall survival was found after 5, 10. 15, and 20 years (99, 97, 94, 93%, respectively). 3NEG patients, as compared with JAK2+ matched patients, showed at diagnosis: lower median WBC count (7.9 vs 10.9 x 109/L, p 0.03); lower Hb and/or HCT level (p 0.006); lower rate of splenomegaly (7% vs 28%, p 0.003); lower rate of symptoms (35% vs 51%, p 0.049). No significant difference was found in: median PLT count (700 vs 720 x 109/L, p 0.61); PrTh (7% vs 16%, p 0.11); prior hemorrhage (4.7% vs 7.5%, p 0.52); high/intermediate thrombotic risk (IPSET, 36 vs 48%, p 0.37). Moreover, no significant difference was observed during the follow-up in: antiplatelet and cytoreductive treatment; thrombosis and hemorrhage rate; PMF, PV, and AL/MDS evolution; overall survival. Conclusion. CALR+ patients, as compared with JAK2+ matched patients, although showed a lower thrombotic risk (lower WBC and HCT levels, lower PrTh rate), received the same antiplatelet and cytoreductive treatment, had the same incidence of adverse events during the follow-up (vascular complications and disease evolution/transformation), and had the same overall survival. 3NEG patients, as compared with JAK2+ matched patients, showed results similar to those observed by comparing CALR+ and JAK2+ matched patients. To better define the role of the precise definition of molecular pattern in Ph-MPN patients, new prospective controlled studies seem necessary. Disclosures De Stefano: Janssen Cilag: Research Funding; Roche: Research Funding; Novartis: Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Bruno Farmaceutici: Research Funding; Celgene: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Shire: Speakers Bureau. Passamonti:Novartis: Consultancy, Honoraria, Speakers Bureau.