Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL).

BACKGROUND: Splenic marginal zone lymphoma (SMZL) with or without villous lymphocytes is an indolent lymphoma that typically affects elderly patients. Treatment is required in symptomatic cases. Splenectomy remains one of the first-line options in patients fit for surgery. The best therapeutic strategy has not yet been identified. Among different possible chemotherapeutic approaches, purine analogues, alone or in association with rituximab, seem to be a valid therapeutic choice. PATIENTS AND METHODS: Fifty SMZL patients were treated with cladribine with or without anti-CD20 mAb. RESULTS: Forty-six of 50 patients were assessable for response. Overall response rate was 87%: 24 of 46 patients (52%) achieved a complete hematological response (CR), 16 of 46 (35%) a partial response and 6 (13%) were unresponsive. Interestingly, 15 of 24 cases (62%) in CR also achieved a molecular remission. CONCLUSIONS: The present results indicate that this schedule is a valid therapeutic approach in SMZL. Addition of rituximab significantly improved quality of response and consequently the outcome of the disease.

Vascular endothelial growth factor polymorphisms in mantle cell lymphoma.

In this study, we determined the allele and genotype frequencies of vascular endothelial growth factor (VEGF) G+405C, C-460T, C+936T and C-2578A single nucleotide polymorphisms (SNPs) in 32 patients affected by mantle cell lymphoma (MCL) and 58 healthy controls. Real-time PCR combined with melting curve analysis was used for the determination of SNP alleles. A significant difference in the allele frequency of VEGFC-460T and C+936T SNPs in MCL and healthy cases was not observed. On the contrary, VEGF G+405C and C-2578A SNP allele distribution was significantly lower in the patient group than among normal controls (p = 0.014, p = 0.001). This observation suggests that further investigation is warranted, both in vitro and in a larger series of patients, to further examine the role of VEGF polymorphisms in the pathogenesis of MCL. In addition, the use of quantitative real-time PCR combined with a melting curve analysis method in the detection of the 4 VEGF SNPs may have the potential to replace older and more time-consuming PCR-RFLP methods and bears further investigation.

PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells.

PS-341 (Bortezomib) is a dipeptide boronic acid proteasome inhibitor with antitumor activity that induces apoptosis in different human cancer cell lines. We investigated effects of PS-341 (Bortezomib) on cell proliferation, cell cycle progression, induction of apoptosis and differentiation in a megakaryoblastic (MO7-e) cell line. PS-341 was able to retain NF-kappaB in the cytoplasm and inhibit cell growth (IC(50)=22.5 nM), in a dose/time-dependent way. This anti-proliferative activity resulted to be lineage-specific, because other leukemic cell lines (KG1a, K562/R7, HL60/DNR) were unaffected by the PS-341 treatment. Moreover, PS-341 in MO7-e induced a significant pro-apoptotic effect from 10 nM concentration (40% versus 12% in the control, p<0.05). On the other hand, at lower concentration (5 nM), Bortezomib blocked cell cycle in the G2 phase. Finally, this compound was able to down-regulate WT1 expression. No significant effects on cell differentiation were found. Because a spontaneous NF-kappaB activation has been reported in megakaryocytes from patients affected by myeloproliferative disorders, Bortezomib would so be an attractive therapeutic tool for these malignancies, including essential thrombocythemia or idiopathic myelofibrosis. Preliminary data show an inhibiting activity of Bortezomib in the megakaryocytic colonies formation. Finally, also down-regulation of the WT1 gene Bortezomib-driven could be relevant, because of the role that this gene would play in the pathogenesis of acute and chronic myeloproliferative disorders.

Contemporaneous appearance, 18 years after allogeneic bone marrow transplantation, of myelodysplastic syndrome in the patient and the donor.

We report the case of the development of two different stages of the same clonal disorder in two patients sharing the same bone marrow due to a previous bone marrow allotransplant. The transplanted patient developed severe aplasia with myeloid blasts, different from those of the previously cured leukemia. Chimerism evaluated by microsatellite analyses confirmed a full donor phenotype. At the same time, the donor of the bone marrow transplantation developed a refractory anemia with excess blasts. We speculate on the presence of an undetectable pre-existing pathological clone in the transplanted bone marrow, which have evolved in the two patients.

Combination of morphology, flow cytometry and PCR assay to detect bone marrow infiltration in B-cell non-Hodgkin's lymphomas.

AIMS: Morphology on bone marrow biopsy (BMB) samples has historically been the primary method used to detect bone marrow (BM) infiltration in B-cell non-Hodgkin's lymphoma (NHL), while fl ow cytometry (FC) and PCR assays have been generally used as ancillary methods. In this study we evaluated a combined approach utilizing all three methods to detect BM infiltration in patients with NHL both at diagnosis and after therapy. MATERIALS AND METHODS: We analyzed 193 patients with NHL, who received simultaneous BMB, FC and PCR assays. Morphology on histologic specimens was used to assess infiltration pattern and immunohistochemistry, FC to analyze immunophenotype, PCR to identify IgH rearrangement, BCL-1/JH and BCL-2/JH translocation. RESULTS: Morphology, FC and PCR assays agreed in 142 cases (73.5%) with more concordance at initial diagnosis than during postchemotherapy follow-up. PCR was the single best-performing test, while combination of morphology and PCR yielded a higher sensitivity than individual methods and was similar to PCR + FC. We observed little added benefit using a third approach. CONCLUSION: Given the initial importance of histological information evident by morphology, our data suggest that combination of morphology and PCR should be considered the gold standard for evaluation of BM infiltration at diagnosis, while combination of PCR + FC should be employed during post-treatment follow-up.