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5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This "real life" analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL ("Rete Ematologica Lombarda"), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To analyze the unpredicted event of hematological improvement (HI) during iron-chelation therapy (ICT), we reviewed a series of 53 myelodysplastic patients with transfusion dependency in a retrospective study involving 8 centers afferent to the "Rete Ematologica Lombarda". According to the IWG response criteria published in the year 2000, we observed erythroid responses in 19 patients (35.1%), 5 major (9.2%) and 14 minor (25.9%). In the assessable patients, platelet response was 8/13 (61%) and neutrophil response was 13/17 (76.4%). Only in patients with erythroid improvement, multilineage responses were observed. Apparently, patients with greater erythropoiesis dysfunction may take more advantage., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Plerixafor has been previously reported to improve PBSC collection in pts undergoing PBSC mobilization. Aim of the study was to assess the efficacy of plerixafor and G-CSF in pts with lymphoma who failed previous attempts of PBSC mobilization with conventional schemes of chemotherapy+G-CSF. 35 heavily pre-treated lymphoma pts (29 NHL, 6 HL) classified as "poor mobilizers" were enrolled in a program of compassionate use of plerixafor in 7 Italian centres of REL (Rete Ematologica Lombarda). Median number of previous lines of therapy was 3 and median number of previous attempts of mobilizations was 2. The median number of circulating CD34+ cells/μL following plerixafor was 11/μL. It was ≥10/μL in 17 pts and ≥20/μL in 10 pts; 13 were able to collect ≥2×10(6) CD34+ cells/kg with a median of 1 apheresis procedure; 4 pts collected ≥4×10(6) CD34+ cells/kg. A total of 6 pts had proceeded to transplant at the time of analysis. The median dose of PBSCs infused was 4×10(6)/kg and hematopoietic recovery was regular. In conclusion, plerixafor combined with G-CSF allows a collection of adequate number of PBSC in approximately 40% of cases of poor mobilizer, heavily pre-treated pts with lymphoma, who need consolidation with ASCT., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Flow cytometry and cytomorphology results on 92 body cavity fluids [61 effusions and 31 bronchoalveolar lavage fluids (BALF)] from hematologic malignancy were compared with retrospective clinical outcome. We observed double true positive/negative results in 67 cases (73%), and double false negative results in 2 cases (2%). Immunophenotyping accounted for true positive/negative results in 22 out of 23 mismatched cases (25%), and retained significantly higher accuracy than that of cytomorphology especially in effusions and differentiated lymphoma. In BALF analysis, immunophenotyping and cytomorphology sensitivity was 75% and 0%, respectively. Flow cytometry retains the highest accuracy in detecting neoplastic cells in body cavity fluids., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A total of 303 MM patients were retrospectively reviewed to evaluate long-term efficacy and toxicity of thalidomide alone or in combination with steroids. Overall response rate was 57% (CR/VGPR 12%). Median TTP, PFS and OS were 13.4 months, 20.6 months, and 26.2 months, respectively. PFS and OS were significantly different according to response (p < 0.0001), with better outcome in patients achieving CR/VGPR (PFS and OS 35.4 months and 63 months, respectively). PFS and OS of patients achieving SD or PR were overlapping (p = 0.3). The addition of steroids significantly increased the response rate (p = 0.01). The most clinically relevant complications were neuropathy (40%), constipation (26%), thromboembolic events (7%). Thalidomide was reduced for toxicity in 68 patients (24%) and permanently discontinued in 36 (12%). In conclusion, thalidomide produces high response rate in relapsed/refractory MM. The best outcome is observed in patients with good quality response, but even patients with suboptimal response may obtain durable survival.

Human tryptase is a serine protease expressed in mast-cells. We previously observed that AML blast cells, cultured in vitro from a KIT D816Y patient, give rise to adherent cells with mast-cell like phenotype and tryptase was released in the serum-free medium. To correlate total serum tryptase (ts-try) levels with cytogenetic features and KIT mutational status, we analyzed serum samples from AML patients at diagnosis. In 70 out of 155 patients (45%) we detected elevated ts-try (>15 ng/mL), significantly linked to t(8;21) (P < .001) and inv(16) (P = .007). In patients that achieved complete remission the ts-try decreased to normal values. In 75 patients screened for KIT mutation, we found a clear relationship between elevated ts-try and mutated patients with t(8;21) (P < .001). In conclusion, we propose that checking for ts-try at diagnosis of AML may be a simple tool to select patients to be addressed to KIT mutation screening.

Preclinical data suggest that all-trans retinoic acid (ATRA) synergizing with granulocyte colony stimulating factor (G-CSF), can improve the effectiveness of chemotherapy in acute myeloid leukemia (AML). Fludarabine 15 mg/m(2) is the minimum dose able to optimize intensification with fludarabine-arabinosylcytosine regimen. In this study 52 patients with relapsed/refractory AML obtained a complete remission (CR) rate of 69.2% after FLAIRG regimen (Fludarabine and arabinosylcytosine twice daily, idarubicin, G-CSF, ATRA). This schedule resulted effective and tolerable enabling 53% of the responding patients to receive transplant procedure. FLAIRG regimen could be proposed as a "bridge" to transplant treatment in this poor risk setting.

We studied circulating (C)CD34(+) cells by flow cytometry in 96 patients with myelodysplastic syndromes (MDS) at diagnosis, and in a subset of 35 cases during follow-up. CCD34(+) counts were stratified within both International Prognostic Scoring System (IPSS) and World Health Organization (WHO) categories. Counts >10/microl were associated with poorer leukemia-free survival, a prognostic value for evolution independent from that of WHO, and a higher progression probability within intermediate-risk IPSS and WHO classes. When serial measurements were performed, counts >10/microl more frequently correlated to evolution. Separating newly diagnosed patients on the basis of 10/microl cut-off of circulating CD34(+) cells retains prognostic utility, especially in intermediate-risk MDS.

Hyperleukocytic acute myeloid leukaemia is considered to have a poor prognosis due to high early death rate secondary to leukostasis. Supportive treatments do not seem to have reduced early exitus in this subset of patients. Prognostic impact of hyperleukocytosis on outcome has been the object of few studies. Clinical characteristics and outcome of 45 consecutive adult patients with newly diagnosed acute myeloid leukaemia presenting to our institution with a white cell count (WBC) above 100 x 10(9)L(-1) were reviewed. The outcome of this subset of patients was compared with 200 patients with a leukocyte count lower than 100 x 10(9)L(-1) similarly treated in the same period. Eight hyperleukocytic patients (17%) died of intracranial haemorrhage or pulmonary failure due to leukostasis within the first 7 days of treatment. A significant association was found between complete response (CR) and absence of hyperleukocytosis, but if early deaths were removed from analysis the difference was no longer significant. Hyperleukocytosis also significantly reduces the overall survival (OS) but does not significantly influence the disease-free survival (DFS). We reviewed in literature studies in which the outcome of series of at least 10 patients with hyperleukocytosis were compared with that of patients with a leukocyte count lower than 100 x 10(9)L(-1). Our data were consistent with those of the literature regarding the rate of early mortality and causes of death. In most of the reviewed series hyperleukocytosis does not seem to influence the outcome of patients. Avoiding early death seems to be an important step in this subset of patients. New data about pathophysiology of leukostasis are needed.

Aim of this study is to investigate the capability of Imatinib to induce an anti-leukemic effect in Core Binding Factor (CBF)-leukemia patients presenting either with extracellular juxtamembrane or kinase KIT mutations. On the basis of a screening analysis for KIT mutations, two patients with a kinase mutation and one with extracellular juxtamembrane mutation, in first or subsequent leukemic relapse, received 400mg Imatinib twice daily for 30 days. After Imatinib discontinuation, bone marrow cells were re-tested to assess the KIT mutational status and the chromosomal set. In our experience, none of the treated patients had a response by standard criteria; in particular, we did not observe any activity against acute myeloid leukemia (AML) associated with KIT kinase mutations. However, in the patient with extracellular juxtamembrane mutation, Imatinib seems to have some clinical beneficial effect and, most important, is able to abrogate the leukemic subclone carrying the mutation. Whether Imatinib, in combination with other agents, may play a role in the treatment of AML with more sensitive extracellular juxtamembrane KIT mutation remains to be determined.