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Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P= .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.govas #NCT00514488.

Background: Dasatinib (DAS) is a 2ndgeneration (2ndgen) tyrosine kinase inhibitor (TKI) approved for 1stline treatment of chronic myeloid leukemia (CML) patients based on DASISION study results. Most data on 2ndgeneration TKIs are from company-sponsored studies, but the patient selection and the high rate of patient switching to other treatments may jeopardize data interpretation. Interestingly, despite significant differences in terms of cytogenetic and molecular response, 2ndgen TKIs did not produce relevant advantages in terms of overall survival (OS). A post-marketing surveillance in large independent trials is extremely important to confirm efficacy and the safety data.

In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications.

In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications.To evaluate in a large cohort of ET patients the potential relationship between the thrombosis history and the main clinical and biological characteristics at diagnosis, i.e. before any interference of cytoreductive treatment.A cohort of ET patients (PVSG or WHO criteria) of the Registro Italiano Trombocitemie (RIT) was retrospectively analyzed through logistic regression models.A total of 977 patients, 387 males and 590 females, presented at diagnosis: median age 56 y (43% with age >60 y), median PLT count 783 x 109/L (33% with low thrombocytosis, <700 x 109/L), median WBC count 8.8 x 109/L (29% with leukocytosis, >10 x 109/L), median HCT 42.6% (high HCT: >47% in 24% of the males and >44% in 23% of the females), CV general risk factors in 69% of cases (one of smoking, hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, obesity, CV disease, familiarity for thrombosis), bone marrow fibrosis grade 0 in 67% of cases, JAK2 V617F mutation in 56% of the 399 tested patients.The history of thrombosis (arterial in 74% of cases) was reported in 194 (19.9%) patients.The history of thrombosis in univariate analysis was significantly related to: age >60 y (p 0.001), male gender (p 0.009), CV general risk factors (p 0.002), low thrombocytosis (p 0.000), leukocytosis (p 0.003), high HCT (p 0.004), and JAK2 V617F mutation (p 0.008). No relationship was found with bone marrow fibrosis.In multivariate analysis a relationship was confirmed between thrombosis history and age >60 y (p 0.023), male gender (0.046), CV general risk factors (0.039), low thrombocytosis (p 0.004), leukocytosis (0.019), and JAK2 V617F mutation (p 0.033).The rate of thrombosis history in the patients without both low thrombocytosis and leukocytosis (11%, 49/428) resulted significantly lower (p 0.0001) than in the patients with leukocytosis (24%, 54/224), the patients with low thrombocytosis (27%, 71/266), and the patients with both low thrombocytosis and leukocytosis (34%, 20/59).In this cohort of ET patients the rate of thrombosis history in multivariate analysis is significantly related to various clinical and biological characteristics at diagnosis, including low thrombocytosis (PLT <700 x 109/L), leukocytosis (WBC >10 x 109/L), JAK2 V617F mutation, age >60 y, male gender, and CV general risk factors.this study was partially supported by the GIMEMA Foundation (Promotor of the RIT) and by the AIL Foundation.Gugliotta: SHIRE Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

No relevant conflicts of interest to declare.

Abstract 4454

In essential thrombocythemia (ET) patients history of thrombosis and age over 60 y are validated risk factors for thrombosis; the thrombocytosis is a constitutive abnormality associated with both thrombotic and hemorrhagic risk; JAK2 V617F mutation, leukocytosis, and male gender are candidate thrombotic risk factors.To evaluate in ET patients clinical-biological characteristics at diagnosis and their relationship with thrombosis occurrence before and after diagnosis.A cohort of ET patients of the Registro Italiano Trombocitemia (RIT) was retrospectively analysed. This preliminary report in detail considers data on thrombosis history.A total of 977 patients, 387 males and 590 females, presented at diagnosis: median age 55 y, median PLT count 783 × 109/L, median WBC count 8.8 × 109/L, median Hb 14.1 g/dL, bone marrow fibrosis (grade >0) in 33% of cases, history of thrombosis in 189 cases (19.3%). The patients at high risk (age over 60 y and/or history of thrombosis) were 511 (52 %). The thrombosis history in univariate analysis was significantly related to: age over 60 y (p 0.001), male gender (p 0.045), low thrombocytosis (PLT <783 x109/L, p 0.001), leukocytosis (WBC >8.8 x109/L, p 0.01), and JAK2 V617F mutation (p 0.006). No relationship was found with the bone marrow fibrosis.The 977 patients, when both PLT count and WBC count at diagnosis were considered, were subdivided in four groups: group 1: 202 pts with low thrombocytosis and leukocytosis; group 2: 270 pts with low thrombocytosis and no leukocytosis; group 3: 272 pts with high thrombocytosis and leukocytosis; group 4: 197 pts with high thrombocytosis and no leukocytosis. In those patients, the thrombosis history was: 26.7% in the group 1(both risk factors); 24.1% in the group 2 (PLT risk factor); 20.2% in the group 3 (WBC risk factor); 7.6% in the group 4 (no risk factors). The rate of thrombosis history in patients with one or two of these risk factors was significantly (p 0.001) higher than in patients with no risk factors. The thrombotic events during the follow up (4088 pt-y) are still object of analysis.In this cohort of ET patients the rate of thrombosis history in univariate analysis was related to age over 60 y. Moreover, a significant relationship was found with PLT count at diagnosis below the median value (783 x109/L), WBC count at diagnosis over the median value (8.8 x109/L), JAK2 V617F mutation, and male gender.No relevant conflicts of interest to declare.

Abstract 3836This icon denotes a clinically relevant abstract

Hematological and extra-hematological adverse events associated to Hydroxyurea (HU) treatment in patients with chronic myeloproliferative neoplasms (MPN) are object of particular interest in the Ph-negative MPN since they can significantly limit the HU use.To evaluate the extra-hematological adverse events associated to HU treayment in a large cohort of Essential Thrombocythemia (ET) patients.One thousand and seventy-five out of the 2005 ET patients registered in the RIT were treated with HU and are the object of this report. The patients, 641 females (59.6%) and 434 males (40.4%), diagnosed according to the PVSG or WHO criteria in 54 hematological centers of the RIT, started treatment with HU as first (92%) or second (8%) line, at median age of 65 years.The mean duration of HU treatment was 3.3 years. The HU treatment was withdrawn in 221 (20.5%) patients after a mean of 3.0 years.The administered dose of HU was 0.25–3.0 g/day (median 1), and a mean cumulative dose was 1113 g. The extra-hematological adverse events (EHAEs) observed during the HU treatment were distinguished in HU related AEs (HU-EHAEs), ET related AEs (ET-EHAEs) and HU or ET unrelated AEs (U-EHAEs).Results. During the HU treatment (3587 pt-y) 378 EHAEs were reported in 207 (19.3%) patients, being the HU-EHAEs 244 (6.8/100 pt-y) in 170 (15.8%) patients. In detail, the HU-EHAEs were: dermatological in 108 (48.3%) cases (38 hyperpigmentation, 26 leg ulcers, 22 maculo-papular rash, 10 lichenoid eruptions, 5 skin cancer, 4 alopecia); gastro-intestinal in 80 (32.8%) cases (37 nausea/vomiting, 30 diarrhea, 13 gastro-intestinal intolerance); systemic in 35 (14.3%) cases (28 fever, 7 fatigue); neurological in 19 (7.8%) cases (headache); miscellanea in 2 (0.8%) cases.This preliminary analysis in 1075 ET patients of the Registro Italiano Trombocitemia (RIT) treated with HU shows that the extra-hematological adverse events referred to the HU (HU-EHAEs) occurred with not negligible rate (6.8/100 pt-y) and need to be object of attention in the management of ET patients.No relevant conflicts of interest to declare.

Abstract 1973

The median age of an unselected population of Ph+ CML patients is close to 60 years. In the prognostic classifications (Sokal, Blood 1984; Hasford, JNCI 1998) that were elaborated before the introduction of IM, age was a significant and important prognostic factor. The most recent IM studies have not clarified the prognostic importance of age and IM therapy is still denied to several elderly patients.to asses the relationship between age (less and more than 65 years) and outcome, in CML patients treated front-line in early chronic phase (ECP).We analyzed the data of 559 previously untreated ECP patients who were assigned to receive IM 400 mg daily (76%) or 800 mg daily (24%) in three controlled, prospective studies of GIMEMA (Clin Trials Gov. NCT00514488 and NCT00510926; and an observational study of IM 400 mg). The median follow-up is currently 42 (extremes 1 – 64) months. There were 115 patients more than 65 years old (median age 71 years), while 444 (79%) were less than 65 years (median age 46 years). The proportion of patients who were treated with IM 800 mg daily was the same in both age groups.The cumulative complete cytogenetic and major molecular response rates were identical in the two age groups (88% vs 88% and 82% vs 83%, respectively). However, overall survival (86% vs 93%, p = 0.01), failure-free survival (72% vs 81%, p=0.03) and particularly event-free survival (calculated based on the intention-to-treat principle, where events were any failure [according to the European LeukemiaNet criteria – Baccarani, Blood 2006] and treatment discontinuation for any cause) (60% vs 71%, p=0.006) were significantly inferior in the older age group. All these difference were mainly due to comorbidities leading to more deaths in CP (table).These data show that response to IM was not affected by old age. Survival curves were affected because of age-related complications and comorbidities. Age should never be a contraindication to IM treatment. Acknowledgments: European LeukemiaNet, COFIN, University of Bologna and BolognAIL.Saglio: Novartis: Honoraria. Baccarani:Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Mayer Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Abstract 1118

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<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<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<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<0.001) and for HU (from 64 to 69 yrs, p<0.001) while it decreased for IFN (from 49 to 46 yrs, p<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.

Sokal risk formulation was elaborated 25 years ago, based on very simple factors (age, spleen size, platelet count, and percentage of myeloblasts in the peripheral blood), based on patients treated with conventional chemotherapy. In spite of that, Sokal risk score is still the major prognostic factor for response to treatment with the tyrosine kinase inhibitor, Imatinib mesylate (IM). Since several preclinical, pharmacokinetic and clinical studies suggested that the therapeutic efficacy of IM may be concentration/dose–dependent, we assigned prospectively 217 adult patients with Ph pos CML, Sokal high risk (SHR), to be treated front line with IM 400 mg or 800 mg (Clin.Trials Gov. NCT00514488), comparing the cytogenetic and the molecular response rates at 3, 6, and 12 months. Cytogenetic response was evaluated by chromosome banding analysis (CBA) of marrow metaphases, and by FISH analysis of marrow cells in case of insufficient metaphase number. Molecular response was evaluated by RT-Q-PCR (PB), according to the international scale. The results are shown in Table 1. No difference between the two arms was significant at any time point. In the 400 mg arm, the median daily dose of IM was 400 mg, with 87% of patients receiving 350 to 400 mg. In the 800 mg arm, the median daily dose of IM was 720 mg, with 63% of patients receiving 600 to 800 mg. The CCgR rate was 86%, vs 66% in the patients who received a median daily dose of 600 to 800 or less than 600 mg daily, respectively (p=0.013). With a median follow up of 31 months (range 1–49 months), progression-free and overall survival are higher than 90% in both arms. Based on an intention-to-treat analysis, this study did not show a significant benefit of 800 mg over 400 mg in SHR patients, but the patients who could comply with the high dose had a better cytogenetic outcome. 3 months 6 months 12 months 400 800 400 800 400 800 (1)Refusal, or lost to follow-up, or protocol violations (2)Failure was defined according to the ELN recommendations (Baccarani et al, Blood2006;108:1809–1920) (3)No Ph pos metaphases out of at least 20 marrow cell metaphases, by CBA, or < 1% BCR-ABL positivity out of at least 200 marrow cells, by FISH (4)BCR-ABL:ABL < 0.10 and < 0.005 by RT-Q-PCR, converted to the International Scale. No. of pts 109 108 109 108 109 108 Dropouts(1) 4% 4% 5% 7% 5% 8% D/C adverse events 1% 2% 4% 4% 4% 7% Failure(2) 1% 1% 9% 10% 16% 15% CCgR(3) 19% 25% 49% 52% 58% 64% MolR>3.0 log(4) 7% 12% 25% 31% 33% 40% MolR>4.5 log(4) 1% 2% 3% 9% 10% 19% Transcript level (median) 2.085 1.122 0.378 0.108 0.084 0.036 Table 1: Summary of cytogenetic and molecular results. All percentages are calculated based on all randomized patients, according to the intention-to-treat principle. p-values are > 0.10 for all comparisons.

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.

Sokal risk formulation was elaborated 25 years ago, based on very simple factors (age, spleen size, platelet count, and percentage of myeloblasts in the peripheral blood), based on patients treated with conventional chemotherapy. In spite of that, Sokal risk score is still the major prognostic factor for response to treatment with the tyrosine kinase inhibitor, Imatinib mesylate (IM). Since several preclinical, pharmacokinetic and clinical studies suggested that the therapeutic efficacy of IM may be concentration/dose–dependent, we assigned prospectively 217 adult patients with Ph pos CML, Sokal high risk (SHR), to be treated front line with IM 400 mg or 800 mg (Clin.Trials Gov. NCT00514488), comparing the cytogenetic and the molecular response rates at 3, 6, and 12 months. Cytogenetic response was evaluated by chromosome banding analysis (CBA) of marrow metaphases, and by FISH analysis of marrow cells in case of insufficient metaphase number. Molecular response was evaluated by RT-Q-PCR (PB), according to the international scale. The results are shown in Table 1. No difference between the two arms was significant at any time point. In the 400 mg arm, the median daily dose of IM was 400 mg, with 87% of patients receiving 350 to 400 mg. In the 800 mg arm, the median daily dose of IM was 720 mg, with 63% of patients receiving 600 to 800 mg. The CCgR rate was 86%, vs 66% in the patients who received a median daily dose of 600 to 800 or less than 600 mg daily, respectively (p=0.013). With a median follow up of 31 months (range 1–49 months), progression-free and overall survival are higher than 90% in both arms. Based on an intention-to-treat analysis, this study did not show a significant benefit of 800 mg over 400 mg in SHR patients, but the patients who could comply with the high dose had a better cytogenetic outcome.

Background The outcome of 129 pregnancies, in 97 women with ET diagnosed in seventeen Italian hematological centres from June 1998 to July 2007, were retrospectively analyzed by the RIT. Diagnosis was made according to criteria (PVSG or WHO) in use at the time of first observation. The median age was 27 years (range 17–45) at ET diagnosis and 32.5 years (range 21–45) at the beginning of the pregnancy. The diagnosis of ET was established in 87 patients before the first pregnancy (median interval 27 months, range 1–96), in 9 patients during a pregnancy and in one patient during an in vitro fertilization treatment. JAK2 (V617F) mutation was documented in 16 out of the 33 women studied till now. Platelet count ranged from 489 to 2,140 × 109/L (median 867) at diagnosis, and from 232 to 2,000 × 109/L (median 564) at delivery. Results: Only 120 out of the 129 pregnancies are valuable (six voluntary abortions and three ongoing pregnancies are not considered).The pregnancies outcome was: live birth in 90 cases (75%), spontaneous abortion in 26 cases (22%) (19 in the first trimester and 7 in the second trimester), still-birth in 4 cases (3%). Twelve (10%) premature births were reported, and two pregnancies ending in live birth were complicated by eclampsia or pre-eclampsia. The foetal growth was within normal limits in 76 out of the 78 full term births. The delivery was by caesarean section in 40% of cases. Thirty-six pregnancies (30%) occurred during cytoreductive treatment, but the outcome was not different than in the other ET patients (p 0.49). Aspirin treatment (mainly 100 mg/ day) was reported in 92 pregnancies (76.6%), associated in 18 cases to prophylactic LMWH during the last week before delivery and six weeks post-partum. The rate of successful pregnancy in the group receiving ASA was not different respect to the group not receiving ASA (p 0.62,). JAK2 mutation was not significantly (p 0.08) associated with a higher risk of foetal loss, but the analysis has to be completed since the study is still ongoing. The IFN treatment (as single agent or combined with ASA) was performed in 21 high-risk pregnancies. Nineteen of these pregnancies were valuable (1 ongoing and 1 elective abortion): 18 pregnancies (95%) ended in live births, and this outcome was significantly better than in patients not receiving IFN (p 0.04). Conclusion This retrospective study shows that in ET women: the IFN therapy seems able to protect against fetal loss; low-dose aspirin has not a statistically significant favourable impact on the pregnancy outcome; the unfavourable effect of JAK2 mutation could be confirmed after completion of the study. A prospective study has been recently activated by the RIT (GIMEMA project), with aim to improve the diagnostic and therapeutic approach of pregnant ET.

Background The outcome of 129 pregnancies, in 97 women with ET diagnosed in seventeen Italian hematological centres from June 1998 to July 2007, were retrospectively analyzed by the RIT. Diagnosis was made according to criteria (PVSG or WHO) in use at the time of first observation. The median age was 27 years (range 17–45) at ET diagnosis and 32.5 years (range 21–45) at the beginning of the pregnancy. The diagnosis of ET was established in 87 patients before the first pregnancy (median interval 27 months, range 1–96), in 9 patients during a pregnancy and in one patient during an in vitro fertilization treatment. JAK2 (V617F) mutation was documented in 16 out of the 33 women studied till now. Platelet count ranged from 489 to 2,140 × 109/L (median 867) at diagnosis, and from 232 to 2,000 × 109/L (median 564) at delivery.

Epidemiological, diagnostic, prognostic and therapeutical data were retrospectively obtained by the Italian Registry in over 2000 Essential Thrombocythemia (ET) patients who mainly were diagnosed according to the PVSG criteria and were treated with potentially leukemogenic drugs. The Registro Italiano Trombocitemie (RIT), that is a GIMEMA project, has been activated in order to registry italian ET patients, to improve the diagnosis appropriateness (WHO criteria), to promote the acquisition of biological data, to evaluate the compliance to the therapeutical guidelines of the Italian Society of Hematology (SIE), to monitor in particular the ET patients receiving Interferons alpha and Anagrelide, to evaluate cases of pregnancy, pediatric age and familiarity, to define the prognostic value of the biological factors as JAK2 mutation, clonality, etc, to create a network for activation of new clinical and biological studies. The RIT, co-ordinated by the Hematology Unit of Reggio Emilia, is a web based registry that beside a public area comprehends a database of italian ET patients. The data, with respect of the privacy rules, are object of validation and analysis by various RIT expert subcommittees. Eighty hematological Institutions adhered to the RIT and 801 patients have been registered since June 2005. The ET diagnosis was done according to the PVSG (90%) and WHO (10%) criteria. The patients, 492 females and 309 males, had age <40 yr (19%), 40–60 yr (32%), 60–70 yr (19%), >70 yr (30%), and the median age was 59 years. At diagnosis the platelet count was >1000 ×109/L in 29% of cases (mean 932). Few patients had prior thrombosis (4%; major 2%) and prior hemorrhage (2.6%). Patients at high risk of thrombosis were 55% on considering age >60 yr and/or previous thrombosis and/or PLT count >1500 ×109/L, and 65% on considering the PLT count cut-off of 1000 ×109/L. The patients shown general thrombotic risk factors (70%), disease related symptoms (40%) and splenomegaly (25%). By applying the WHO diagnostic criteria, the picture of true ET was found in 27% of cases. Sixty pregnancies have been reported. Aspirin was administered in 72% of patients and cytoreduction was performed in 62% of them, with use of Hydroxyurea (65%), Anagrelide (10%), Interferons alpha (10%), Pipobroman (4%), Busulfan (2%). A separate analysis for patients treated with Anagrelide and Iterferons alpha is in progress. To improve the diagnostic approach, the RIT has promoted the bone marrow biopsy revision (WHO criteria) and the acquisition of the new biological parameters.

Epidemiological, diagnostic, prognostic and therapeutical data were retrospectively obtained by the Italian Registry in over 2000 Essential Thrombocythemia (ET) patients who mainly were diagnosed according to the PVSG criteria and were treated with potentially leukemogenic drugs. The Registro Italiano Trombocitemie (RIT), that is a GIMEMA project, has been activated in order to registry italian ET patients, to improve the diagnosis appropriateness (WHO criteria), to promote the acquisition of biological data, to evaluate the compliance to the therapeutical guidelines of the Italian Society of Hematology (SIE), to monitor in particular the ET patients receiving Interferons alpha and Anagrelide, to evaluate cases of pregnancy, pediatric age and familiarity, to define the prognostic value of the biological factors as JAK2 mutation, clonality, etc, to create a network for activation of new clinical and biological studies. The RIT, co-ordinated by the Hematology Unit of Reggio Emilia, is a web based registry that beside a public area comprehends a database of italian ET patients. The data, with respect of the privacy rules, are object of validation and analysis by various RIT expert subcommittees. Eighty hematological Institutions adhered to the RIT and 801 patients have been registered since June 2005. The ET diagnosis was done according to the PVSG (90%) and WHO (10%) criteria. The patients, 492 females and 309 males, had age <40 yr (19%), 40–60 yr (32%), 60–70 yr (19%), >70 yr (30%), and the median age was 59 years. At diagnosis the platelet count was >1000 ×109/L in 29% of cases (mean 932). Few patients had prior thrombosis (4%; major 2%) and prior hemorrhage (2.6%). Patients at high risk of thrombosis were 55% on considering age >60 yr and/or previous thrombosis and/or PLT count >1500 ×109/L, and 65% on considering the PLT count cut-off of 1000 ×109/L. The patients shown general thrombotic risk factors (70%), disease related symptoms (40%) and splenomegaly (25%). By applying the WHO diagnostic criteria, the picture of true ET was found in 27% of cases. Sixty pregnancies have been reported. Aspirin was administered in 72% of patients and cytoreduction was performed in 62% of them, with use of Hydroxyurea (65%), Anagrelide (10%), Interferons alpha (10%), Pipobroman (4%), Busulfan (2%). A separate analysis for patients treated with Anagrelide and Iterferons alpha is in progress. To improve the diagnostic approach, the RIT has promoted the bone marrow biopsy revision (WHO criteria) and the acquisition of the new biological parameters.