Jm Goldman

..This has led to the emergence of a number of alternative treatment strategies designed to target the leukemic cell which are resistant to imatinib...

..This choice may be based primarily on considerations of cost or possible side effects...

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..The era of tyrosine kinase inhibitors (TKI) began in 1998 and today the use of the original TKI, imatinib, has replaced SCT as initial therapy for patients who present with CML in chronic phase...

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..For the minority of patients who are judged to have failed initial treatment with imatinib at standard dosage or increased dosage, the use of second-generation TKI or allogeneic stem cell transplantation must be considered...

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..TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels...

..CONCLUSIONS: The addition of sHHT should be considered for patients on imatinib who fail to obtain low levels of minimal residual disease...

..Here, we report our experience in treating patients at a single institution in a setting where all events were recorded...

..021). This suggests that MIP-1alpha contributes to the pathogenesis of bone disease in MM and possibly in tumour growth, as reflected by its impact on survival...

..64). Our findings suggest that cytogenetic responders obtain benefit from imatinib but patients who show no cytogenetic response should be given alternative treatment without delay. We confirmed these results in a case-matched analysis...

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..This case demonstrates that imatinib mesylate can be highly effective in the management of patients who have relapses after allograft for CML...

..Kinase domain (KD) mutations in the BCR-ABL gene are associated with resistance to imatinib in chronic myeloid leukemia (CML) but their incidence and prognostic significance in chronic phase (CP) patients without resistance are unclear...

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..The advent of imatinib has thus necessitated a fundamental reappraisal of the approach to the initial management of CML...

..The goal of this study was to determine the efficacy of the 2009 H1N1 vaccine in patients with hematologic malignancies...

..In general, the LeukemiaNet criteria have useful predictive value, but a case could now be made for combining the categories "failure" and "suboptimal response."..

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..However, it has not yet been established which of the patients in whom imatinib treatment fails are likely to benefit from therapy with second-generation tyrosine kinase inhibitors...

..05%; increases that never exceeded 0.05% had no predictive value. The finding of a kinase domain mutation in a patient in CCyR, though rare, also predicted for loss of CCyR...

..There were no grade III or IV non-haematological adverse effects. Grade I fatigue, hypocalcaemia and fever were common side effects. No responses were demonstrated after 6 months on the combination...

..Overall, the results suggest that SOCS-2 is a component of a negative feedback mechanism; it is induced by Bcr-Abl but cannot reverse its overall growth-promoting effects in blastic transformation...

..Given the high rate of primary imatinib resistance in blast crisis, the potential of activating such alternative pathways appears to correlate with disease progression...

..Undoubtedly, the suggestions made here will require revision as we acquire further information on the utility of imatinib...

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..This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third-generation aminobisphosphonate, in bone turnover and disease activity in MM patients...

..01). Out of 155 patients refractory to IFN pre SCT, 70% achieved a cytogenetic response post SCT, which was complete or major in 31%. IFN refractory patients who sustained a CCR or MCR for 1-2 years after SCT had an excellent outcome...

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..01 and 0.03 respectively). We conclude that heterogeneity in the CML patient population is analogous to the constitutional diversity in normal subjects...

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..We conclude that survival after onset of BT has improved in recent years but is still unsatisfactory. We speculate that the combined use of STI571 with cytotoxic drugs may offer additional benefit...

..It is likely that the role of imatinib, used alone or in combination with other agents, will be more clearly defined in the near future...

..This article reviews evidence for the safety and efficacy of imatinib and allogeneic stem cell transplantation and suggests strategic approaches to treatment in the new era of tyrosine kinase inhibition...

..CML patients without comorbidities (HCT-CI score 0) with normal CRP levels (0-9 mg/L) may therefore be candidates for early allogeneic HCT after failing imatinib...

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..The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL-positive chronic myeloid leukemia...

..Thus, STI571 + FTI, STI571 + AG490 and IFN-alpha + ATRA may be better combination therapies for CML than STI571 + IFN-alpha, IFN-alpha + Ara-C or STI571 + AG490 + FTI...

..Further experience with the use of imatinib as a single agent or in combination with other anti-leukemic agents may alter the picture in the near future...

..015 and 0.04, respectively).Fas, FasL, and caspase activation may play an important role in regulating myeloid progenitor cell kinetics...

..This supports the use of CTL with this specificity for treatment of leukemia patients undergoing stem-cell transplantation...

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..The data challenge the notion that aGVHD is purely a Th1-type cytokine-driven response, high-lighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGVHD...

..3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions...

..Most patients now receive a trial of imatinib before proceeding to HCT...

..In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells...

..The possible role of MDR overexpression in clinical resistance to imatinib remains to be defined. We therefore confirm that imatinib should be added to the extensive list of drugs that can be affected by the MDR phenomenon...

..We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML...

..We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission...

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..Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib...

..Here we review what is known of the mechanisms underlying the evolution of chronic myeloid leukemia from a chronic phase to a blast transformation...

..Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs...

..We recognize that our recommendations are provisional and will require revision as new evidence emerges...

..At this time, children and younger adults should probably be considered for transplantation as first-line treatment...

..Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome-positive hematopoiesis to exhibitfeatures resembling normal hematopoiesis...

..Herein, we discuss the emerging strategies for circumventing resistance associated with the Bcr-Abl T315I mutation...

..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...

..Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs...

..We suggest that the acquisition of point-mutations in the tyrosine kinase domain of Bcr-Abl may cause progressive clinical resistance to STI571...

..STATE OF THE ART AND PERSPECTIVES: It is likely that the optimal usage of this important new agent will become better defined as more experience is gained...

..The presence of a donor immune response against PR1 may be advantageous and could be exploited therapeutically...

..Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity...