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Chronic Myeloid Leukemia (chronic + myeloid_leukemia)
Terms modified by Chronic Myeloid Leukemia Selected AbstractsHematological malignancies in the island of Sardinia, 1974,1993: age and sex distributions and temporal changes in incidenceHEMATOLOGICAL ONCOLOGY, Issue 3 2004G. Broccia Abstract We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974,1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984,1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia. Copyright © 2005 John Wiley & Sons, Ltd. [source] A BCR,JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2005Frank Griesinger Chronic myeloid leukemia (CML) is characterized by the presence of a t(9;22)(q34;q11.2), which leads to the well-known BCR,ABL1 fusion protein. We describe a patient who was diagnosed clinically with a typical CML but on cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion partner of BCR in this case. The BCR,JAK2 fusion protein contains the coiled-coil dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2. The patient's disease did not respond to Imatinib, and this unresponsiveness was most likely a result of the BCR,JAK2 fusion protein. © 2005 Wiley-Liss, Inc. [source] XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Vicent M. Guillem Chronic myeloid leukemia (CML) is driven by the BCR-ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR-ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polimorfisms (SNPs) on the nucleotide excision repair (NER) genes (ERCC2-ERCC8, RPA1-RPA3, LIG1, RAD23B, XPA, XPC) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild-type haplotype (499C-939A) was associated with a better response to imatinib. Moreover, the 5-year failure free survival for CA carriers was significantly better than that of the non-CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb ,11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5,16.1) or a non-CA XPC haplotype (OR = 4.1, 95% CI = 1.6,10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Chronic myeloid leukemia in a patient with chronic idiopathic thrombocytopenic purpura: Rapid response to imatinib mesylate (STI571)PEDIATRIC BLOOD & CANCER, Issue 2 2003Shinsaku Imashuku MD No abstract is available for this article. [source] Technical aspects and clinical applications of measuring BCR-ABL1 transcripts number in chronic myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Letizia Foroni Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a triphasic clinical course, the morphologic expansion of a terminally differentiated myeloid cell and the presence of the BCR-ABL1 fusion gene, the hallmark of CML. The fusion gene is usually, but not always, associated with a Philadelphia chromosome, the result of a reciprocal exchange of genetic material between chromosome 22 and chromosome 9, which leads to the production of the activated BCR-ABL1 gene and oncoprotein. The breakpoint in the BCR gene occurs commonly downstream of exons e13 or e14 (M-BCR) and less frequently downstream of exons e1 and e2 (m- BCR). Less than 1% of cases carry a breakpoint downstream of exon 6 or 8 ("variant fusion genes") or exon 19 (,- BCR). Breakpoints in the ABL1 gene cluster upstream of exon a2 (or of exon a3 in less than 5% of patients with CML). Conventional cytogenetic, fluorescence in situ hybridization, and molecular testing for the BCR-ABL1 fusion gene are key investigations for the diagnosis and monitoring of CML. Treatment using tyrosine kinase inhibitors has revolutionized the management of CML with hematologic and cytogenetic response within 12,18 months observed in >85% of patients. Nevertheless, between 15 and 20% of patients may evolve to blastic phase. Measurement of low level or "minimal" residual disease using molecular tests is becoming the gold-standard approach to measure response to therapy due to its higher sensitivity compared to other routine techniques. The technical aspects and clinical applications of molecular monitoring will be the main focus of this article. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal originGENES, CHROMOSOMES AND CANCER, Issue 10 2010Jan Zuna The ETV6/ABL1 (TEL/ABL) fusion gene is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1 -positive hematological malignancy have been published, diagnosed with chronic myeloid leukemia, other types of chronic myeloproliferative neoplasm, acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This study reports three new cases (aged 8 months, 5 years, and 33 years) of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed ALL patients (335 children and 57 adults). A thorough review of the literature and an analysis of all published data, including the three new cases, suggest poor prognosis of ETV6/ABL1 -positive acute leukemias. The course of the disease in the two pediatric patients is characterized by minimal residual disease monitoring, using quantification of both the ETV6/ABL1 transcript and immunoreceptor gene rearrangements. Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1 -positive disease. Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally. © 2010 Wiley-Liss, Inc. [source] A BCR,JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2005Frank Griesinger Chronic myeloid leukemia (CML) is characterized by the presence of a t(9;22)(q34;q11.2), which leads to the well-known BCR,ABL1 fusion protein. We describe a patient who was diagnosed clinically with a typical CML but on cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion partner of BCR in this case. The BCR,JAK2 fusion protein contains the coiled-coil dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2. The patient's disease did not respond to Imatinib, and this unresponsiveness was most likely a result of the BCR,JAK2 fusion protein. © 2005 Wiley-Liss, Inc. [source] Genomic imbalances in CML blast crisis: 8q24.12,q24.13 Segment identified as a common region of over-representationGENES, CHROMOSOMES AND CANCER, Issue 4 2003Susan M. Gribble The acute phase of chronic myeloid leukemia (CML) is accompanied by secondary chromosomal changes. The additional changes have a non-random pattern; however, highly abnormal (marker) chromosomes are reported in some 20% of abnormal karyotypes. These marker chromosomes have proved to be beyond the resolution of conventional G-banding analysis. We used molecular cytogenetic techniques to determine the structure of complex chromosome markers in 10 CML-derived cell lines after our investigations of CML patients in blast crisis. Multicolor fluorescence in situ hybridization identified a multitude of structural chromosome aberrations. In addition, genomic gains identified by comparative genomic hybridization (CGH) were mapped to highly complex marker chromosomes in more than one cell line. The most common genomic loss detected by CGH affected chromosome 9, whereas the most common genomic gains affected, in order of frequency, the sequences of 8q, 6, and 13q. The smallest discrete amplification on 8q was identified in cell line MEG-01. This amplicon contains sequences represented by the marker D8S263/RMC08P029 but did not contain the proximal MYC gene or a more distal marker, D8S256/RMC08P025. We determined the size of the amplicon to be less than the chromosome segment 8q24.12,q24.13. The use of region- and locus-specific probes to analyze the organization of highly complex marker structures aided the identification of preferentially amplified genomic regions. The resultant amplifications could harbor gene(s) driving disease progression. © 2003 Wiley-Liss, Inc. [source] Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 1 2001Simone Metzke-Heidemann We describe the cases of two patients with Philadelphia chromosome,positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL -positive CML. © 2001 Wiley-Liss, Inc. [source] NF-,B inhibition triggers death of imatinib-sensitive and imatinib-resistant chronic myeloid leukemia cells including T315I Bcr-Abl mutantsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Nadia Lounnas Abstract The Bcr-Abl inhibitor imatinib is the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Nevertheless, resistance to imatinib emerges as CML progresses to an acute deadly phase implying that physiopathologically relevant cellular targets should be validated to develop alternative therapeutic strategies. The NF-,B transcription factor that exerts pro-survival actions is found abnormally active in numerous hematologic malignancies. In the present study, using Bcr-Abl-transfected BaF murine cells, LAMA84 human CML cell line and primary CML, we show that NF-,B is active downstream of Bcr-Abl. Pharmacological blockade of NF-,B by the IKK2 inhibitor AS602868 prevented survival of BaF cells expressing either wild-type, M351T or T315I imatinib-resistant mutant forms of Bcr-Abl both in vitro and in vivo using a mouse xenograft model. AS602868 also affected the survival of LAMA84 cells and of an imatinib-resistant variant. Importantly, the IKK2 inhibitor strongly decreased in vitro survival and ability to form hematopoietic colonies of primary imatinib resistant CML cells including T315I cells. Our data strongly support the targeting of NF-,B as a promising new therapeutic opportunity for the treatment of imatinib resistant CML patients in particular in the case of T315I patients. The T315I mutation escapes all currently used Bcr-Abl inhibitors and is likely to become a major clinical problem as it is associated with a poor clinical outcome. © 2009 UICC [source] Pml and TAp73 interacting at nuclear body mediate imatinib-induced p53-independent apoptosis of chronic myeloid leukemia cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Jin-Hwang Liu Abstract Bcr-abl signals for leukemogenesis of chronic myeloid leukemia (CML) and activates ras. Since the function of promyelocytic leukemia protein (pml) is provoked by ras to promote apoptosis and senescence in untransformed cells, the function is probably masked in CML. Imatinib specifically inhibits bcr-abl and induces apoptosis of CML cells. As reported previously, p53wild CML was more resistant to imatinib than that lacking p53. Here, we searched for an imatinib-induced p53 independent proapoptotic mechanism. We found imatinib up-regulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), checkpoint kinase 2 (chk2) and transactivation-competent (TA) p73; expression of pml and bax; formation of PML-nuclear body (NB); and co-localization of TAp73/PML-NB in p53-nonfunctioning K562 and p53mutant Meg-01 CML cells, but not in BCR-ABL - HL60 cells. In K562 cells, with short interfering RNAs (siRNAs), knockdown of pml led to dephosphorylation of TAp73. Knockdown of either pml or TAp73 abolished the imatinib-induced apoptosis. Inhibition of p38 MAPK with SB203580 led to dephosphorylation of TAp73, abolishment of TAp73/PML-NB co-localization, and the subsequent apoptosis. Conversely, interferon ,-2a (IFN,), which increased phosphrylated TAp73 and TAp73/PML-NB co-localization, increased additively apoptosis with imatinib. The imatinib-induced TAp73/PML-NB co-localization was accompanied by co-immpunoprecipitation of TAp73 with pml. The imatinib-induced co-localization was also found in primary CML cells from 3 of 6 patients, including 2 with p53mutant and one with p53wild. A novel p53-independent proapoptotic mechanism using p38 MAPK /pml/TAp73 axis with a step processing at PML-NB and probably with chk2 and bax being involved is hereby evident in some imatinib-treated CML cells. © 2009 UICC [source] Overweight and obesity and incidence of leukemia: A meta-analysis of cohort studiesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2008Susanna C. Larsson Abstract We conducted a meta-analysis to summarize the available evidence from cohort studies on the association between excess body weight and incidence of leukemia. Studies were identified by searching the MEDLINE and EMBASE databases (1966,July 2007) and by examining the references of retrieved articles. A random-effects model was used to combine the results from individual studies. We identified 9 cohort studies with data on body mass index (BMI) or obesity in relation to incidence of leukemia. Compared with nonoverweight individuals (BMI < 25 kg/m2), the summary relative risks (RRs) of leukemia were 1.14 [95% confidence interval (CI), 1.03,1.25] for overweight individuals (BMI 25,30 kg/m2) and 1.39 (95% CI, 1.25,1.54) for obese (BMI , 30 kg/m2) individuals. On a continuous scale, a 5 kg/m2 increase in BMI was associated with a 13% increased risk of leukemia (RR, 1.13; 95% CI, 1.07,1.19). In a meta-analysis of 4 studies reporting results on subtypes of leukemia, the summary RRs associated with obesity were 1.25 (95% CI, 1.11,1.41) for chronic lymphocytic leukemia, 1.65 (95% CI, 1.16,2.35) for acute lymphocytic leukemia, 1.52 (95% CI, 1.19,1.95) for acute myeloid leukemia and 1.26 (95% CI, 1.09,1.46) for chronic myeloid leukemia. This meta-analysis indicates that excess body weight is associated with an increased risk of developing leukemia. © 2007 Wiley-Liss, Inc. [source] Tyrosine-phosphorylated STAT5 accumulates on podosomes in Hck-transformed fibroblasts and chronic myeloid leukemia cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007Renaud Poincloux In chronic myeloid leukemia (CML), the transforming activity of Bcr/Abl involves constitutive activation of the phagocyte specific Src-family tyrosine kinase Hck, which in turn directly activates the signal transducer and activator of transcription 5 (STAT5). The effect of Hck on STAT5 was first explored independently of Bcr/Abl by expressing the constitutively active Hck mutant (Hckca) in MEF3T3-TetOff fibroblasts. As previously reported, Hckca -expressing cells form podosomes which are actin-rich structures involved in trans-tissular cell migration and found in the few cell types able to cross anatomic boundaries. We demonstrated that in these cells, the tyrosine-phosphorylated form of STAT5 (PY-STAT5) increased and preferentially localized on podosomes together with Hck, instead of translocating to the nucleus as observed with conventional stimuli such as IFN,. To examine whether similar results were obtained in the presence of Bcr/Abl, the CML cell line K562 was used. We observed that (i) podosomal structures are present in these cells in contrast to Bcr/Abl-negative leukemic cells, (ii) podosome formation was inhibited by Bcr/Abl- and Src-kinase inhibitors, and (iii) PY-STAT5 mainly colocalized with Hck on these structures. The presence of podosomes was not sufficient to trap STAT5 since in normal macrophages which spontaneously form podosomes and express regulated Hck, PY-STAT5 is in the nucleus. In conclusion, this is the first report showing that PY-STAT5 associates to podosomes in a process dependent on constitutive activation of Hck. We propose that STAT5, previously classified as a transcription factor, could play another role outside the nucleus, elicited by the Bcr/Abl-Hck transforming pathway. J. Cell. Physiol. 213: 212,220, 2007. © 2007 Wiley-Liss, Inc. [source] BCR gene disruption in a pilomyxoid astrocytomaNEUROPATHOLOGY, Issue 5 2006Bárbara Meléndez We report here a 4-month-old child with a large, solid enhancing mass involving predominantly the suprasellar and diencephalic regions, with extension of both hemispheres. The patient underwent partial resection of the mass by right temporal craniotomy. Histological diagnosis was of a low-grade glioma consistent with pilomyxoid astrocytoma. Cytogenetic analyses revealed an insertion on chromosome 17 that involved disruption of the BCR gene. This finding suggests a possible rearrangement of this gene that could act in a similar way to chronic myeloid leukemia with formation of a chimeric tyrosine kinase protein. This study may suggest the use of inhibitors of tyrosine kinase proteins as an alternative treatment approach in cases of refractory or disseminated pilocytic astrocytomas. [source] XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Vicent M. Guillem Chronic myeloid leukemia (CML) is driven by the BCR-ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR-ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polimorfisms (SNPs) on the nucleotide excision repair (NER) genes (ERCC2-ERCC8, RPA1-RPA3, LIG1, RAD23B, XPA, XPC) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild-type haplotype (499C-939A) was associated with a better response to imatinib. Moreover, the 5-year failure free survival for CA carriers was significantly better than that of the non-CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb ,11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5,16.1) or a non-CA XPC haplotype (OR = 4.1, 95% CI = 1.6,10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] ASH 2009 meeting report,Top 10 clinically oriented abstracts in chronic myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Amber Fullmer First page of article [source] Complete response to imatinib mesylate treatment in a 12-month-old patient with chronic myeloid leukemiaPEDIATRIC BLOOD & CANCER, Issue 5 2008Alejandro Mauricio Arancibia MD No abstract is available for this article. [source] Hearing loss in chronic myeloid leukemiaPEDIATRIC BLOOD & CANCER, Issue 1 2005Rahul Naithani MBBS Abstract A 12-year-old girl presented with abdominal pain, fever, and hearing impairment of 6 months duration. She had massive hepatosplenomegaly and anemia. On the basis of her peripheral blood and bone marrow findings, she was diagnosed as chronic myeloid leukemia (CML) in chronic phase. Her hearing was assessed by brainstem evoked responses (BERA), which showed objective improvement in hearing with hydroxyurea. The rare occurrence of deafness in CML is reviewed and possible pathogenesis is discussed. Pediatr Blood Cancer 2005; 45: 54,56. © 2005 Wiley-Liss, Inc. [source] Technical aspects and clinical applications of measuring BCR-ABL1 transcripts number in chronic myeloid leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Letizia Foroni Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a triphasic clinical course, the morphologic expansion of a terminally differentiated myeloid cell and the presence of the BCR-ABL1 fusion gene, the hallmark of CML. The fusion gene is usually, but not always, associated with a Philadelphia chromosome, the result of a reciprocal exchange of genetic material between chromosome 22 and chromosome 9, which leads to the production of the activated BCR-ABL1 gene and oncoprotein. The breakpoint in the BCR gene occurs commonly downstream of exons e13 or e14 (M-BCR) and less frequently downstream of exons e1 and e2 (m- BCR). Less than 1% of cases carry a breakpoint downstream of exon 6 or 8 ("variant fusion genes") or exon 19 (,- BCR). Breakpoints in the ABL1 gene cluster upstream of exon a2 (or of exon a3 in less than 5% of patients with CML). Conventional cytogenetic, fluorescence in situ hybridization, and molecular testing for the BCR-ABL1 fusion gene are key investigations for the diagnosis and monitoring of CML. Treatment using tyrosine kinase inhibitors has revolutionized the management of CML with hematologic and cytogenetic response within 12,18 months observed in >85% of patients. Nevertheless, between 15 and 20% of patients may evolve to blastic phase. Measurement of low level or "minimal" residual disease using molecular tests is becoming the gold-standard approach to measure response to therapy due to its higher sensitivity compared to other routine techniques. The technical aspects and clinical applications of molecular monitoring will be the main focus of this article. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Vitiligo-Like Lesions and Diffuse Lightening of the Skin in a Pediatric Patient Treated with Imatinib Mesylate: A Noninvasive Colorimetric AssessmentPEDIATRIC DERMATOLOGY, Issue 2 2006Valeria Brazzelli M.D. It acts as a potent and selective inhibitor of BCR-ABL tyrosine kinase. It also inhibits both c-kit and platelet-derived growth factor receptor tyrosine kinases. Hypopigmentation of the skin in patients receiving this drug has been recently reported. We report a 17-year-old Caucasian patient affected by chronic myeloid leukemia in therapy with imatinib mesylate who developed hypopigmented vitiligo-like patches and generalized lightening of the skin. In order to evaluate the lightening observed clinically, we measured the progressive skin color hypopigmentation by using a colorimeter over several months. The colorimetric evaluation confirmed the generalized and gradual lightening of patient's skin over treatment with imatinib mesylate. We believe that this is the first reported instance of vitiligo-like lesions in a pediatric patient treated with imatinib mesylate, and the second in a Caucasian patient. [source] First-line therapy for chronic myeloid leukemia: Past, present, and future,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Carolina Pavlovsky The development of Bcr-Abl tyrosine kinase inhibitors has dramatically changed the prognosis of patients with newly diagnosed chronic myeloid leukemia (CML). Standard-dose imatinib (400 mg/day in chronic phase, 600 mg/day in advanced CML) now dominates the management of this disease, producing considerably higher hematologic, cytogenetic, and molecular response rates than seen with previous drug therapies. However, although many patients respond well to standard-dose imatinib initially, some patients do not achieve adequate levels of response or discontinue therapy because of resistance. One approach to improving treatment response with first-line imatinib may be to increase the imatinib dose (800 mg/day), although recent trial data indicate that overall increases in response rates may be modest. Newer Bcr-Abl tyrosine kinase inhibitors can induce responses in patients with all phases of imatinib-resistant CML, even those with imatinib-resistant mutations in the BCR-ABL gene. Furthermore, in initial studies, first-line dasatinib or nilotinib treatment has produced response rates that compare favorably with historical controls treated with imatinib, although confirmation is required from head-to-head clinical trials. Future clinical approaches may include drug combinations, which may allow quiescent leukemia stem cells to be eradicated. Further improvements in drug treatment for first-line CML are expected during the next few years. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Juvenile myelomonocytic leukemia with t(7;11)(p15;p15) and NUP98-HOXA11 fusion,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Yoko Mizoguchi The t(7;11)(p15;p15) translocation has been reported as a rare and recurrent chromosomal abnormality in acute myeloid leukemia (AML) patients. The NUP98-HOXA9 fusion gene with t(7;11)(p15;p15) was identified and revealed to be essential for leukemogenesis and myeloproliferative disease. To date, t(7;11)(p15;p15) with NUP98-HOXA11 fusion has been reported only in one case of ph-negative chronic myeloid leukemia (CML). Here, we report a case of a 3-year-old girl with juvenile myelomonocytic leukemia (JMML) carrying t(7;11)(p15;p15) abnormality with NUP98-HOXA11 fusion. AML chemotherapy followed by bone marrow transplantation (BMT) was found to be effective in treating this disorder, and she remains in complete remission for 3 years after BMT. We suggest the possibility that AML chemotherapy might be effective for treating JMML with t(7;11)(p15;p15) abnormality and NUP98-HOXA11 fusion. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Hepatitis B immunoglobulin in combination with lamivudine for prevention of hepatitis B virus reactivation in children undergoing bone marrow transplantationPEDIATRIC TRANSPLANTATION, Issue 8 2006Betul Tavil Abstract:, There is little information in literature about the use of hepatitis B immunoglobulin (HBIg) in recipients of bone marrow transplantation (BMT). Here, we report two children who received IV HBIg (Hepatect-CP) and lamivudine treatment during BMT course for either patient or donor hepatitis B virus (HBV) viremia. A four-year-old girl underwent a fully human leukocyte antigen-matched allogeneic BMT for thalassemia major from her mother positive for hepatitis B surface antigen (HBsAg). A 12-yr-old boy with chronic myeloid leukemia, positive for HBsAg and HBV-DNA received a fully HLA-matched allogeneic BMT from his sister in the first chronic phase of the disease. HBIg was successfully used in both cases to prevent HBV reactivation of the recipients. The results of our observations are encouraging and we suggest that HBIg in combination with lamivudine may be used in such cases especially in post-transplant early period to prevent HBV reactivation. [source] Philadelphia-negative acute myeloid leukemia with new chromosomal abnormalities developing after first-line imatinib treatment for chronic phase chronic myeloid leukemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008Carmen Fava No abstract is available for this article. [source] Monosomy 7 with severe myelodysplasia developing during imatinib treatment of Philadelphia-positive chronic myeloid leukemia: Two cases with a different outcomeAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2007José-Tomás Navarro Chromosomal abnormalities in Ph-negative metaphases from patients with chronic myeloid leukemia (CML) treated with imatinib have been described in some cases. Trisomy 8 is the most frequent, but monosomy 7 has also been described. However, the association of these chromosomal alterations with myelodysplasia has been scarcely reported. We report the appearance of monosomy 7 in Ph-negative cells, associated with severe dysplasia, in two patients with CML treated with imatinib, with a different outcome: one with a transient evolution and the other evolving to acute myeloid leukemia. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Disseminated extramedullary myeloid tumor of the gallbladder without involvement of the bone marrowAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2007Angela N. Bartley Abstract Extramedullary myeloid tumors (myeloid sarcomas) are rare neoplasms that are composed of myeloid precursors. They usually arise concurrently with a diagnosis of acute myeloid leukemia, chronic myeloid leukemia, or other myeloproliferative disorders. They may also indicate relapsing disease in a patient with a prior history of leukemia or myeloproliferative disorder. We present our findings of a 63-year-old female diagnosed with extramedullary myeloid tumor first presenting in the gallbladder. She subsequently developed respiratory failure; pre- and postmortem bone marrow studies were negative for leukemia by morphology, flow cytometry, and karyotypic analysis. However, the myeloid neoplasm was disseminated throughout most of her remaining organs. Immunohistochemical stains of the cells indicated a neoplasm of myelomonocytic derivation (CD4, CD43, CD45, CD68, myeloperoxidase, and lysozyme positive). To our knowledge, this is the first report of an extramedullary myeloid neoplasm of the gallbladder with disseminated disease without involvement of the bone marrow. Am. J. Hematol., 2006. © Wiley-Liss, Inc. [source] Acute promyelocytic leukemia developing in untreated essential thrombocythemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2002Naoaki Sato Abstract We describe a patient with untreated essential thrombocythemia (ET) who developed microgranular variant of acute promyelocytic leukemia, 9 years after the initial diagnosis of ET. He achieved complete remission (CR) but relapsed 11 months later. After achieving the second CR, he received peripheral stem cell transplantation from his HLA complete-matched sibling. Five months after the transplantation, he relapsed again with meningeal infiltration of leukemic cells. In this paper, we review cases of promyelocytic transformation of myeloproliferative diseases (MPD) other than chronic myeloid leukemia (CML). To our knowledge, this is the first case of promyelocytic transformation of Philadelphia chromosome negative untreated ET, in whom both t(15;17) and PML-RAR, fusion were proven. Am. J. Hematol. 71:114,116, 2002. © 2002 Wiley-Liss, Inc. [source] Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study,,CANCER, Issue 16 201070 milligrams twice daily, Efficacy, tolerability of 140 milligrams once daily Abstract BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML. Cancer 2010. © 2010 American Cancer Society. [source] Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion,CANCER, Issue 2 2010Kimmo Porkka MD Abstract BACKGROUND: Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS: To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS: With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS: Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy. Cancer 2010. © 2010 American Cancer Society. [source] Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009CANCER, Issue 23 2009Alfonso Quintás-Cardama MD Abstract Homoharringtonine (HHT) is a natural alkaloid that is obtained from various Cephalotaxus species. The mechanism of action by which HHT exerts its antitumor activity is through inhibition of protein synthesis and promotion of apoptosis. In the 1990s, HHT proved to be significantly active as salvage therapy for patients with chronic myeloid leukemia (CML) after failure on interferon,, therapy. However, the remarkable success of imatinib mesylate in the treatment of CML relegated HHT to oblivion. The development of omacetaxine mepesuccinate, a subcutaneously bioavailable semisynthetic form of HHT, and its activity in imatinib-resistant CML has established this agent for the second time as a valuable option in the management of this disease. Preliminary results appear to support the use of this agent for patients who have imatinib-resistant CML, including those who carry the tyrosine kinase inhibitor-insensitive mutation that exchanges the amino acids threonine and isoleucine at position 315 (the T315I mutation). In this article, the authors discuss the current data on omacetaxine and the prospects of this agent to be integrated into the state-of-the-art treatment algorithms for CML. Cancer 2009. © 2009 American Cancer Society. [source] | |||||||||||||||||||||||||||||||