Estella Matutes

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..Fluorescence in-situ hybridization (FISH) analysis also provides prognostic information, chiefly by detecting 17 (p53 locus) and 11q deletion, and may determine the type of therapy...

..In this work we analyze diagnostic criteria for BAL...

..Transformation to large cell is seen in 6% of patients. The inferior survival in HCL-variant compared with typical HCL cases may reflect the chemotherapy resistance...

..Those monoclonal antibodies that are relevant to the characterisation of the chronic lymphoproliferative disorders and that could be incorporated in a routine practice are discussed...

..This is the first case documented by molecular methods of the transformation of the pre-existing clone...

..Both provide relevant information in terms of diagnosis, course of the disease, prognosis and pathogenesis...

..These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features...

..These cases serve to highlight the biological and cytogenetic heterogenity of DLBL and emphasize the need for complementary investigations in the characterization of this entity...

..To the authors' knowledge, there is no standard treatment for patients with T-cell large granular lymphocyte (LGL) leukemia. Available data are limited by patient numbers and coexisting pathologies...

..We conclude that 7% may be a more useful threshold for disease progression than higher values of CD38...

..However CD123 does not allow the distinction between HCL-variant and SLVL, as both are CD123 negative...

..These four SNPs map to a 3 kb region of the 3'-UTR of IRF4, consistent with the causal basis of the association being mediated through differential IRF4 expression...

..001 for SLVL deaths). We conclude that SLVL is mainly a disease of the elderly with a relatively benign course but, when treatment is required, splenectomy is beneficial...

..We highlight the resistant nature of the LGL clone and discuss the relative merits of immunomodulatory type therapy in this disease...

..Immunophenotyping is an essential tool for the diagnosis of these two disorders, for monitoring and assessing response to therapy, and for distinguishing them from other B-cell malignancies...

..2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy...

..DNA sequencing adds little to these methods in identifying the population at risk...

..Age, Ph(+), and AML therapy were predictors for poor outcome (P < .001; P = .002; P = .003). MPAL is confirmed to be a poor-risk disease. Adults and Ph(+) patients should be considered for transplantation in first remission...

..In conclusion CHOP-Z is safe and in those who achieve a complete response it was associated with prolonged overall survival...

..02). In particular, amplification of 2p and deletion of 6q were both more frequent. Cases with >20%TP53-deleted cells had the worst prognosis in the LRF CLL4 trial...

..We conclude that treatment with alemtuzumab may offer new hope to patients who otherwise have a bleak prognosis...

..The patient has twice achieved a good response to pentostatin after failure of combination chemotherapy. This is the first report of the successful use of the purine analogue pentostatin in the management of GSSD...

..FMC7 is of greater diagnostic value than CD20 for distinguishing CLL from other B-cell disorders; we recommend its continued use for this purpose...

..This study provides a practical strategy to distinguish haematogones from B-ALL cells in BMTB...

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..Our results indicate that quantitative analysis of CD34 and CD117 may be useful to detect minimal residual disease (MRD) and could be tested in a future to monitor therapy in AML...

..A provisional diagnosis of acute myeloid leukemia, FAB type M2, was made in a 24-year-old woman. Immunophenotyping led to reassessment of the diagnosis...

..Differences seen between MCL and CLL in spleen size, and in response of the leucocytosis suggest a central role for the spleen in the evolution of MCL with leukaemia...

..This study demonstrates that HDMP alone or in combination with other agents is a useful treatment strategy in refractory CLL including patients with p53 abnormalities...

..32 (rs11083846, PRKD2; P = 3.96 x 10(-9)). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL...

..The incidence of the latter two events was, however, higher than previously reported. Deletion of the TP53 gene predicted resistance to chemotherapy, highlighting its importance in this disease process...

..In atypical CLL, histology and/or molecular genetics may be required to exclude other B-cell disorders...

..In particular, the use of Campath-1H, in T-PLL has more than doubled median survival. The role of allogeneic transplant with nonmyeloablative conditioning needs to be explored further...

..The presence of a high incidence of abnormalities in the established hotspot areas and in particular the finding of biallelic deletions is indicative of the existence of genes important for the pathogenesis of SLVL in these areas...

..Common ATM missense mutations were not overrepresented. The data support previous observations that ATM mutation is associated with B-CLL. However, ATM mutations do not account for familial clustering of the disease...

..Here, we review the current status of knowledge about inherited susceptibility to CLL...

..The structures of the ATM duplications suggest they may arise from an error in somatic hypermutation. We suggest that aberrant components of somatic hypermutation may contribute to the defective DSB repair characteristic of cancer...

..This is to our knowledge the first description of amplification of the CCND1/IGH fusion gene in a human neoplasm, which may have played a role in the fulminating course of the disease in this patient...

..However, these neoplasms also differ from CLL cytologically and in their immunophenotype...

..In conclusion, DAT status at the time of initiation of therapy provides a new prognostic indicator, although FC may protect against AHA. This trial was registered at http://isrctn.org as no. 58585610...

..They continue to be effective at second- and even third-line therapy; however, alternative treatments are needed for patients who are or have become refractory to these agents or whose remissions are shorter with each course of therapy...

..True cure in HCL remains elusive, but the addition of monoclonal antibodies may be beneficial. Our results suggest that achieving CR should remain the main goal of treatment...

..Chronic lymphoproliferative disorders include a variety of diseases which are often a diagnostic problem for clinical hematologists...

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..We find no evidence against a diagnosis of MCL in the nonnodal group and suggest that mutated IgVH genes may help identify patients with indolent disease...

..Our results indicate that marginal zone lymphomas at different anatomical localizations may derive from a similar B-cell subset...

..Our data suggest that SMZL constitute a genetically heterogeneous disease where gain of 3q25 and loss of 7q31 are the most likely imbalances to be involved in the pathogenesis of the disease...

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..The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells...

..00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL...

..This study aimed to assess the frequency, relationship and impact of p53 abnormalities and those of its inhibitor mdm2 in blastoid and non-blastoid MCL in leukemic phase...

..However, a role for RFP2 in the pathogenesis of MM cannot yet be excluded, given that alternative mechanisms such as haploinsufficiency remain possible...

..80-1.31). A meta-analysis of this study and five other smaller published studies provides no evidence of relationship between this P2X7 polymorphism and risk of CLL (odds ratio = 0.99, 95% confidence interval: 0.74-1.32)...

..214). We confirm the efficacy of alemtuzumab in refractory CLL irrespective of p53 deletions, and advocate its introduction earlier in disease course...

..Despite its efficacy the combination is not easily manageable because of the high rate of opportunistic infections...

..Detectable molecular disease by PCR was highly predictive of disease recurrence. It is of concern that 5 of 65 (8%) patients developed posttransplant acute myeloid leukemia/myelodysplastic syndrome...

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..97 (95% CI, 0.79-1.18) and 0.88 (95% CI, 0.62-1.24), respectively. This data indicate that the MTHFR polymorphisms C677T and A1298C do not significantly contribute to an inherited genetic susceptibility to CLL...

..During follow-up post-treatment, seven delayed responses (54%) were observed, improving the initial overall response rate of 61% to a final response rate of 77%...

..Pregnancy thus appears to have a beneficial effect on neutrophil count in T-cell LGL leukaemia...

..01). None of the regions coincided with areas of common chromosomal abnormalities frequently observed for CLL. These findings strengthen the argument for an inherited predisposition to CLL and related B-cell LPDs...

..4% (95% confidence interval, 2.5-24%). No analysed potential risk factor was predictive for MDS/AML development. We hypothesise that potential causative factors are fludarabine, low cell dose and transplant conditioning...

..These observations provide evidence that familial CLL is essentially indistinguishable from sporadic CLL, favoring a genetic basis to disease development in general rather than a simple environmental etiology...