Simonetta Pardini

Effect of rituximab on clinical and laboratory features of antiphospholipid syndrome: a case report and a review of literature:

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by a hypercoagulable state related to persistently elevated levels of antiphospholipid antibodies (aPL). Current treatment for APS is only partially effective and new therapies are strongly needed. We report on a case of a 50 years old man with APS who suffered from recurrent thromboembolic episodes despite conventional anticoagulant treatment. Eight years after the first thrombotic manifestation he was diagnosed with a large B cell non-Hodgkin lymphoma. Treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) plus rituximab was started with partial clinical remission of lymphoma and normalization of aPL levels with a three years follow-up period free of thrombotic episodes. A review of the literature revealed that only 12 case reports on the use of rituximab in patients with primary, secondary and catastrophic APS have been published. Current knowledge clearly suggests the need for clinical trials to evaluate the effect of rituximab in the treatment of resistant APS. Lupus (2008) 17, 50—55.

Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study

Background:Optimal adherence to imatinib therapy is of paramount importance to maximise treatment effectiveness in patients with chronic myeloid leukaemia (CML). The main objective of this study was to investigate patient-reported personal factors associated with adherence behaviour.Methods:Analysis was conducted on 413 CML patients receiving long-term therapy with imatinib. Adherence behaviour was measured with the Morisky Medication Adherence Scale and personal factors investigated included: quality of life, perceived social support, fatigue, symptom burden, psychological wellbeing and desire for additional information. Key socio-demographic and treatment-related factors were also taken into account. Univariate and multivariate logistic regression analyses were used to investigate factors associated with optimal adherence to therapy.Results:In all, 53% of patients reported an optimal adherence behaviour. The final multivariate model retained the following variables as independent predictors of optimal adherence to therapy: desire for more information (ref. no), odds ratio (OR)=0.43 (95% confidence interval (CI), 0.29–0.66; P<0.001), social support (higher score representing greater support), OR=1.29 (95% CI, 1.11–1.49; P<0.001) and concomitant drug burden (ref. no), OR=1.82 (95% CI, 1.18–2.80; P=0.006).Conclusion:This study suggests that a higher level of social support, satisfaction with information received and concomitant drug burden are the main factors associated with greater adherence to long-term imatinib therapy.

ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization

Inherited thrombocytopenias (ITs) are a heterogeneous group of syndromic and nonsyndromic diseases caused by mutations affecting different genes. Alterations of ACTN1, the gene encoding for α-actinin 1, have recently been identified in a few families as being responsible for a mild form of IT (ACTN1-related thrombocytopenia; ACTN1-RT). To better characterize this disease, we screened ACTN1 in 128 probands and found 10 (8 novel) missense heterozygous variants in 11 families. Combining bioinformatics, segregation, and functional studies, we demonstrated that all but 1 amino acid substitution had deleterious effects. The clinical and laboratory findings of 31 affected individuals confirmed that ACTN1-RT is a mild macrothrombocytopenia with low risk for bleeding. Low reticulated platelet counts and only slightly increased serum thrombopoietin levels indicated that the latest phases of megakaryopoiesis were affected. Given its relatively high frequency in our cohort (4.2%), ACTN1-RT has to be taken into consideration in the differential diagnosis of ITs.

Serum erythropoietin levels in thalassemia intermedia

SummarySerum concentrations of erythropoietin (EPO) were determined by immunoassay in 45 patients with thalassemia intermedia (TI). The mean serum level of EPO was significantly higher in the thalassemic patients than in the controls, but transfused subjects had lower pretransfusional serum concentrations of EPO than untransfused ones. An inverse relationship between the serum values of EPO and total hemoglobin was observed only in the untransfused thalassemic patients. These data suggest that in TI, even a low transfusional regimen may cause a decrease in serum concentration of EPO, independent of the level of total Hb.

A case of coexistence between JAK2V617F and BCR /ABL.

Very recently the JAK2V617F mutation has been described in BCR⁄ABL+ patients for the first time. Even though characterized by very different clinical patterns, these cases raise some questions about the biological meaning of the coexistence between these disease-specific molecular markers. The present report confirms that the unexpected coexistence between these two disease-specific molecular markers - the JAK2V617F mutation and the BCR⁄ABL translocation - is possible.

A 12‐year preventive program for β‐thalassemia in Northern Sardinia

From 1980 to 1991, 6.3% of the adult population of the province of Sassari, Northern Sardinia, underwent voluntary β‐thalassemia screening. Of the 28 000 subjects examined, 15.7% proved to be heterozygotes for β‐thalassemia. In addition, the screening of 7500 students in 26 villages in Sassari province fixed the frequency of β‐thalassemia in this part of Sardinia at 10.4%. Of the 539 couples at risk to be expected from this figure, the screening detected 43% (234). The data suggest that inductive screening played a major role in the efficiency of this preventive β‐thalassemia program. Follow up of 221 pregnancies found to be at risk for homozygous β‐thalassemia and referred to the Antenatal Diagnosis Service, Cagliari, Southern Sardinia, showed that antenatal diagnosis was carried out in 80% of them. The overall percentage of couples refusing antenatal diagnosis was 10.8%, but over the years the acceptance rate for the procedure increased from 87% to 96%. Atypical hematological findings in 1.5% of 468 members of the couples at risk required globin chain synthesis and molecular analyses to define the precise β‐thalassemia genotype. Heterogeneous “mild”β‐thalassemia mutations as well as coexisting δ‐thalassemia were found in silent type I and type II β‐thalassemia carriers which, without chain synthesis and DNA investigations, would have escaped detection.

Dramatic erythroid response to low-dose thalidomide in two patients with transfusion independent thalassemia and severe post-transfusional alloimmune hemolysis

versus conventional care regimens in olders patients with newly diagnosed acute myeloid leukemia. EHA Annual Meeting Abstracts 2014:LB-6212. 11. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012;30:2670–2677. 12. Cashen AF, Schiller GJ, O’Donnell MR, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 2010;28:556– 561. 13. Lubbert M, Ruter BH, Claus R, et al. A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy. Haematologica 2012;97:393–401. 14. Ritchie EK, Feldman EJ, Christos PJ, et al. Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia. Leuk Lymphoma 2013;54:2003–2007.

Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era

Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty‐seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow‐up, the BCR‐ABL transcripts level was available in 96/101 living patients (95%) The BCR‐ABL:ABL ratio was between 0.1 and 0.01% (MR3.0) in 17%, and less than 0.01% (MR4.0) in 81% of patients. No patient was completely molecular negative (MR4.5 or MR5.0). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR4.0. Complete molecular response (MR4.5 or MR5.0) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα. Am. J. Hematol. 89:119–124, 2014.

Hematological and Biosynthetic Features of β°-Thalassemia with an Associated α-Thalassemia Heterozygosity in Sardinia

Total hemoglobin, PCV, hemoglobin A 2 and hemoglobin F were determined in controls, β 0 -thal heterozygotes and α-thal + β thal heterozygotes. Also the distribution of mean corpuscular volume and the mean corpuscular hemoglobin values in Sardinian β 0 -thal heterozygotes with and without an associated α-thal and the ratio of α/β chain synthesis in β 0 -thal heterozygotes with or without an associated α-thal were studied.

Is there a role for imatinib mesylate in the treatment of eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic eosinophilic vasculitis, belonging to the group of ANCA-associated vasculitides (AAV). EGPA pathogenesis is still elusive, but a potential role for IL-5 and Eotaxins mediated eosinophil activation has been reported. Imatinib mesylate, a tyrosine kinase (TK) inhibitor, is approved for the treatment of chronic myeloid leukaemia and FIP1L1/PDGFRA positive gene fusion hypereosinophilia. A potential role for imatinib in the treatment of idiopathic hypereosinophilic syndrome (HES) and AAV has been recently proposed.