Sara Marietti

The role of HLA-G 14-bp polymorphism in allo-HSCT after short-term course MTX for GvHD prophylaxis.

HLA-G molecules are HLA class Ib antigens characterized by tolerogenic and immunoinhibitory functions. The HLA-G 14-bp insertion/deletion (ins/del) polymorphism controls protein expression and seems to be implicated in both MTX treatment response and SCT outcome. The aim of our study is to evaluate the role of HLA-G 14 bp polymorphism in subjects affected by hematological malignancies undergoing allo-SCT and receiving MTX therapy for GvHD prophylaxis. We performed a retrospective analysis of HLA-G 14 bp polymorphism using a specific PCR in 47 recipients and in their respective donors, and evaluated the correlation with the incidence of aGvHD, OS and disease-free survival (DFS) after allo-SCT. We did not observe any correlation between this polymorphism and the risk of aGvHD occurrence. On the contrary, we found that the recipients with a 14 bp ins/14 bp ins genotype were characterized by a lower OS and DFS in univariate and multivariate analysis (OS=OR: 3.235; DFS=OR: 3.302). These data indicate a role for recipient HLA-G 14 bp polymorphism in allo-SCT immunotolerance status and follow-up.

The proliferative response to CpG-ODN stimulation predicts PFS, TTT and OS in patients with chronic lymphocytic leukemia

We recently reported that leukemic cells from IgVH-unmutated/progressive CLL more frequently proliferate in response to CpG-ODN stimulation than their corresponding counterparts. Here we evaluated the prognostic impact of this proliferative response in 91 CLL patients. The proliferative response was highly predictive of PFS, TTT and OS in the whole series and refined prognosis in patients with M-CLL. BCR stimulation modulated the response to CpG-ODN, suggesting that the proliferative capacity of the leukemic cells is related to antigen-encounter history. These data support the hypothesis that the capacity of the leukemic cells to respond to external stimuli influences disease progression in CLL.

Report of a novel kindred with antithrombin heparin-binding site variant (47 Arg to His) : Demand for an automated progressive antithrombin assay to detect molecular variants with low thrombotic risk

Report of a novel kindred with antithrombin heparin-binding site variant (47 Arg to His): Demand for an automated progressive antithrombin assay to detect molecular variants with low thrombotic risk -

CHLORAMBUCIL PLUS RITUXIMAB AS FRONT-LINE THERAPY IN ELDERLY/UNFIT PATIENTS AFFECTED BY B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A SINGLE-CENTRE EXPERIENCE.

The current standard first line therapy for fit patients with B-CLL/SLL is based on combination of fludarabine-cyclophosphamide and rituximab. However, elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl) only. However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3–4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3–4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL.

Eradication of JAK2 V617F mutation after allogeneic transplantation in a patient with myelofibrosis with myeloid metaplasia

Eradication of JAK2 V617F mutation after allogeneic transplantation in a patient with myelofibrosis with myeloid metaplasia

Role of flow-cytometric immunophenotyping in prediction of BCR/ABL1 gene rearrangement in adult B-cell acute lymphoblastic leukemia: FLOW-CYTOMETRY IN BCR/ABL1 ADULT B-ALL

We performed a retrospective analysis of 88 adult patients with B‐ALL diagnosed in our center by a flow‐cytometric assessment. Immunophenotypic expression of leukemic cells was explored by simultaneous evaluation of positivity, percentage of expressing cells and median fluorescence intensity (MFI). BCR/ABL1 fusion transcripts were assessed by RT‐PCR analysis and were identified in 36 patients (40.9%). CD10 and CD34 were positive in the totality of BCR/ABL1‐positive cases. Patients with gene rearrangement had a greater frequency of CD66c, CD13 and CD33 positivity compared with BCR/ABL1‐negative cases. Moreover, BCR/ABL1‐positive cases exhibited a greater median percentage and MFI values of CD13, CD33, CD66c, CD10, CD34 and CD25 expressions, but a lower median percentage and MFI values of CD38 and CD22 expressions than patients without gene rearrangement. Multivariate logistic regression analysis showed that CD10, CD38 and CD13 expressions were independent predictors for the presence of BCR/ABL1 rearrangement. Predictive probabilities of molecular occurrence based on these markers are proposed.

Extreme thrombocytosis in chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Th rombocytosis is a common feature in chronic myeloproliferative diseases, and contributes to an increased incidence of thrombotic and hemorrhagic events during the course of the disease. In chronic myeloid leukemia (CML), however, hemorrhagic and thrombotic complications, even with marked thrombocytosis, are rare (3% and 1%, respectively) [1]. Th e incidence of thrombocytosis in CML is reported to be around 30 – 50%. Extreme thrombocytosis, defi ned as

The use of low-dose alemtuzumab in pretreated B-cell chronic lymphocytic leukemia

Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007; 109: 3489–3495. 13 Xiong W, Wu X, Starnes S, Johnson SK, Haessler J, Wang S et al. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood 2008; 112: 4235–4246. 14 Rachel JM, Zucker ML, Fox CM, Plapp FV, Menitove JE, Abbasi F et al. Monoclonal B-cell lymphocytosis in blood donors. Br J Haematol 2007; 139: 832–836.

Long-term follow up of frontline therapy with fludarabine and cyclophosphamide in chronic lymphocytic leukemia: impact of biological parameters on clinical outcome

Dear Editor, Recent advances in the biology of chronic lymphocytic leukemia (CLL) revolutionized our understanding of the disease and opened place to risk-adapted treatment. While the gold standard therapy in fit patients is still fludarabine, cyclophosphamide, and rituximab (FCR), large subset of CLL patients is unable to complete the planned treatment because of excessive toxicity associated with elderly age and comorbidity [1–3]. Moreover, FCR regimen did not offer an improvement in terms of OR rate respect to fludarabine and cyclophosphamide (FC) in patients with mutated IGHV and standard risk FISH [4]. Recently, several studies reported the use of less toxic regimens as frontline therapy for B-CLL, such as bendamustine or chlorambucil combined with rituximab [5, 6]. We previously reported results on safety and efficacy of oral or intravenously FC as frontline therapy in CLL patients [7, 8]. Characteristics of our cohort of patients are reported in Table 1. At a median follow up of 6 years, we now report long-term outcomes and complications. After informed consent, 58 of 65 retrospectively enrolled patients with median age of 65 years were evaluable for response to treatment, with an overall response (OR) rate of 84 % [8]. Median progression-free survival (PFS) was 37 months (range 2–199), which is comparable to results from CLL4 and CLL8 trials [1, 9]. Median time to retreatment (TTR) was 42 months (range 2–199). At a median follow-up of 6 years after the beginning of FC (range