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Purpose of Review: A working group of six expert physicians convened to assess the spectrum of multiple myeloma relapse presentations, discussed the features that can define the disease as aggressive and not aggressive, and established whether this information could help in selecting treatment together with the characteristics of disease and of patients and type of prior therapy. Recent Findings: The working group agreed that relapse should be distinguished between biochemical and clinical according to IMWG. Moreover, the expert panel defined "aggressive disease" as a clinical condition that requires therapy able to induce a rapid and as deep as possible response to release symptoms and to avoid impending danger of new events. According to this definition, relapse was considered aggressive if it presents with at least one of the following features: doubling of M protein rate over 2 months, renal insufficiency, hypercalcemia, extramedullary disease, elevated LDH, high plasma cell proliferative index, presence of plasma cells in peripheral blood, or skeletal-related complications. Moreover, the panel agreed that this classification can be useful to choose therapy in first relapse together with other patient, disease, and prior therapy characteristics. So, this item was included in a new therapeutic algorithm. Summary: The treatment choice in MM at relapse is wider than in the past with the availability of many new therapeutic regimens leading to increased diversity of approaches and relevant risk of inappropriate treatment decisions. A practical classification of relapses into aggressive or non-aggressive, included in a decisional algorithm on MM management at first relapse, could help to make the appropriate treatment decisions. [ABSTRACT FROM AUTHOR]

Recent reports identify the ratio between absolute neutrophil count (ANC) and absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. We retrospectively examined the NLR in a cohort of 309 newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents. NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9 (range 0.4-15.9). Higher NLR was independent of international staging system (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS estimates were, respectively, 18.2 and 36.4 % for patients with NLR ≥ 2 versus 25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years, N = 179), NLR ≥ 2 had a negative prognostic impact on both PFS and OS, in all ISS stages. By combining ISS stage and NLR in a model limited to young patients, we found that 19 % of the patients were classified as very low risk, 70 % standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and 10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and very high-risk groups. We found NLR to be a predictor of PFS and OS in MM patients treated upfront with novel agents. NLR can be combined with ISS staging system to identify patients with dismal outcome. However, larger cohorts and prospective studies are needed to use NLR as additional parameter to personalise MM therapy in the era of novel agents. [ABSTRACT FROM AUTHOR]

The diversity of life is made up not only of the diversity of plants and animal species, habitats and ecosystems, but also of the diversity of human cultures. These diversities interact with one another in complex ways and express the mutual adaptation between humans and the environment at local level. Sicilian traditional agro-ecosystems, due to the history of the territory and the resulting social and economic context, are configured in a heterogeneous mosaic rich in residual features of environmental value, which enhance the connectivity of the ecological network and support a high proportion of species that are rare or of conservation concern. As a case study we analyzed the characteristics of the cultural and natural landscape of the Madonie Mountains (Sicily), acknowledged as one of the most relevant biodiversity hotspots in the Mediterranean. In a G.I.S. environment, we created a digital naturalness grid map and a floristic map including extensive data collected in field. We measured landscape naturalness degree, using the Naturalness Evaluation Index, and analysed its relationship with plant species distribution. We produce evidence that the cultural processes that shape a traditional landscape can foster an amount of specific richness disproportionate to the area covered. The presence of even limited surfaces with remnant semi-natural vegetation cover, scattered within the agricultural land mosaic, positively affects biodiversity. Therefore, we suggest that environmental management plans and policies aimed at nature and biodiversity conservation should take into account not only natural and semi-natural habitats but also the key role of agro-ecosystems. [ABSTRACT FROM AUTHOR]

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100 000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on lenalidomide plus cytarabine induce which induced remission that can be predicted by genetic profiling in older people with acute myeloid leukemia.

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain. [ABSTRACT FROM AUTHOR]

The article presents the first prospective study of initial treatment in primary plasma cell leukemia (PPCL) based on a combination of lenalidomide and low-dose dexamethasone (Ld). It notes the capability of Ld to ameliorate overall response rate (ORR) and at least very good partial response (VGPR) rate when compared with any other reported treatment conducted without novel drugs. It also reveals that PPCL patients have more compromised marrow and renal function than multiple myeloma patients.

A letter to the editor is presented about a simultaneous occurrence of acute myeloid leukemia with mutated nucleophosmin in the same family.

A letter to the editor in response to the article "A western blot assay for detecting mutant nucleophosmin (NPM1) proteins in acute myeloid leukaemia" published online on June 19, 2008 is presented.

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A letter to the editor is presented about the absence of nucleophosmin leukaemic mutants in B and T cells from AML with NPM1 mutations that is published within the issue.

The monophyly and evolution of Cynara was investigated using ITS sequence data. Parsimony analysis supports the monophyly of Cynara sensu lato, i.e. including the distinctive taxa C. humilis and C. tournefortii. This contradicts the recent decision to create a new monotypic genus Arcyna for C. tournefortii. A hypothesised close relationship between C. tournefortii and Silybum Adans. is also refuted. Four of the five species of Cynara, for which multiple accessions were sequenced, were shown to be monophyletic but C. baetica was found to be non-monophyletic. Free energy estimates for ITS1 secondary structure and conservation of the 5.8S region suggest that this is not due to the occurrence of pseudogenes. Hybridisation is a plausible explanation but evidence for the likely parents involved in such an event is inconclusive. [ABSTRACT FROM AUTHOR]

Summary:The main aim of this paper was to compare results of Genescan and real-time PCR methods in order to detect contamination in harvests from patients with follicular lymphoma. The secondary goal was to evaluate the efficacy of Rituximab as an in vivo purging agent. A total of 23 patients had been treated with CHOP followed by either high-dose therapy (12 patients) or high-dose plus Rituximab (11 patients), both followed by autologous transplantation. Results show that 86% of harvests from patients treated whith Rituximab were PCR-negative compared to 14.3% from controls. Real-time PCR was more sensitive than Genescan PCR; quantitative analysis revealed a correlation between the amount of contamination in the harvests and relapse after transplantation. Whereas all patients reinfused with negative aphereses achieved complete remission and showed a significantly better 5-year PFS (100%) compared to those reinfused with contaminated samples (41%), a very low amount of contamination does not appear to negatively affect outcome, suggesting that determination of a cutoff in the contamination level of harvests could be useful. Results suggest that real-time PCR is superior to Genescan PCR to select transplantable harvests and confirm the ability of Rituximab as an in vivo purging tool for follicular lymphoma.Bone Marrow Transplantation (2003) 32, 57-63. doi:10.1038/sj.bmt.1704102 [ABSTRACT FROM AUTHOR]

Summary:We performed a randomized study to compare 'G-CSF alone' (administered at dose of 10?mcg/kg/day) and 'cyclophosphamide plus G-CSF' (cyclophosphamide at dose of 4?g/m2 and G-CSF at dose of 10?ug/kg/day), as PBPC mobilization schedules in 52 patients with NHL or HD. Randomization was stratified according to the amount of previous chemotherapy (?2 and >2 lines of previous chemotherapy). Mean CD34+ cell peak in P.B., mean 'Total CD34+ cells' harvested and percentage of patients successfully mobilized, in the group mobilized with 'G-CSF alone' vs the group mobilized with 'cyclophosphamide plus G-CSF', were: 35.3 x 106 vs 45.8 x 106/l (P=0.3), 5.4 x 106 vs 6.8 x 106/kg (P>0.9) and 50 vs 61% (P=0.4). No differences were observed in the stratum of less pretreated patients. However, in the stratum of patients who had previously received more than two lines of chemotherapy, CD34+cell peak (P=0.05) and percentage of successful mobilization (P=0.01) were higher when 'cyclophosphamide plus G-CSF' was used. Using logistic regression, both age and mobilization with 'G-CSF alone' were significantly associated with a low CD34+ cell peak in P.B. However, in the stratum of less pretreated patients, only age was significantly associated with this risk.Bone Marrow Transplantation (2003) 31, 747-754. doi:10.1038/sj.bmt.1703912 [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a followup of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated. [ABSTRACT FROM AUTHOR]

An increase of angiogenesis has been shown in idiopatic myel-ofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count <300 x 10[sup9]/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one. Leukemia (2001) 15, 976-980. [ABSTRACT FROM AUTHOR]

Abdominal and back pain has until now been reported as a first sign of severe varicella in immunocompromised children only. We report two adult leukemia patients in whom these symptoms preceded visceral dissemination of varicella infection. Recognizing that this syndrome may occur in adult patients is of clinical importance, since it allows early diagnosis and treatment of the infection. [ABSTRACT FROM AUTHOR]