TY - JOUR. T1 - Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. AU - Issa, Ghayas C.. AU - Kantarjian, Hagop M.. AU - Yin, C. Cameron. AU - Qiao, Wei. AU - Ravandi, Farhad. AU - Thomas, Deborah. AU - Short, Nicholas J.. AU - Sasaki, Koji. AU - Garcia-Manero, Guillermo. AU - Kadia, Tapan M.. AU - Cortes, Jorge E.. AU - Daver, Naval. AU - Borthakur, Gautam. AU - Jain, Nitin. AU - Konopleva, Marina. AU - Khouri, Issa. AU - Kebriaei, Partow. AU - Champlin, Richard E.. AU - Pierce, Sherry. AU - OBrien, Susan M.. AU - Jabbour, Elias. PY - 2017/2/1. Y1 - 2017/2/1. N2 - BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline ...
The aim of this study is to evaluate the long term survival outcomes in patients with Adult Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Philadelphia chromosome-negative ALL in the older adult (age ≥40 y): Standard multiagent chemotherapy regimen (eg, CALGB 8811 [daunorubicin, vincristine, prednisone, pegaspargase, cyclophosp... more
Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Childrens Oncology Group Study Academic Article ...
At the 59th American Society of Hematology (ASH) Annual Meeting & Exposition, Hunger et al presented data from the phase II CA180-372 study in pediatric patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) treated with dasatinib (Sprycel) added to a chemotherapy regimen modeled on a Berlin-Frankfurt-Munster high-risk backbone (Abstract 98). The combination demonstrated an event-free survival rate (the studys primary endpoint) of 65.5% (95% confidence interval [CI] = 57.7-73.7) and an overall survival rate of 91.5% (95% CI = 84.2-95.5) at 3 years. Dasatinib and chemotherapy were generally well tolerated in pediatric Philadelphia chromosome-positive ALL patients.. "Philadelphia chromosome-positive acute lymphoblastic leukemia remains a high-risk leukemia type," said lead study author Stephen Hunger, MD, Chief of the Division of Oncology and Director of the Center for Childhood Cancer Research at Childrens Hospital of Philadelphia. "In this study, the ...
Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients ,40 years 70 (50-90) % and for patients ,= 40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients ,40 years 10 (2-28) % compared to 25 (11-42) % for patients ,= 40 years (p = 0.04). ...
TY - JOUR. T1 - Philadelphia chromosome‐negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long term follow‐up results. AU - Cortes, Jorge E.. AU - Talpaz, Moshe. AU - Beran, Miloslav. AU - OBrien, Susan M.. AU - Rios, Mary B.. AU - Stass, Sanford. AU - Kantarjian, Hagop M.. PY - 1995/1/15. Y1 - 1995/1/15. N2 - Background. Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one‐third of them have rearrangements of the breakpoint cluster region (BCR‐positive). Methods. The authors analyzed the characteristics, treatment response, and prognosis of 23 patients with BCR‐positive, Ph‐negative CML, and compared them with patients with Ph‐positive CML, Ph‐negative BCR‐negative CML and chronic myelomonocytic leukemia (CMML) treated during the same period. Results. Seventeen patients had early chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had blastic ...
Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous ...
Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18-39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8-93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk
SILVER SPRING, Md. - The Food and Drug Administration has approved a new drug for treating a rare type of leukemia, the agency said Thursday.. The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.
The discovery of the Philadelphia chromosome as a hallmark of chronic myelogenous leukemia in 1960 by Peter Nowell provided evidence for a genetic link to cancer. As with most seminal scientific observations, the description of the Philadelphia chromosome posed many more questions than were answered. This Review series includes contributions from individuals who performed critical experiments addressing some of the most important of these questions, reflecting the nearly 50 years of work inspired by Nowells initial finding. The legacy of the Philadelphia chromosome now serves as a paradigm for how basic science discoveries can lead to effective new approaches for the treatment of human disease.
Vincristine Liposome is an anti-cancer chemotherapy drug used in the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia.
Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients / Alti kronik miyeloid losemi olgusunda farkli kirik noktali varyant Philadelphia translokasyonlari.
PURPOSE Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. PATIENTS AND METHODS We evaluated whether imatinib (340 mg/m(2)/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. RESULTS Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% +/- 11% (95% CI, 64% to 90%), more than twice historical controls
The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtaposing the ABL1 gene on chromosome 9 (region q34) to a part of the BCR (breakpoint cluster region) gene on chromosome 22 (region q11). This is a reciprocal translocation, creating an elongated chromosome 9 (termed a derivative chromosome, or der 9), and a truncated chromosome 22 (the Philadelphia chromosome, 22q-).[3][4] In agreement with the International System for Human Cytogenetic Nomenclature (ISCN), this chromosomal translocation is designated as t(9;22)(q34;q11). The symbol ABL is derived from Abelson, the name of a leukemia virus which carries a similar protein.. Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. This gene encodes for a Bcr-abl fusion protein. Depending on the precise location of fusion, the molecular weight of this protein ...
PRIMARY OBJECTIVES:. I. Determine the toxicities and estimate the maximum tolerated dose or the recommended phase 2 dose of dasatinib in pediatric patients with refractory solid tumors.. II. Determine the toxicities of dasatinib in pediatric patients with imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia.. III. Characterize the pharmacokinetics of dasatinib in pediatric patients with refractory solid tumors or imatinib-resistant Ph+ leukemia.. SECONDARY OBJECTIVES:. I. Preliminarily define the antitumor activity of dasatinib in pediatric patients with refractory solid tumors within the confines of a phase I study.. II. Obtain pilot data on the activity of dasatinib administered in pediatric patients with Ph+ leukemia.. III. Assess the biologic activity of dasatinib on tumor cells when available. IV. Determine the phosphotyrosine state of SRC and ABL substrates and correlate this with dasatinib dosage and antitumor activity (pharmacodynamics study).. OUTLINE: This is a ...
Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic ...
This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute L
OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11).CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented ...
For the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive or where there is prior TKI resistance or intolerance ...
Shares of Ariad Pharmaceuticals Inc. (ARIA) are up more than 5% in pre-market trading after the company this morning announced that Health Canada has approved the use of Iclusig in Canada for the treatment of adult patients with all phases of chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive, or where there is prior TKI resistance or intolerance.. "Patients with CML or Ph+ ALL can become resistant to their therapies over time," said in a statement Professor Jeffrey Lipton, Ph.D., M.D., staff physician at The Princess Margaret Cancer Centre and one of the PACE trial investigators. "Iclusig will be a valuable new therapeutic option in Canada for patients with refractory CML and Ph+ ALL, where we have a proven unmet medical need.". Last month, Ariad received approval of Iclusig (Ponatinib) in Israel.. ARIA shares ...
ARIAD Pharmaceuticals, Inc. (ARIAD) is an oncology company. The Company is focused on transforming the lives of cancer patients with medicines. The Companys product pipeline includes Iclusig (ponatinib), brigatinib, AP32788 and ridaforolimus. The Companys Iclusig is a tyrosine kinase inhibitor (TKI) that is approved in the United States, the European Union, Australia, Switzerland, Israel and Canada for the treatment of adult patients with chronic myeloid leukemia (CML), and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Its Brigatinib is an investigational inhibitor of anaplastic lymphoma kinase (ALK). Its AP32788 is a TKI, which is designed as a targeted therapy for patients with non-small cell lung cancer (NSCLC) with specific mutations in two kinases, epidermal growth factor receptor (EGFR), or human epidermal growth factor receptor 2 (HER2). Its Ridaforolimus is an investigational inhibitor of the mammalian target of rapamycin (mTOR).. ...
Gleevec has marked antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), but secondary resistance develops rapidly, reflecting the limitations of single-agent therapy. Experimental data suggest that interferon- (IFN-alpha) enhances the antileukemic activity of Gleevec. We therefore examined combined Gleevec and low-dose IFN-alpha in six patients with Ph+ALL who were ineligible for stem cell transplantation. All patients had received Gleevec for 0.5-4.8 months prior to IFN-alpha, for relapsed (n=3) or refractory (n=1) Ph+ALL or as an alternative to chemotherapy following severe treatment-related toxicity (n=2). Five patients were in hematologic remission (CR) with minimal residual disease (MRD+), one patient was refractory to Gleevec. Four of the five MRD+ patients are alive in CR after a median treatment duration of 20 (11-21) months. Two of these patients are in continuous CR 21 months after Gleevec was initiated, while the other two patients ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel® (dasatinib) tablets to include the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic
New Tyrosine Kinase Inhibitors. Gleevec is a tyrosine kinase inhibitor that was designed specifically for the treatment of leukemia associated with the Philadelphia chromosome abnormality. This drug has revolutionized the treatment of Philadelphia chromosome positive ALL. However, drug resistance occurs and patients with ALL can fail treatment. Therefore, there is considerable research into the development of new tyrosine kinase inhibitors that can overcome resistance to Gleevec. There are two drugs currently approved by the US Food and Drug Administration (FDA) for treating adult ALL patients that have failed Gleevec: Sprycel® (dasatinib) and Tasigna® (nilotinib). There are other tyrosine kinase inhibitors in the drug development pipeline that have not yet been approved by the FDA, including bosutinib (SK1606).. Sprycel® (dasatinib): Sprycel is a newly developed tyrosine kinase inhibitor that is more than 300 times more active than Gleevec for inhibition of Bcr-Abl (the abnormal protein ...
Study hypothesis: Treatment with dasatinib 100 mg QD is safe and efficacious when given to patients with Ph+ ALL in the post SCT setting.
Roy A, Bradburn M, Moorman AV, Burrett J, Mitchell C, Kinsey SE, Vora AJ, Lilleyman J, Eden O, Hann I & Saha V (2004) Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: Results of the Medical Research Council ALL 97 trial ...
Daily life flies into brick wall. You go along, you dont feel well, you finally decide to get some tests and at the end of the tests you get the Diagnosis: Philadelphia chromosome positive, Acute Lymphoblastic Leukemia (ALL), B-cell. Not knowing what to think, you take a day to prepare, not knowing for what or…
Researchers from Huntsman Cancer Institute (HCI) at the University of Utah have developed a new drug that can potentially be used as a standalone or combination treatment against a common blood cancer.. The new drug, described in a paper published in the journal Leukemia, is capable of inhibiting and overriding the negative activity of the so-called Philadelphia chromosome, which is present in up to 30 percent of adults diagnosed with acute lymphoblastic leukemia (ALL).. "When you treat these leukemia cells with chemotherapy, you want DNA damage to accumulate so the cancer cells will die. But because the Philadelphia chromosome continually causes repair, these cells dont retain enough DNA damage to die," said Srividya Bhaskara, Ph.D., an assistant professor of radiation oncology at the University of Utah and lead author of the study, in a press release. "Essentially they resist any kind of drug you use on them. So we had to find a new way to overcome this DNA repair addiction.". For the new ...
This line was was derived from malignant cells collected from the bone marrow of an 8 year old child with Philadelphia chromosome positive B cell ALL.
This line was was derived from malignant cells collected from the bone marrow of an 8 year old child with Philadelphia chromosome positive B cell ALL.
In this episode of The Drexel InterView, host Paula Marantz Cohen interviews Jessica Wapner, author of The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level. This book discusses the painstaking research process leading to the development of the "miracle" drug, Gleevec. Gleevec effectively eradicates symptoms of chronic myeloid leukemia (CML), a cancer of the white blood cells. The story of Gleevec is an adventure story, a mystery, an intellectual journey, and a triumphant narrative-one which Wapner tells with extraordinary eloquence and lucidity. She traces the process that began with the discovery of the Philadelphia chromosome, a genetic mutation associated with CML. Wapner then explains the science behind "rational drug design" of the sort used for Gleevec to treat cancer without chemotherapy. She also discusses the politics of drug development, and gives a balanced assessment of the sometimes-conflicting interests of researchers, corporate executives, ...
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I have read that Gleevec is used to treat a particular type of leukaemia, caused by the Philadelphia Chromosome. My leukaemia is not of that type, but...
We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative ...
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APA Citation Wapner, Jessica. () The Philadelphia chromosome :a genetic mystery, a lethal cancer, and the improbable invention of a lifesaving treatment MLA Citation Wapner, Jessica. The Philadelphia Chromosome: A Genetic Mystery, A Lethal Cancer, And The Improbable Invention Of A Lifesaving Treatment. : . Print.. These citations may not conform precisely to your selected citation style. Please use this display as a guideline and modify as needed.. ...
Cancer statistics, 2009. CA Cancer J Clin (2009) 83.57 Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med (2014) 8.21 High drug attrition rates--where are we going wrong? Nat Rev Clin Oncol (2011) 5.67 Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med (2014) 5.37 The pediatric preclinical testing program: description of models and early testing results. Pediatr Blood Cancer (2007) 5.28 Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a childrens oncology group study. J Clin Oncol (2009) 4.20 Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol (2010) 4.09 IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer (2010) 4.08 Targeting apoptosis pathways in cancer ...
malignancies of blast cells with few identifying characteristics. When cytochemical stains became available, it was possible to divide these objectively into myeloid malignancies and acute leukemias of lymphoid cells. Acute leukemias of lymphoid cells have been subdivided based on morphologic characteristics by the French-American-British (FAB) group (Table 110-2). Using this system, lymphoid malignancies of small uniform blasts (e.g., typical childhood acute lymphoblastic leukemia) were called L1, lymphoid malignancies with larger and more variable size cells were called L2, and lymphoid malignancies of uniform cells with basophilic and sometimes vacuolated cytoplasm were called L3 (e.g., typical Burkitts lymphoma cells). Acute leukemias of lymphoid cells have also been subdivided based on immunologic (i.e., T cell vs. B cell) and cytogenetic abnormalities (Table 110-2). Major cytogenetic subgroups include the t(9;22) (e.g., Philadelphia chromosome-positive acute lymphoblastic leukemia) and ...
Huan, Chen,Liu, Kai-Yan,Xu Lan-ping,et al. Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[J]. BLOOD,2014,124(21 ...
Background Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. Methods In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed. Results A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced
Introduction: The BCR-ABL1 tyrosine kinase induces malignant transformation of B cells at the pre-B cell checkpoint and induces Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). In a genome-wide search, we identified FOXM1 as a transcription factor that is specifically upregulated at the pre-B cell checkpoint. FOXM1 is a forkhead box transcription factor and a key regulator of cell growth by promoting cell cycle progression. Results: We transformed murine pre-B cells with a retroviral BCR-ABL1 expression vector and observed upregulation of Foxm1 protein levels. Consistent with this, FOXM1 protein levels in patient-derived Ph+ ALL samples are ∼10-fold higher than in healthy B cells and B cell precursors (n=5; P=0.01). In a cohort of 83 Ph+ ALL patients, the FOXM1 promoter region was significantly de-methylated compared to normal pre-B cells (n=12; P=2.4x10e-7). In order to evaluate a potential predictive value of FOXM1 expression in ALL cells, we correlated FOXM1 mRNA ...
The US Food and Drug Administration (FDA) has approved Bosulif (bosutinib) to treat adults with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).Indications: Bosulif is a kinase inhibitor indicated for the treatment of adult patients with newly-diagnosed chronic phase Ph+ CML.Dosage and administration: 400 mg orally once daily with food.
Patients With Relapsed or Refractory ALL - INO-VATE ALL. The safety and efficacy of BESPONSA were evaluated in INO-VATE ALL (NCT01564784) a randomized (1:1), open-label, international, multicenter study in patients with relapsed or refractory ALL. Patients were stratified at randomization based on duration of first remission (, 12 months or ≥ 12 months, salvage treatment (Salvage 1 or 2) and patient age at randomization (, 55 or ≥ 55 years). Eligible patients were ≥ 18 years of age with Philadelphia chromosome-negative or Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL. All patients were required to have ≥ 5% bone marrow blasts and to have received 1 or 2 previous induction chemotherapy regimens for ALL. Patients with Philadelphia chromosome-positive B-cell precursor ALL were required to have disease that failed treatment with at least 1 tyrosine kinase inhibitor and standard chemotherapy. Table 1 shows the dosing regimen used to treat patients.. Among all ...
Clinicians who perform radiation therapy (RT) are exposed to radiation, which may negatively affect their health. The present study reports a case of acute lymphoblastic leukemia in a healthcare provider who was exposed to radiation at work; we also present a literature review of this topic. A 45-year-old patient, who had been a radiation oncologist and had been exposed to radiation while performing brachytherapy 10 years ago, complained of chest pain and was suspected of having leukemia based on the results of a blood test in an outpatient clinic. He was diagnosed with acute lymphoblastic leukemia, and subsequently underwent chemotherapy. However, the case died during treatment. Through epidemiological investigation, it was found that the cases cumulative exposure dose based on personal exposure and spatial dose measured during the work period was in the range of 6.08-12.15 mSv. Based on the following considerations, acute lymphoblastic leukemia was highly correlated with the level of radiation to
A fusion gene is a hybrid gene formed from two previously separate genes. It can occur as a result of: translocation, interstitial deletion, or chromosomal inversion. The first fusion gene was described in cancer cells in the early 1980s. The finding was based on the discovery in 1960 by Peter Nowell and David Hungerford in Philadelphia of a small abnormal marker chromosome in patients with chronic myeloid leukemia-the first consistent chromosome abnormality detected in a human malignancy, later designated the Philadelphia chromosome. In 1973, Janet Rowley in Chicago showed that the Philadelphia chromosome had originated through a translocation between chromosomes 9 and 22, and not through a simple deletion of chromosome 22 as was previously thought. Several investigators in the early 1980s showed that the Philadelphia chromosome translocation led to the formation of a new BCR/ABL1 fusion gene, composed of the 3 part of the ABL1 gene in the breakpoint on chromosome 9 and the 5 part of a gene ...