Vincenzo Accurso

Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

BackgroundHydroxyurea (HU) is a commonly used first‐line treatment in patients with polycythemia vera (PV). However, approximately 15%–24% of PV patients report intolerance and resistance to HU.MethodsThis phase IV, European, real‐world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24‐month follow‐up. The primary objective was to describe the profile and disease burden of PV patients.ResultsIn the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment‐related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths,...

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

Twenty-four patients with immune thrombocytopenic purpura (ITP) were treated with high doses of intravenous immunoglobulin (Ig). Increase in platelets was observed in all the patients. The maximum value was reached between the seventh and the twelfth day of treatment. The mean number of platelets was 18 x 10(9)/l before the treatment and 150 x 10(9)/l after the treatment. The effect was transient; in fact, a fall in the platelets was observed after 18 days of treatment. Our study confirms that high doses Ig is an effective treatment of ITP, but the high cost and the temporary effect limit its use only in those cases in which other treatments are ineffective or contraindicated.

Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

Twenty patients with various stages of RA were examined. They included: 1) 7 cases in Steinbroker stage 1 (onset); 2) 13 cases in Steinbroker stage 2-3 (chronic). The group was divided into 16 treated and 4 untreated cases. Monoclonal antibodies were used to assay T3, T4, T8 and T4/T8 ratio and the results were compared with those in a control group. The results showed a T8 deficit and a consequent change in the T4/T8 ratio in untreated subjects with "onset" RA. The immune situation of the chronic and treated cases was very similar to that in the control group probably as a result of treatment.

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases describing TBC reactivations in MF patients assuming ruxolitinib and successfully treated with 4-drug anti-TBC therapy are available in the literature to date. The case we reported describes an isolated lymph nodal TBC reactivation in a patient with the diagnosis of post-essential thrombocythemia-MF during ruxolitinib treatment after a long course of interferon-a (IFN-α2b) assumed for the previous diagnosis of ET. The case we report teaches that lymphadenopathy with or without constitutional symptoms developing during ruxolitinib therapy should be considered as a possible manifestation of a TBC reactivation in patients with a previous positive TBC-exposure test. In these cases, Ziel-Nielsen testing on urine and sputum has to be performed to rule out infectiousness and eventually isolate the patient. Moreover, previous long-time exposition to IFN-α2b may be related with a higher risk for TBC reactivation in these subset of patients. We encourage reevaluation of the cohorts of patients treated with ruxolitinib in previous and current large prospective studies to study the possible correlation between previous exposition to IFN-α2b and TBC reactivation.

Ponatinib, an oral tyrosine kinase inhibitor with potent activity against native and mutant BCR-ABL1, is approved for patients with refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated, or for patients with the T315I mutation. Aim The aim of study was to assess real life efficacy and safety of ponatinib in a retrospective analysis of 49 patients with resistant/refractory CML from 9 Italian Hematological Institution. Results : At baseline, median age was 55 years and median time since diagnosis was 4,4 years; BCR-ABL1 kinase domain mutations were reported in 30,6 % of patients, with T315I only in 4 (26,6%) patients. The majority of Patients were heavily pretreated, with 26,5% having received 2 prior TKIs and 46,9% having received ≥3 prior TKIs; 28,2 % of patients were in 2 nd line treatment due to resistance. At Ponatinb start, 42 patients were in chronic phase, 4 in accelerate phase and 3 in blastic phase. 18 pts showed comorbidities, no cardiovascular and/or cerebrovascular eventswere present at diagnosis and before starting Ponatinib. Baseline cardiovascular risk factors for all patients were Diabetes 3/18, hypertension 12/18, hypercholesterolemia 1/18; general history of cardiovascular disease,( not ischemic) was reported in 3/18 patients at baseline. Concomitant medications were: Antihypertensives in 12/18, aspirin in 1/18, antidiabetes agents in 3/18, lipid-modifying agents in 1/18. The 91,8% patients performed cardiovascular evaluation before starting treatment resulting in normal cardiovascular function in the majority of them. Abnormalities were present in only 4 pts: one lower ejection fraction, one pericardic effusion and two hypertensive cardiomyopathies. The initial dose was 45 mg/day in 24 (48,9%), 30 mg/day in 16 pts (32,6%) and 15 mg/day in 9 pts (18,3%). 31 out of 49 patients obtained a response to Ponatinib. The cumulative response rates was: major cytogenetic response (MCyR), 4%; complete cytogenetic response (CCyR), 59.1%; molecular response 32,6% (major molecular response (MMR) 12,2%; Deep MR (MR4, MR 4.5, MR5) 20,4%. Characteristics of response to Ponatinib therapy are reported in table 1. Interestingly, almost all molecular responder patients maintained Ponatinib response. At the time of analysis, 36 patients are still on therapy. Ponatinib was discontinued in5 of the 31 responders patients due to side effects (n= 2), death (n=2), lost to follow-up (n=1). The side effects reported were vascular CNS stoke and back pain with bad compliance. The two deaths occurred after bone marrow transplantation in one patient and for causes not disease related for the other. Dose reduction was performed in 11 out of 31 responder patients because side effects (n=8: 5 dermatological, 1 atrial fibrillation, 1 hematological, 1hypertension ) or optimal response (n=3 ). The adverse events were reported in 21 of 49 patients. Non hematological side effects were: 9 dermatological, and 2 arthralgia , 1 patients developed diabetes, 2 patients ipercolesterolemia; 5 patients had hematological side effects (1 piastrinopenia, 3 pancitopenia, 1 MDS with trysomy 8). About cardiovascular events, only 5 patients showed these effects (1 atrial fibrillation, 3 hypertension, 1carotid thrombosis, 1 ischemic cardiopathy ), no one severe. CONCLUSION As in 5-yr long term results of PACE trial, also in our real life retrospective analysis, Ponatinib continues to show deep, lasting response in heavily-pretreated pts with CP-CML. In our analysis, almost all patients who obtained the molecular response, maintained it during the treatment, despite dose reduction, which should be associated to improved survival, also in a heavily-pretreated pts. Disclosures Specchia: Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Pane: Novartis: Honoraria, Speakers Bureau.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of Von Willebrand factor (VWF). Bleeding from the gastrointestinal (GI) tract is not uncommon in VWD and is usually associated with angiodysplasia. We report herein on the management of a patient affected by VWD2B with severe GI bleeding secondary to gastrointestinal stromal tumor (GIST) complicated by deep vein thrombosis (DVT). The current case demonstrated that the hemostatic balance, in RBDs under specific circumstances, can range from a tendency toward a hemorrhagic to normal or prothrombotic state. In these patients, a close collaboration between hematologists and surgeons can guarantee appropriate management in high-risk clinical scenarios.

Fourteen AIDS patients with constitutional symptoms without a known etiology were treated with intravenous immunoglobulins (IVIG). The dosage regimen was 300 mg/kg per day three times weekly for two weeks followed by 300 mg/kg per day once weekly for ten weeks. All patients improved clinically after treatment with IVIG. The reason for the clinical improvement in our cases is as yet unclear, but it is possible that immunoglobulins have had a therapeutic effect on the underlying immunologic disturbance.

Introduction Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by the increased red cell mass and high thrombotic risk. The main objective of therapy is to maintain the hematocrit <45% with hydroxyurea (HU) being the most common drug employed in first line. Patients developing resistance/intolerance to HU are at higher risk of thrombosis due to inadequate hematocrit control. Methods This ongoing phase 4 observational study recruited 352 patients with PV resistant and/or intolerant to HU treated with ruxolitinib (RUX), with a follow-up of 24 months after treatment initiation. In the present interim analysis, 150 patients with PV receiving RUX treatment for 52 weeks were evaluated for efficacy and safety parameters. Inclusion criteria were adult patients aged ≥18 years diagnosed with PV resistant/intolerant to HU (as per European LeukemiaNet [ELN] criteria) treated with RUX according to the approved local label. RUX treatment could be initiated up to 6 months be...

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

Since the beginning of HIV epidemic, it became clear that the modality of transmission was different between Western Countries and Africa (1). Infact, in Africa heterosexual contact is the most important factor in the spread of HIV infection and female prostitutes are considered to be the major reservoir of HIVinfection (2).

With this letter, we do ask the scientific community to take a clear position and make itself heard with a stentorian voice to protect public health from ethical misconduct. This renewal would lead not only to direct benefits to the research but also to the public image of the whole scientific world, thanks to a novel, more transparent, efficient, and effective procedure of academic publication. Alongside this, the goal is also to decrease the number of infodemic publications circulating in and out of the scientific community, especially if they concern health-sensitive topics like new drugs and vaccines.

Ponatinib, an oral tyrosine kinase inhibitor with potent activity against native and mutant BCR-ABL1, is approved for patients with refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated, or for patients with the T315I mutation. Aim The aim of study was to assess real life efficacy and safety of ponatinib in a retrospective analysis of 49 patients with resistant/refractory CML from 9 Italian Hematological Institution. Results : At baseline, median age was 55 years and median time since diagnosis was 4,4 years; BCR-ABL1 kinase domain mutations were reported in 30,6 % of patients, with T315I only in 4 (26,6%) patients. The majority of Patients were heavily pretreated, with 26,5% having received 2 prior TKIs and 46,9% having received ≥3 prior TKIs; 28,2 % of patients were in 2 nd line treatment due to resistance. At Ponatinb start, 42 patients were in chr...

Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed. Triple-negative patients had a significantly lower symptom load and a lower frequency of splenomegaly at diagnosis. The results show that the rate of thrombosis was equal in the two subgroups. Overall survival was slightly better in the triple-negative group of patients.

Infradiaphragmatic Hodgkin's disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of this condition. A series of 282 patients with CS I-II Hodgkin's disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups. The BDHD group was older (p < 0.0002), had a higher frequency of males (p < 0.08) and a different histological subtype group distribution (p < 0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p < 0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with AD...