Ayalew Tefferi

..The objective is to help the nonhematologist recognize when a subspecialty consultation is reasonable and when it may be circumvented, thus allowing a cost-effective and intellectually rewarding practice...

..Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study...

..In contrast, only 40% partial response rate was seen in 10 HES cases. FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis...

..We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities...

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..02), but not JAK2V617F allele burden, thrombosis, hemorrhage, leukemic/fibrotic transformation, or survival. We conclude that cytogenetic anomalies occur infrequently at PV diagnosis and do not confer an adverse outcome...

..The current study was designed to provide additional data in this regard...

..Our results revealed this new FISH assay accurately detects these abnormalities and will be a useful clinical test for patients with myeloid neoplasms and eosinophilia...

..Additional important prognostic factors not taken into account by the IPSS include the baseline erythrocyte indices, lymphocyte count, and clonal burden...

..However, compared with the PRV-1 assay, mutation screening for JAK2(V617F) displayed greater accuracy in distinguishing PV from SP...

..A possible association with thrombotic complication has also been considered...

..We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders...

..The main objective of this study was to refine DIPSS by incorporating prognostic information from karyotype, platelet count, and transfusion status...

..Therefore, although the presence of JAK2(V617F) in ET appears to promote a PV phenotype, it might not carry treatment-relevant information...

..We conclude that neither the SCLL phenotype nor blood eosinophilia is a consistent feature of FGFR1-associated 8p11.2 translocations; conversely, FISH might not always reveal FGFR1 involvement in typical SCLL...

..These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell...

..02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV...

..Treatment with busulfan or interferon-? is usually effective in hydroxyurea failures. Screening for clinically significant AvWS is recommended before administrating aspirin in the presence of extreme thrombocytosis...

..The presence of 0, 1, 2, and > or =3 adverse factors defines low, intermediate-1, intermediate-2, and high risk disease, respectively. We examined the additional prognostic relevance of karyotype...

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..When used, lenalidomide therapy induced hematological and cytogenetic remissions in del(5q)-positive PMF. The current study identifies PMF as another del(5q)-associated myeloid malignancy with characteristic megakaryocyte morphology...

..Taken together, these observations suggest that JAK2(V617F) is an acquired myeloid lineage-specific mutation that engenders a pathogenetic relevance for the PV phenotype in MPD...

..The current study highlighted the prognostic relevance of leucocytosis on various aspects of the disease in PV...

..For the current study, the authors explored the relation between specific cytogenetic clones and JAK2(V617F) mutational status in patients with MMM and the effects on treatment response to erythropoietin (Epo)...

..002), not in those with low-risk disease (P=.42). These observations are encouraging and suggest a salutary effect from modern therapeutic approaches in PMF...

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..This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance...

..In the current review, we provide a simplified algorithm for distinguishing the various causes of clonal and idiopathic eosinophilia and discuss current therapy, including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab)...

..Our study also suggests that the natural history of a JAK2V617F-positive "occult" MPN might be different from that of a typical MPN...

..In other words, when RARS and RCMD-RS were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations...

..To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results...

..We conclude that del(5q), although most prevalent in MDS, is seen across the spectrum of myeloid disorders including MPD and its occurrence in lymphoid disorders might signify, for the most part, an occult myeloid clone...

..0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL...

..The new system displayed a stronger discriminative value, between risk categories, compared with currently existing prognostic models...

..86% test accuracy). The current study suggests that PRP serotonin concentration might be considered as one of the several biological markers that complement each other for the diagnosis of PV...

..The current communication features a comprehensive clinical summary of both secondary and primary eosinophilic disorders with emphasis on recent developments in molecular pathogenesis and treatment...

..Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease...

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..Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon...

..Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD...

..2, 95% confidence interval 1.6-3.1; P < .01). The present information complements DIPSS-plus in the selection of primary myelofibrosis patients for high-risk treatment approaches...

..The current prospective study does not support an independent prognostic value for PB CD34 count in MMM...

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..The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown...

..We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes...

..30%; P = 0.003). Multivariable analysis revealed that these associations were independent of other risk factors for thrombosis. High JAK2V617F allele burden clustered with pruritus (P = 0.002) but did not affect thrombosis rates...

..While many questions remain about the optimal use of newer agents, the long-standing perception of MDS as a syndrome where therapeutic nihilism is the only realistic approach is slowly beginning to change...

..Two other PSSs, Cervantes and Mayo, were recently reported as being more useful in younger patients. The current study compares these 3 PSSs among all age groups...

..The current study validates the prognostic relevance of the WHO subclassification of SM and provides additional information of value in terms of both risk stratification and interpretation of clinical presentation and laboratory results...

..All surviving patients displayed excellent performance status without ongoing chronic graft versus host disease. We conclude that ASCT is an effective salvage therapy for fludarabine-refractory CLL but late relapses can occur...

..Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT...

..Clinical responses did not correlate with improvements in either intramedullary fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears to be a promising drug regimen for treating cytopenias in patients with MMM...

..Therapy-related APL is sensitive to standard therapy with no cases of resistance or relapse seen. The inferior OS of the t-APL was due to induction mortality, possibly reflecting prior therapy...

..In patients with clonal eosinophilic disorders and mast cell disease, the use of molecular diagnostics to identify novel mutations and gene rearrangements, has resulted in superior diagnostic and therapeutic strategies...

..The current prospective study addresses this issue in the context of currently accepted independent prognostic variables...

..The purpose of this review is to summarize current concepts and recent advances in the pathogenesis and treatment of adult mast cell disease...

..However, to the authors' knowledge, information regarding risk factors for leukemic transformation in primary myelofibrosis is limited...

..37; 95% confidence interval, 0.24-0.58) cytogenetic risk categorization (P < .01). The ability to prognostically dissect a specific IPSS category has major therapeutic implications...

..However, quantifying neutrophil PRV-1 mRNA, while complementary to other tests, is not in itself sufficient for the diagnosis of PV...

..We discuss histologic, cytogenetic and molecular changes in MPN and illustrate their integration into practical diagnostic algorithms...

..All other patients were NPM1-wild type in the region analysed. In conclusion, C-terminal NPM mutations are uncommon in chronic myeloid neoplasia, but if present may represent an evolving leukaemic clone...

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..8 (1.7-130.8). The prognostic relevance of MK was not accounted for by the Dynamic International Prognostic Scoring System. We conclude that MK in primary myelofibrosis is associated with extremely poor overall and leukemia-free survival...

..These results are contrary to previous reports that suggested inferior survival as well as poor response to alpha interferon therapy in CML patients carrying der(9) deletions...

..Multivariable analysis identified Ph mosaicism as a risk factor for shortened survival. Due to the small sample size, the current preliminary observations require validation in a larger group of patients...

..In addition, it is unclear whether patients with MDS-associated acquired alpha thalassaemia (ATMDS), a special subgroup with a very high incidence of point mutations in the ATRX gene, have an especially high incidence of RUNX1 mutations...

..The study also suggests either a megakaryocyte origin or a megakaryocyte effect for the putative angiogenic cytokine...

..Consistent with previous observations in animal models, our observations suggest the possibility that altered TPO regulation resulting in sustained ligand excess may have pathogenetic relevance in MMM...

..The current study provides direct evidence for the clonal involvement of both B and T lymphocytes in MMM. A larger study is needed to clarify the relevance of the observed interpatient heterogeneity in clonal constitution...

..Myocardial biopsy revealed eosinophilic infiltration and degranulation, and the cardiogenic shock was reversed with the prompt institution of corticosteroid therapy...

..These observations make it necessary to re-examine current disease classification and treatment algorithms in eosinophilic disorders...

..In the future, global analysis of gene expression patterns may help overcome diagnostic dilemmas, refine disease classification, and lead to an improved understanding of the pathogenesis of ET...

..Imatinib is considered investigational for the treatment of hematologic malignancies without a defined molecular drug target, such as polycythemia vera, myelofibrosis with myeloid metaplasia, and acute myeloid leukemia...

..In contrast, BM angiogenesis, reticulin fibrosis, and levels of MC mediators showed no prognostic relevance...

..These issues are discussed within the context of clinical practice...

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..In SMCD, the presence of D816V mutation was significantly associated with advanced age, an aggressive clinical course, increased bone marrow mast cell content, and chronic myelomonocytic leukemia...

..We conclude that bone marrow angiogenesis characterizes a percentage of patients with SMCD and that the pathogenesis may not necessarily be linked to the mast cells themselves...

..Advanced age and a prior history of thrombosis are the major predictors of thrombotic complications...

..CONCLUSION: This study confirmed relevant and frequently durable palliation of symptoms in about half the patients. 2-CdA is a reasonable palliative option in postsplenectomy patients with MMM who have problematic myeloproliferation...

..The overall PR or CR to splenectomy combined with medical therapy was 84%. CONCLUSION: Splenectomy should be considered safe and efficacious for thrombocytopenia associated with SLE...

..Collectively, these results identify adaphostin as a mechanistically distinct CML-selective agent that retains activity in STI571-resistant cell lines...

..04) and a higher frequency of palpable splenomegaly (P < 0.01). CONCLUSION: Overall disease progression and response to immunosuppressive therapy are similar between T-cell and natural killer-cell variants of LGLL...

..In general, conventional therapy for SM is suboptimal, and efforts are under way to develop and employ small molecule drugs that target mutant KIT...

..The clinical implications of this finding are discussed...

..Optimal therapy for an individual patient requires a sound understanding of disease risk factors, as well as a full appreciation of the risk to benefit ratio for a specific treatment modality...

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..0001 for each). Furthermore, we demonstrate that peripheral blood D-FISH can be used as a surrogate for cytogenetic studies in monitoring cytogenetic remission status...

..The presence of +8 did not appear to adversely affect the outcome of patients with favorable karyotypes...

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..Cytopenias occurred in all five 'mismatch' patients but not in two patients with 'match', suggesting that KIR/HLA-I mismatch may contribute to the suppression of haematopoiesis...

..He was hospitalized for neutropenic fever and was diagnosed to have pulmonary aspergillosis. He died of multisystem failure 8 1/2 months after being diagnosed with AMM...

..The results confirm the diagnostic value of Kit immunohistochemistry in MCD and suggest a biologically relevant heterogeneity in TGFbeta1R expression among patients with SMCD-HD...

..The role of aspirin is being readdressed by an ongoing controlled study. Transformation of PV into either myelofibrosis with myeloid metaplasia or acute leukemia remains a major complication that may not be influenced by current therapy...

..In the current review, we summarize the general concepts regarding angiogenesis, assessment of angiogenesis in hematological malignancies and then the current literature on angiogenesis and anti-angiogenic therapy in MMM...

..All patients who responded stopped other treatments and reduced imatinib mesilate to 200 mg per week. This drug effectively controls eosinophilia in patients with hypereosinophilic syndrome and normal interleukin-5 concentrations...

..This study shows that survival rate of hematopoietic stem cell transplant recipients with diffuse alveolar hemorrhage is better than previously reported, and that early onset and autologous transplant are favorable prognostic indicators...