Estella Matutes

..We suggest that the relatively high incidence of transformation in this series may be due to immunosuppression mainly related to fludarabine, although other agents and prior therapies may have also contributed...

..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...

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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...

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..Consolidation with high dose therapy and autologous or allogeneic stem-cell transplantation should be considered in young patients...

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

..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...

..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...

..Splenectomy is a useful treatment option in this group of patients...

..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...

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

..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...

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

..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...

..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...

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

..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...

..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...

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

..Further comparisons between flow cytometry, IHC, and FISH may be needed to ascertain the diagnostic value of the flow cytometric assay...

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

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

..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...

..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...

..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...

..Although p53 abnormalities are infrequent in SLVL, they underlie a more aggressive disease course and poor prognosis. (Blood. 2001;97:3552-3558)..

..The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia...

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

..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...

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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...

..We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial...

..Alternatively, the frequent loss of the p53 gene could be associated with the deletion of an adjacent gene, which could be involved in the pathogenesis of these diseases...

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

..The role of FCM as first line therapy deserves study as well as its combination with the monoclonal antibody Rituximab...

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

..Thus, 13q14.3 deletions could contribute to the development of overt leukaemia in T-PLL, but the involvement of more than one gene in the region cannot be excluded...

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

..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...

..To augment the limited literature on bone marrow (BM) appearances in T-cell large granular lymphocyte (LGL) leukaemia and to identify a histological signature to aid in diagnosis of this condition...

..We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine...

..The reasons for the immunophenotypic changes are unknown but it is likely that loss of CD52 antigen expression contributed to the resistance to CAMPATH-1H in one of the patients when re-treated...

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

..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...

..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...

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..While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant...

..B29 (CD79b) is present in the membrane at a later stage compared to its cytoplasmic expression and found in mature B blasts (B-ALL) that express membrane Ig as it is in normal and leukaemic B lymphocytes...

..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...

..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...

..8-fold (OR = 2.8, 95% confidence interval: 1.1-6.9). Our findings suggest that heritable GST status may influence the risk of developing CLL...

..We conclude that DCF is a useful therapy for the treatment of T-cell leukaemias, in particular Sezary syndrome and T-PLL, and should play a part in strategies to improve the natural history of this group of lymphoid malignancies...

..FC might be slightly more sensitive than BMB to detect MRD in CLL, whereas BMB may be slightly better than FC in NHL...

..03). While transformation in the bone marrow is frequently refractory to therapy and associated with poor outcome in SMZL, lymph node transformation responds well to chemotherapy with durable progression-free and overall survival...

..We concluded that the detection of cyclin D1 expression by flow cytometry in cell suspensions could be applied routinely to the study of B-lymphoproliferative disorders and may be of value for their diagnosis and management...

..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 response has, so far, been sustained for 2 1/2 years after stopping treatment...

..The disease is sensitive to AML induction regimens and long-term survival can be achieved with BMT in first complete remission...

..We also describe objective response to antiviral therapy. To our knowledge, this is the first report of such presentation and response...

..The mechanism of inactivation appeared to be unusual because multiple structural lesions on one allele were often observed...

..The cellular distribution of lymphopain expression, together with the functional demonstration of lymphopain-associated proteinase activity in vitro, is suggestive of a role for lymphopain in immune cell-mediated, cell killing...

..Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue...

..In conclusion, our study demonstrates that MSI does not have a prominent role in the pathogenesis of B-CLL...

..This suggests these regions may harbour a susceptibility locus for CLL. There is also some evidence that chromosome regions 2p12-p14 and 4q11-q21 may harbour predisposition genes...

..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...

..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...

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

..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...

..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...

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

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

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..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...

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

..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...

..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)...

..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...

..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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..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...

..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...

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

..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...

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

..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...

..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...

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