Posted by rob on September 28, 2009 under Uncategorized | 
We report outcomes of 932 recipients of unrelated donor peripheral blood stem cell hematopoietic cell transplantation (URD-PBSC HCT) for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome enrolled on a prospective National Marrow Donor Program trial from 1999 through 2003. Preparative regimens included myeloablative (MA; N = 611), reduced-intensity (RI; N = 160), and nonmyeloablative (NMA; N = 161). For MA recipients, CD34+ counts greater than 3.8 x 106/kg improved neutrophil and platelet engraftment, whereas improved overall survival (OS) and reduced transplant-related mortality (TRM) were seen for all preparative regimens when CD34+ cell doses exceeded 4.5 x 106/kg. Higher infused doses of CD34+ cell dose did not result in inc…
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Role of Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndrome.
Cancer Treat Res. 2009;144:1-25
Authors: Tallman MS, Mathews V, Dipersio JF
PMID: 19779880 [PubMed - as supplied by publisher]
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[Expression of DLK1 gene in acute leukemias and its function in erythroid differentiation of K562 cell line.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;34(9):886-91
Authors: Tang X, Long C, Wang C, Xiao G
Objective To determine the expression of DLK1 gene in acute leukemias (AL) and its function in erythroid differentiation of K562 cells. Methods We detected the expression of DLK1 gene in 65 different acute leukemia categories (a test group) and 34 normal bone marrow controls (a control group) with RT-PCR. DLK1 protein in 20 out of the 65 AL patients and 13 of the 34 controls was assayed by Western blot. The K562 cell line was induced to erythroid differentiation by hemin. We observed the relationship between its expression and erythroid differentiation.Results Both leukemia cells and normal marrow cells expressed DLK1. The expression of DLK1mRNA in patients in the test group was higher than that in the control group (P=0.018), while there was no significance between acute lymphoblastic leukemia and acute myelogenous leukemia (P>0.05).The expression of DLK1 mRNA in the test group at onset had no relation with the WBC and platelet count in the total peripheral blood, and the same was true for blast cell rates in bone marrow cells.The level of DLK1 protein in the test group was higher than that in the control group, which was consistent with the mRNA expression (P=0.042). The expression of DLK1 mRNA decreased gradually with K562 cells towards hemin-induced erythroid differentiation.Conclusion DLK1 gene may be involved in leukemia,but the mRNA level of DLK1 has no relation with some clinical characteristics of AL patients at onset. DLK1 may inhibit the erythroid differentiation of K562 cells.
PMID: 19779261 [PubMed - in process]
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Nonmyeloablative Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia in the Imatinib Era.
Clin Lymphoma Myeloma. 2009 Sep 1;9:S261-S265
Authors: Champlin R, Lima MD, Kebriaei P, Rondon G, Fisher T, Jabbour E, Cortés JE, Kantarjian H, Anderlini P, Alousi A, Hosing C, Shpall E, Popat U, Qazilbash M, Andersson B, Giralt S
Allogeneic stem cell transplantation (ASCT) is a potentially curative treatment for patients with chronic myelogenous leukemia (CML) and was previously considered the preferred treatment for newly diagnosed CML. The success of imatinib has changed treatment recommendations, and allogeneic transplants are now reserved for imatinib treatment failures. Previous imatinib treatment does not compromise the results of ASCT, but patients with overt transformed disease have poor results. It is unclear whether patients whose disease is considered to have failed imatinib should be referred immediately for ASCT or receive treatment with a second-generation tyrosine kinase inhibitors (TKI). Patients whose disease fails 2 TKIs should receive ASCT if possible. Nonmyeloablative preparative regimens reduce the toxicity and treatment-related mortality associated with the transplantation procedure and allow transplantations to be performed in older and medically infirm patients. This approach, including posttransplantation treatment with TKIs and donor lymphocyte infusion, produces a high fraction of durable molecular complete remissions.
PMID: 19778850 [PubMed - as supplied by publisher]
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Molecular cytogenetic characterization of variant Philadelphia translocations in chronic myeloid leukemia: genesis and deletion of derivative chromosome 9.
Cancer Genet Cytogenet. 2009 Oct;194(1):30-7
Authors: Bennour A, Sennana H, Laatiri MA, Elloumi M, Khelif A, Saad A
The mechanisms for the formation of variant Philadelphia (Ph) translocations that occur in 5-10% of patients with chronic myeloid leukemia (CML) are not fully characterized. Studies on the prognosis of these variant translocations have yielded conflicting results, especially regarding imatinib outcome and the status of deletions on the derivative chromosome 9. To shed light on these controversial subjects, we sought to analyze all variant translocation cases presented at diagnosis and identified in our institution between the years 2001 and 2008. Of 336 CML patients who presented at diagnosis and were studied by conventional cytogenetics and fluorescence in situ hybridization (FISH), 25 patients (7.44%) exhibited variant Ph-rearrangements. All chromosomes could be implicated in variant Ph rearrangements, with 32 breakpoints defined. Their distribution was located preferentially in the CG-richest regions of the genome. Deletions on der(9) were observed in 15 of the 25 cases (60%), a greater proportion in typical Ph translocations (12-15%). Both one- and two-step mechanisms were encountered in our series, as well as multiple-step mechanisms, which originate more complex rearrangements. Higher prevalence was observed for the two-step mechanism (56%). Proper assessment of the prognostic significance of variant translocations requires better categorization of these translocations based on their mechanisms of genesis and 9q34 deletion status.
PMID: 19737651 [PubMed - indexed for MEDLINE]
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Asymptomatic eosinophilic colitis in a patient with previous allogeneic bone marrow transplantation for chronic myeloid leukaemia.
Acta Gastroenterol Belg. 2009 Apr-Jun;72(2):267-8
Authors: Shindano A, Geubel A, Fervaille C, Azzouzi K
PMID: 19637788 [PubMed - indexed for MEDLINE]
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Sustained durability of responses and improved progression-free and overall survival with imatinib treatment for accelerated phase and blast crisis chronic myeloid leukemia: long-term follow-up of the STI571 0102 and 0109 trials.
Haematologica. 2009 May;94(5):743-4
Authors: Silver RT, Cortes J, Waltzman R, Mone M, Kantarjian H
PMID: 19407320 [PubMed - indexed for MEDLINE]
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The level of BCR-ABL1 kinase activity before treatment does not identify chronic myeloid leukemia patients who fail to achieve a complete cytogenetic response on imatinib.
Haematologica. 2009 Jun;94(6):861-4
Authors: Khorashad JS, Wagner S, Greener L, Marin D, Reid A, Milojkovic D, Patel H, Willimott S, Rezvani K, Gerrard G, Loaiza S, Davis J, Goldman J, Melo J, Apperley J, Foroni L
Imatinib is currently the first line therapy for newly diagnosed patients with chronic myeloid leukemia. However, 20-25% of patients do not achieve durable complete cytogenetic responses. The mechanism underlying this primary resistance is unknown, but variations in BCR-ABL1 kinase activity may play a role and can be investigated by measuring the autophosphorylation levels of BCR-ABL1 or of a surrogate target such as Crkl. In this study we used flow cytometry to investigate the in vitro inhibition of Crkl phosphorylation by imatinib in CD34(+) cells in diagnostic samples from two groups of patients distinguished by their cytogenetic response. No difference in inhibition of Crkl phosphorylation was observed in the two groups. The observation that increasing the dose of imatinib in vivo did not increase the level of cytogenetic response in some non-responders suggests that in at least a proportion of patients imatinib resistance may be due to activation of BCR-ABL1-independent pathway.
PMID: 19377081 [PubMed - indexed for MEDLINE]
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Administration of imatinib mesylate in patients with chronic myeloid leukemia with short bowel.
Leuk Lymphoma. 2009 Apr;50(4):670-2
Authors: Yamazaki R, Aisa Y, Mori T, Iketani O, Ikeda Y, Okamoto S
PMID: 19373671 [PubMed - indexed for MEDLINE]
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Presence of a new BCR-ABL kinase domain mutation, C330G in an imatinib naive patient with chronic myeloid leukemia: very low prevalence of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia from eastern India.
Leuk Lymphoma. 2009 Apr;50(4):663-6
Authors: Kuila N, Dash N, Sahoo DP, Pattnayak NC, Biswas G, Chakraborty S
PMID: 19373669 [PubMed - indexed for MEDLINE]
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Characterisation of extramedullary relapse in patients with chronic myeloid leukemia in advanced disease after allogeneic stem cell transplantation.
Leuk Lymphoma. 2009 Apr;50(4):551-8
Authors: Ocheni S, Iwanski GB, Schafhausen P, Zander AR, Ayuk F, Klyuchnikov E, Zabelina T, Fiedler W, Schnittger S, Hochhaus A, Brümmendorf TH, Kröger N, Bacher U
Recently, higher extramedullary relapse rates following allogeneic stem cell transplantation (SCT) in myeloid malignancies were reported e.g. because of selection of poor-risk patients. We analysed five consecutive patients with post-transplant extramedullary relapse of chronic myeloid leukemia (CML) out of a total of 24 patients (21%) undergoing allo-SCT. All five patients with extramedullary relapse had clonal evolution and a history of blast phase (BP). In particular, 56% of the patients in BP had extramedullary relapse with no extramedullary relapse in patients with chronic/accelerated phase. Most frequent manifestation sites were the skeletal system, the muscles/subcutaneous tissue and the central nervous system. In one case chloroma was mimicking myositis of the lower limbs. Combined approaches were performed including irradiation (n = 4), chemotherapy (n = 2), IM (n = 2), dasatinib (n = 4), nilotinib (n = 1), a novel aurora-kinase-inhibitor (n = 1), donor lymphocytes (n = 2) or a second allo-SCT (n = 2). Transient response was achieved in one case, stable partial remissions in two cases, whereas two cases were refractory. Research should focus on prospective studies aiming to improve treatment of extramedullary relapse in stem cell recipients with CML with a special focus on the role of second generation tyrosine kinase inhibitors.
PMID: 19373652 [PubMed - indexed for MEDLINE]
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Extramedullary relapse of chronic myeloid leukemia in blast crisis: more questions than answers.
Leuk Lymphoma. 2009 Apr;50(4):517-8
Authors: Ross DM
PMID: 19373644 [PubMed - indexed for MEDLINE]
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