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Chronic Myeloid Leukaemia News Headlines
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All Recent Chronic Myeloid Leukaemia News Headlines |
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Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukaemia
This study strengthens the hypothesis that acute leukaemias give rise to more profound cytopenias, affecting more cell lines, than chronic leukaemias. (Source: Veterinary and Comparative Oncology)...
POSTED 06/30/2009 at 06:00 PM --
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Phase III Study of Dasatinib Once Daily for Imatinib-Resistant CML
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
In patients with accelerated-phase chronic myeloid leukemia who are intolerant of or resistant to imatinib, once-daily dasatinib 140... (Source: OncologySTAT Journal Scans)...
POSTED 06/30/2009 at 09:58 AM --
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88% Of Chronic Phase Patients With Ph+ CML Who Are Intolerant Or Resistant To Glivec Are Still Alive At 2 Years When Treated With Tasigna
New data show that at 24 months, patients in the chronic phase of Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML) who are intolerant or resistant to current first-line therapy (Glivec) experienced a rapid response and significant reduction in leukaemia burden when treated with 400mg Tasigna twice-daily1. (Source: Health News from Medical News Today)...
POSTED 06/30/2009 at 05:00 AM --
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Analysis of the quality of reporting of randomized controlled trials in acute and chronic myeloid leukemia, and myelodysplastic syndromes as governed by the CONSORT statement.
CONCLUSIONS: Quality of reporting in RCTs focusing on myeloid malignancies remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.
PMID: 19523596 [PubMed - in process] (Source: Annals of Epidemiology)...
POSTED 06/27/2009 at 09:05 PM --
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New experimental and theoretical investigations of hematopoietic stem cells and chronic myeloid leukemia.
We report on a focused workshop of The Leukemia and Lymphoma Society that was held at Goldsmiths, University of London in 2008. During this workshop we discussed new clinical and experimental data in chronic myeloid leukemia (CML) research, particularly focusing on the validity (or otherwise) of corresponding mathematical models and simulations. We were specifically interested in whether the models could shed light on any of the fundamental mechanisms underlying this disease. Moreover, we were aiming to form a new community of clinicians and modelers looking at this disease and to define a common language and theoretical framework within which collaboration could flourish. The workshop showed the role that models can play, not just in trying to fit to existing data or predicting what indiv......
POSTED 06/27/2009 at 12:07 PM --
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Cutaneous lichenoid eruption caused by imatinib mesylate in a Japanese patient with chronic myeloid leukaemia.
Authors: Kawakami T, Kawanabe T, Soma Y
PMID: 19479144 [PubMed - in process] (Source: Acta Derm Venereol A...)...
POSTED 06/27/2009 at 10:28 AM --
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Facts and uncertainties in monitoring treatment response in chronic myeloid leukaemia
Abstract: For patients with chronic myeloid leukaemia (CML), current guidelines advocate frequent monitoring using haematological, cytogenetic, and molecular methods, and these have been used to set targets for disease responses at various time points. Recent clinical data, however, have provided new information on responses to treatment with tyrosine kinase inhibitors, which may have implications for how patients should be monitored. Topics of debate include whether time to complete cytogenetic response (CCyR) is clinically important, what benefit is derived from achieving a major molecular response in patients who have achieved CCyR, and what prognostic implications are associated with developing different types of BCR-ABL mutation. Here, current questions relating to CML monitoring are ......
POSTED 06/26/2009 at 09:24 AM --
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Structural modeling of V299L and E459K Bcr-Abl mutation, and sequential therapy of tyrosine kinase inhibitors for the compound mutations
Abstract: Sequential treatment with different tyrosine kinase inhibitors (TKIs) is one of the strategies for handling chronic myeloid leukemia (CML) in which dynamic change in Bcr-Abl kinase domain mutation is often an obstacle faced during TKI therapy. Here we report successful sequential therapy with different TKIs for the CML patient harboring V299L and E459K compound mutations. Molecular monitoring including quantitative analysis of BCR-ABL transcript level and mutation analysis were performed regularly for successful treatment. Additionally a drug-target complex was structurally modeled to investigate influence of amino acid substitutions on drug resistance, and to choose alternative TKI in sequential therapy, suggesting protein structural modeling can be useful approach in selecting ......
POSTED 06/26/2009 at 09:24 AM --
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Myelodysplastic syndrome appearing during imatinib mesylate therapy in a patient with GIST
We report here a case of refractory cytopenia with mutilineage dysplasia (RAEB-1) with monosomy 7 which rapidly transformed into AML in a patient with GIST during imatinib treatment. (Source: Leukemia Research)...
POSTED 06/26/2009 at 09:24 AM --
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Successful Nilotinib therapy in an imatinib-resistant chronic myeloid leukemia patient displaying an intron-derived insertion/truncation mutation in the BCR–ABL kinase domain
The introduction of imatinib mesylate (IM) has produced major advances in the treatment of chronic myeloid leukemia (CML) resulting in high rates of complete hematologic and cytogenetic responses (CHR and CCyR) after 5 years of treatment . However, 17% of chronic phase (CP) patients display primary resistance to IM or acquire secondary resistance to the drug, and the incidence of resistance increases in the more advanced stages of the disease . Current studies indicate that multiple mechanisms contribute to IM failure, including persistence of CML quiescent stem cells, BCR–ABL amplification and BCR–ABL kinase domain mutations (KDMs) . On these bases, several strategies have been developed to overcome the issue of IM resistance, including IM dose escalation, combination treatments or no......
POSTED 06/26/2009 at 09:24 AM --
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CD8+ memory T cells predominate over naïve T cells in therapy-free CML patients with sustained major molecular response
While imatinib mesylate (IM) is currently the gold standard for treating patients with chronic myeloid leukemia (CML) in the chronic phase (CP), the leukemia-initiating stem cells of CML are resistant to IM and the majority of patients who stop it after achieving a complete molecular response (CMR) are reported to relapse , suggesting that CML is unlikely to be cured by IM monotherapy. However, recent data indicate that CMR can be sustained after discontinuation of IM, particularly in patients with a history of prolonged interferon-alpha (IFN) therapy . We analyzed peripheral blood lymphocyte subsets in nine CML patients who discontinued therapy after showing a major molecular response (MMR) for more than 2 years: four patients relapsed and the remaining five patients remain in MMR without......
POSTED 06/26/2009 at 09:24 AM --
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JAK2 mutation and atypical chronic myeloid leukemia
F. Fend et al. describe a well characterized series of 11 patients affected by atypical chronic myeloid leukemia (aCML). In 9 patients the presence of JAK2-V617F mutation was examined by a retrospective analysis of archival specimens and was negative in all cases. (Source: Leukemia Research)...
POSTED 06/26/2009 at 09:24 AM --
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Bacterial pneumonia following bone marrow transplantation: HRCT findings
CONCLUSIONS: The most common HRCT findings in our patient sample were air-space consolidation, small centrilobular nodules and ground-glass opacities, most often in the central and peripheral regions of the middle and lower lung zones.OBJETIVO: Descrever os achados de TCAR em pacientes com pneumonia bacteriana após transplante de medula óssea (TMO). MÉTODOS: Estudo retrospectivo com 30 pacientes diagnosticados com pneumonia bacteriana, documentada com TCAR do tórax realizada em até 24 h do início dos sintomas, e com diagnóstico comprovado com base em cultura positiva de escarro ou de aspirado brônquico associada à cultura positiva de líquido pleural ou de sangue dentro de uma semana após o início dos sintomas. Foram avaliados 20 pacientes masculinos e 10 femininos, com mediana ......
POSTED 06/25/2009 at 03:23 AM --
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Evaluation diagnosis of minimal residual disease in chronic myeloid leukemia by Real-Time PCR
A leucemia mielóide crônica (LMC) representa 15% das leucemias e apresenta três fases: crônica, acelerada e crise blástica. A partir da análise citogenética, pode ser identificado o cromossomo Philadelphia, característico da LMC. O transplante de células-tronco é o único tratamento curativo, mas é acompanhado de altas taxas de morbimortalidade, dificultando sua aplicação. A doença residual mínima é de grande importância para avaliar a resposta ao tratamento, tanto na verificação de doença residual, quanto na identificação de pacientes com alto risco de recaída. Muitas técnicas específicas têm sido introduzidas para detectar as translocações ou os produtos do cromossomo Philadelphia. A mais sensível é a Real-Time PCR, que detecta uma célula leucêmica em 10(5......
POSTED 06/25/2009 at 03:06 AM --
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Abnormal centrosome-centriole cycle in chronic myeloid leukaemia?
This study showed, for the first time, that p210BCR-ABL1 and p145ABL1 are both centrosome-associated proteins, as demonstrated by co-immunoprecipitation with the pericentriolar protein, pericentrin. Furthermore, when CML cells were treated with imatinib there was a 55% and 20% reduction of p210BCR-ABL1 and p145ABL1 binding to pericentrin, respectively. Cell lines expressing p210BCR-ABL1 and primary CD34+ cells from CML patients exhibited more numerical and structural centrosomal abnormalities than p210BCR-ABL1 negative cells. Primary cells from CML blast crisis (BC) patients exhibited a distinctive amorphous staining pattern of pericentrin compared to normal and CML chronic phase (CP) patients, suggesting a possible defect in pericentrin localisation at the centrosomes. Proteins, such as a......
POSTED 06/24/2009 at 06:00 PM --
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Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy
Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilities of eventually achieving a cytogenetic response versus progressing. We analyzed the probability of achieving a CCyR, major molecular response, and progression in 258 patients with chronic myeloid leukemia in early chronic phase at 3, 6, and 12 months from imatinib start. The initial imatinib dose was 800 mg/day in 208 (81%) and 400 mg/day in 50 (19%) patients. For patients not in CCyR, the probability of achieving CCyR (P = .002) or major molecular response (P = .004) significantly decreased, whereas the risk of progression increased (P = .16) at each time point. Patients with a BCR-ABL1/ABL1 ratio greater than 1% to 10% after 3 months of imatinib had a 92% probability of achieving CCyR with c......
POSTED 06/17/2009 at 06:00 PM --
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Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily
In patients with chronic-phase chronic myeloid leukemia (CP-CML), imatinib resistance is of increasing importance. Imatinib dose escalation was the main treatment option before dasatinib, which has 325-fold more potent inhibition than imatinib against unmutated Bcr-Abl in vitro. Data with a minimum of 2 years of follow-up were available for the current study of dasatinib and high-dose imatinib in CP-CML resistant to imatinib at daily doses from 400 mg to 600 mg.A phase 2, open-label study was initiated of 150 patients with imatinib-resistant CP-CML who were randomized (2:1) to receive either dasatinib 70 mg twice daily (n = 101) or high-dose imatinib 800 mg (400 mg twice daily; n = 49).At a minimum follow-up of 2 years, dasatinib demonstrated higher rates of complete hematologic response (......
POSTED 06/16/2009 at 06:00 PM --
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Synthetic tumor-specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease
Imatinib is the current standard frontline therapy for chronic myelogenous leukemia (CML). In the majority of patients, imatinib induces a complete cytogenetic response (CCyR); however, complete molecular responses are infrequent. The Bcr-Abl fusion creates a unique sequence of amino acids that could constitute a target for immunomodulation.A mixture of heteroclitic and native peptides derived from both b3a2 and b2a2 sequences was used to vaccinate patients with CML in CCyR who were receiving imatinib therapy and who had stable Bcr-Abl transcript levels.Ten patients were enrolled, all with b2a2 transcripts (including 2 patients who had coexpression of b2a2 and b3a2). Patients had received imatinib for a median of 62 months. Three of 10 patients achieved 1-log reduction in Bcr-Abl transcrip......
POSTED 06/16/2009 at 06:00 PM --
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Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3.
Authors: Masson K, Rönnstrand L
Signal transduction in response to growth factors is a strictly controlled process with networks of feedback systems, highly selective interactions and finely tuned on-and-off switches. In the context of cancer, detailed signaling studies have resulted in the development of some of the most frequently used means of therapy, with several well established examples such as the small molecule inhibitors imatinib and dasatinib in the treatment of chronic myeloid leukemia. Impaired function of receptor tyrosine kinases is implicated in various types of tumors, and much effort is put into mapping the many interactions and downstream pathways. Here we discuss the hematopoietic growth factor receptors c-Kit and Flt3 and their downstream signaling in normal a......
POSTED 06/16/2009 at 06:00 PM --
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ChemGenex's Omacetaxine May Provide First Viable Treatment Option For Highly Resistant Form Of CML
MELBOURNE, Australia, and MENLO PARK, California -- ChemGenex Pharmaceuticals Limited (ChemGenex) announced that the latest data from its pivotal study of omacetaxine in patients with T315I-positive chronic myeloid leukemia (CML) was the subject of an oral presentation and discussion today at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida. The open label Phase 2/3 study (CGX-635-CML-202) investigated the use of omacetaxine, administered subcutaneously in CML patients who had failed imatinib and who have the highly drug resistant T315I kinase domain mutation. Dr. Jorge Cortes, MD, Professor of Medicine and Deputy Chair in the Department of Leukemia at The University of Texas, MD Anderson Cancer Ce... (Source: Cancercompass News: Other Cancer)...
POSTED 06/13/2009 at 12:00 AM --
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