New life-saving treatments for Acute Lymphoblastic Leukemia in clinical trial on AALL1631: International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Ph+ ALL Testing Imatinib in Combination with Two Different Cytotoxic Chemotherapy Backbones

TY - JOUR. T1 - Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. T2 - Childrens oncology group study AALL0031. AU - Schultz, K. R.. AU - Carroll, A.. AU - Heerema, N. A.. AU - Bowman, W. P.. AU - Aledo, A.. AU - Slayton, W. B.. AU - Sather, H.. AU - Devidas, M.. AU - Zheng, H. W.. AU - Davies, S. M.. AU - Gaynon, P. S.. AU - Trigg, M.. AU - Rutledge, R.. AU - Jorstad, D.. AU - Winick, N.. AU - Borowitz, M. J.. AU - Hunger, S. P.. AU - Carroll, W. L.. AU - Camitta, B.. N1 - Funding Information: We sincerely thank Laura Francisco for invaluable data management support, Tammie Eslinger, CCRP, for outstanding protocol development and performance support and Bernice Pasut, RN, for diligent and thorough protocol development support. SPH is the Ergen Family Chair in Pediatric Cancer. This work was supported by grants CA98543 and CA29139.. PY - 2014/7. Y1 - 2014/7. N2 - We previously reported preliminary findings that post induction imatinib ...

Improved early event-free survival with imatinib in Philadelphia chromosome - Positive acute lymphoblastic leukemia: A Childrens Oncology Group Study Academic Article ...

The aim of this study is to evaluate the long term survival outcomes in patients with Adult Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

TY - JOUR. T1 - Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia. T2 - A review. AU - Bachanova, V.. AU - Weisdorf, D.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2008/3. Y1 - 2008/3. N2 - Acute lymphoblastic leukemia is highly sensitive to induction chemotherapy; however, long-term survival in adults has been less than 35%, primarily as a result of high relapse rate. Treatment for relapsed disease is even less successful. The optimal post-remission therapy in the first complete remission offers the best opportunity for leukemia-free survival. Allogeneic donor stem cell transplantation can offer a unique anti-leukemia effect and a potential for extended survival. We will discuss advances in unrelated donor (URD) stem cells transplantation, improvements in transplantation process and supportive care along with growing experience with umbilical cord blood (UCB) allografts.. AB - Acute lymphoblastic leukemia is highly sensitive to ...

Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the ...

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TY - JOUR. T1 - Six candidate miRNAs associated with early relapse in pediatric b-cell acute lymphoblastic leukemia. AU - Amankwah, Ernest K.. AU - Devidas, Meenakshi. AU - Teachey, David T.. AU - Rabin, Karen R.. AU - Brown, Patrick A.. PY - 2020/6. Y1 - 2020/6. N2 - Background/Aim: Few studies have evaluated the role of miRNAs in pediatric acute lymphoblastic leukemia (ALL) relapse and a consensus of a clinically significant miRNA signature is yet to be identified. In this study, we evaluated miRNAs associated with pediatric B-ALL early relapse in two independent sample sets. Materials and Methods: We performed global miRNA profiling on diagnostic bone marrow specimens from six early relapse (?3 years after diagnosis) and six age- and cytogenetics-matched prolonged remission (?4 years) patients (first set) and an independent set of 14 early relapse and 14 matched prolonged remission specimens (second set). Results: Twelve and 39 top differentially expressed miRNAs were observed in the first ...

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). ...

Single-agent use of blinatumomab resulted in anti-leukemic activity in patients with tyrosine kinase inhibitor-relapsed or refractory Philadelphia chromosome positive B-precursor acute lymphoblastic leukemia.

The U.S. Food and Drug Administration today approved Besponsa (inotuzumab ozogamicin) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).. For adult patients with B-cell ALL whose cancer has not responded to initial treatment or has returned after treatment, life expectancy is typically low, said Richard Pazdur, M.D., director of the FDAs Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDAs Center for Drug Evaluation and Research. These patients have few treatments available and todays approval provides a new, targeted treatment option.. B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell. The National Cancer Institute estimates that approximately 5,970 people in the United States will be diagnosed with ALL this year and approximately 1,440 will die from the ...

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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 ...

Dana-Farber employs more than 4,274 full-time and part-time people, 467 faculty, and has annual gross revenues of about $1,086,638,000.[1] There are more than 299,202 adult and pediatric patient visits a year, and it is involved in more than 700 clinical trials. It is internationally known for its research and clinical excellence. Expertscape ranks its programs in aplastic anemia[2] and multiple myeloma[3] as best in the world. It has been also ranked the fourth best cancer hospital in the United States by U.S. News & World Report.[4] Dana-Farber is a member of the Multiple Myeloma Research Consortium. In addition to being a principal teaching affiliate of Harvard Medical School, Dana-Farber is also a federally designated Center for AIDS Research, and a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC),[5] a federally designated Comprehensive Cancer Center. Providing advanced training in cancer treatment and research for an international faculty, Dana-Farber conducts ...

TY - JOUR. T1 - Clinical Utility of Initial Terminal Deoxynucleotidyl Transferase Determinations in Childhood Acute Leukemias. AU - Kalwinsky, David K.. AU - Weatherred, William H.. AU - Dahl, Gary V.. AU - Bowman, W. Paul. AU - Melvin, Susan L.. AU - Coleman, Mary Sue. AU - Bollum, F. J.. PY - 1981/7/1. Y1 - 1981/7/1. N2 - Terminal deoxynucleotidyl transferase (TDT) activity was measured in bone marrow lymphoblasts obtained at diagnosis from 168 consecutive patients with childhood acute leukemia. Absolute concentrations of TDT were increased (,20 units/108 blasts) in samples from 98 of 112 assessable patients with acute lymphocytic leukemia (ALL). The values ranged from ,1 to 1502 units/108 blasts with a median of 90 units contrasted with ,1 to 219 units (median, 2.6 units) in studies of children without leukemia. Results of an immunofluorescence assay were in good agreement with enzymatic detection of the polymerase. Among 115 patients with adequate marrow smears, 105 had TDT-positive blasts. ...

Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups ...

In vitro and in vivo resistance to prednisolone are predictive for an adverse prognosis in pediatric precursor-B acute lymphoblastic leukemia. Causes of resistance are still poorly understood. In this study, we observed that prednisolone exposure of prednisolone-sensitive patients leukemic cells decreased anti-apoptotic MCL1 protein levels by 2.9-fold, while MCL1 protein expression in prednisolone-resistant leukemic patients cells was unaffected (p,0.01). Locked nucleic acid oligonucleotides directed against MCL1 (MCL1 LNA) reduced MCL1 protein levels by 82 +/- 16% (p,0.05) in leukemic cells, decreased proliferation by 9-fold and sensitized to prednisolone up to 80.8-fold, compared to a non-silencing-control LNA (p,0.05). Remarkably, we discovered that MCL1-silencing upregulated the glucose consumption of leukemic cells by 2.5-fold (p,0.05), suggesting a potential rescue mechanism mediated by glycolysis. Targeting glycolysis by 2-deoxyglucose (2-DG) synergistically inhibited leukemic survival ...

BOSTONThe Dana-Farber Cancer Institute and the National Foundation for...With eight other NFCR research centers at universities and research ho...How the Center Works...Traditionally monoclonal antibodies have been derived from mouse mode...,Dana-Farber,launches,NFCR,Center,for,Therapeutic,Antibody,Research,and,Engineering,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters

BACKGROUND: Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens. METHODS: This open-label randomised trial was undertaken in 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1-18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk, intermediate-risk, and standard-risk groups on the basis of duration of first complete remission, site of relapse, and immunophenotype. All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. Neither patients nor those giving interventions were masked. After three blocks of therapy, all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease (≥10(-4)

BACKGROUND: Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens. METHODS: This open-label randomised trial was undertaken in 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1-18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk, intermediate-risk, and standard-risk groups on the basis of duration of first complete remission, site of relapse, and immunophenotype. All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. Neither patients nor those giving interventions were masked. After three blocks of therapy, all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease (≥10(-4)

2017 PCF Challenge Award ($1 Million) Principal Investigators: Howard Scher, MD (Memorial Sloan Kettering Cancer Center), Mary-Ellen Taplin, MD (Harvard: Dana-Farber Cancer Institute) Co-Investigators: Wassim Abida, MD, PhD (Memorial Sloan Kettering Cancer Center), Anuradha Gopalan, MD (Memorial Sloan Kettering Cancer Center), Glenn Heller, PhD (Memorial Sloan Kettering Cancer Center), Maika Mitchell, PhD (Memorial Sloan Kettering Cancer Center), Nikolaus Schultz, PhD (Memorial Sloan Kettering Cancer Center), Steven Balk, MD, PhD (Harvard: Beth Israel Deaconess Medical Center), Atish Choudhury, MD, PhD (Harvard: Dana-Farber Cancer Institute), Eliezer Van Allen, MD (Harvard: Dana-Farber Cancer Institute), Adam Kibel, MD (Harvard: Brigham and Womens Hospital), Huihui Ye, MD, MSc (Harvard: Beth Israel Deaconess Medical Center), Rosina Lis, MD (Harvard: Dana-Farber Cancer Institute), Wai Yi Tsui, MD, PhD (Memorial Sloan Kettering Cancer Center), Michaela Bowden, PhD (Harvard: Dana-Farber Cancer ...

Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has provided valuable prognostic markers for treatment stratification. However, reports of cytogenetic studies of relapsed ALL samples are limited. We compared the karyotypes from 436 nonselected B-cell precursor ALL patients at initial diagnosis and of 76 patients at first relapse. We noticed a relative increase of karyotypes that did not fall into the classic ALL cytogenetic subgroups (high hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), ,45 chromosomes) in a group of 29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non-classical cytogenetic aberrations in these 29 patients were mostly found on chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal translocations, three of which involved 14q32. The most frequent abnormalities were found in 9p (12/29 cases) and were associated with a marked decrease in the duration of the second remission, but not of the probability of ...

TY - JOUR. T1 - Hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and Down syndrome. AU - Goto, Hiroaki. AU - Kaneko, Takashi. AU - Shioda, Yoko. AU - Kajiwara, Michiko. AU - Sakashita, Kazuo. AU - Kitoh, Toshiyuki. AU - Hayakawa, Akira. AU - Miki, Mizuka. AU - Kato, Keisuke. AU - Ogawa, Atsushi. AU - Hashii, Yoshiko. AU - Inukai, Takeshi. AU - Kato, Chiaki. AU - Sakamaki, Hisashi. AU - Yabe, Hiromasa. AU - Suzuki, Ritsuro. AU - Kato, Koji. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Background: Hematopoietic stem cell transplantation (HSCT) is one curable option for high-risk acute lymphoblastic leukemia (ALL); however, transplant-related toxicities might be severe in patients with Down syndrome and ALL (DS-ALL). Procedure: HSCTs performed in patients with DS-ALL were identified in the Japan Society for Hematopoietic Cell Transplantation registry. Results: In the registry data, 11 patients with DS-ALL were identified. The median age at HSCT was 9 years (range: 6-22 ...

Method A population-based case-control study of childhood ALL was conducted in Australia. Information about the occupational pesticide exposure of mothers and fathers was collected using job-specific modules. Information on the types and extent of pesticide exposure was collected for mothers and fathers before and around the time of conception, and also for mothers during pregnancy for the index case or control and for 1 year after birth.. ...

The strategy for treating relapsed and refractory adult ALL patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation, provided that the toxicity of the salvage regimen is acceptable. However, this leukemia is characterized as being highly refractory to standard chemotherapy and therefore novel therapeutic approaches are desperately needed. Clofarabine is a second generation nucleoside analog FDA approved for the treatment of relapsed and refractory pediatric ALL. Clofarabine has been administered to adult patients with hematologic malignancies with an acceptable toxicity profile with 8% of relapsed ALL patients attaining a complete response (CR). The maximum tolerated dose (MTD) of clofarabine IV in adult patients has been determined to be 40 mg/m2/day for 5 consecutive days, which is lower than the tolerable daily dose for pediatric patients, 52 mg/m2/day. More recently, Karp and colleagues reported their experience with clofarabine in combination with ...

Järviaho T, Bang B, Zachariadis V, Taylan F, Moilanen J, Möttönen M, Smith CIE, Harila-Saari A, Niinimäki R, Nordgren A Blood Adv 3 (18) 2722-2731 [2019-09-24; online 2019-09-15] Pathogenic germline variants in ETV6 have been associated with familial predisposition to thrombocytopenia and hematological malignancies, predominantly childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In addition, overrepresentation of a high hyperdiploid subtype and older age at diagnosis have been reported among sporadic BCP-ALL cases with germline variants in ETV6 We studied a family with 2 second-degree relatives who developed childhood high hyperdiploid BCP-ALL at ages 8 and 12 years, respectively. A constitutional balanced reciprocal translocation t(12;14)(p13.2;q23.1) was discovered in both patients by routine karyotyping at diagnosis and, subsequently, in 7 healthy family members who had not experienced hematological malignancies. No carriers had thrombocytopenia. Whole-genome sequencing ...

A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Childhood acute lymphoblastic leukemia

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A variety of efforts are underway to apply gene therapy to cancer treatment. Most are in early, exploratory stages, where theyre being studied in the laboratory or in clinical research trials. One approach, however, known as CAR T-cell therapy, has received approval from the U.S. Food and Drug Administration for use as a therapy in certain groups of patients and is expected to receive additional approvals in the near future.. Research in gene therapy for cancer is currently focused in multiple areas, including genetically engineered viruses that directly kill cancer cells, gene transfer to alter the abnormal functioning of cancer cells, and immunotherapy (which includes CAR T-cell therapy), which helps the immune system better find and kill tumor cells.. Learn more about immunotherapy from the Center for Immuno-Oncology at Dana-Farber Cancer Institute.. Genetically Engineered Viruses. This approach uses specially modified viruses (called oncolytic viruses) that target and destroy cancer cells ...

2017 PCF Challenge Award ($1 Million) Award Donor: Janssen Pharmaceuticals Principal Investigators: Howard Scher, MD (Memorial Sloan Kettering Cancer Center), Mary-Ellen Taplin, MD (Harvard: Dana-Farber Cancer Institute) Co-Investigators: Wassim Abida, MD, PhD (Memorial Sloan Kettering Cancer Center), Anuradha Gopalan, MD (Memorial Sloan Kettering Cancer Center), Glenn Heller, PhD (Memorial Sloan Kettering Cancer Center), Maika Mitchell, PhD (Memorial Sloan Kettering Cancer Center), Nikolaus Schultz, PhD (Memorial Sloan Kettering Cancer Center), Steven Balk, MD, PhD (Harvard: Beth Israel Deaconess Medical Center), Atish Choudhury, MD, PhD (Harvard: Dana-Farber Cancer Institute), Eliezer Van Allen, MD (Harvard: Dana-Farber Cancer Institute), Adam Kibel, MD (Harvard: Brigham and Womens Hospital), Huihui Ye, MD, MSc (Harvard: Beth Israel Deaconess Medical Center), Rosina Lis, MD (Harvard: Dana-Farber Cancer Institute), Wai Yi Tsui, MD, PhD (Memorial Sloan Kettering Cancer Center), Michaela Bowden, ...

Results: A positive correlation was demonstrated between cfDNA and age (p=0.018; r=0.177). Pre-transplant cfDNA levels were found to be lower in bcr-abl (+) patients (p=0.001), whilst an adverse correlation was indicated between cfDNA and bcr-abl levels (p=0.001; r=-0.531). Akut lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented signficantly lower pre-transplant cfDNA levels. Cell free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cfDNA levels (p=0.024). Overall survival was not statistically different between high- and low-cfDNA groups (45.2% vs 22.5; p=0.821 ...

Results: A positive correlation was demonstrated between cfDNA and age (p=0.018; r=0.177). Pre-transplant cfDNA levels were found to be lower in bcr-abl (+) patients (p=0.001), whilst an adverse correlation was indicated between cfDNA and bcr-abl levels (p=0.001; r=-0.531). Akut lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented signficantly lower pre-transplant cfDNA levels. Cell free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cfDNA levels (p=0.024). Overall survival was not statistically different between high- and low-cfDNA groups (45.2% vs 22.5; p=0.821 ...

TY - JOUR. T1 - Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors. AU - Jones, Dan. AU - Thomas, Deborah. AU - Yin, C. Cameron. AU - OBrien, Susan. AU - Cortes, Jorge E.. AU - Jabbour, Elias. AU - Breeden, Megan. AU - Giles, Francis J.. AU - Zhao, Weiqiang. AU - Kantarjian, Hagop M.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2008/9/1. Y1 - 2008/9/1. N2 - BACKGROUND. BCR-ABL kinase domain (KD) mutations are detected in approximately 45% of patients with imatinib-resistant chronic myeloid leukemia. Patterns of KD mutations in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) are less well studied. METHODS. The authors assessed KD mutations in patients with recurrent Phpositive ALL after treatments that included 1 or more kinase inhibitors (n = 24 patients) or no prior kinase inhibitor (KI) therapy (n = 12 patients). RESULTS. ABL KD mutations were ...

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Monoclonal antibodies, such as blinatumomab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia ...

Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous ...

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 ...

Health,Dana-Farber Cancer Institute scientists have developed a test that is ...The researchers demonstrated that chronic lymphocytic leukemia CL...The research in the laboratory of Anthony Letai MD PhD of Dana-...Letai was a colleague of the late Stanley J. Korsmeyer MD of Dan...Inspired by this pioneering research drug companies have begun te...,New,Test,Predicts,CLLs,Sensitivity,to,Experimental,Drug,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news

Dana-Farber Cancer Institute is a top cancer center where leading mesothelioma doctors use the latest mesothelioma treatment protocols to help their cancer patients.

TY - JOUR. T1 - Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia. AU - Lovisa, Federica. AU - Zecca, Marco. AU - Rossi, Bartolomeo. AU - Campeggio, Mimma. AU - Magrin, Elisa. AU - Giarin, Emanuela. AU - Buldini, Barbara. AU - Songia, Simona. AU - Cazzaniga, Giovanni. AU - Mina, Tommaso. AU - Acquafredda, Gloria. AU - Quarello, Paola. AU - Locatelli, Franco. AU - Fagioli, Franca. AU - Basso, Giuseppe. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT ...

TY - JOUR. T1 - Direct Reversal of Glucocorticoid Resistance by AKT Inhibition in Acute Lymphoblastic Leukemia. AU - Piovan, Erich. AU - Yu, Jiyang. AU - Tosello, Valeria. AU - Herranz, Daniel. AU - Ambesi-Impiombato, Alberto. AU - DaSilva, Ana Carolina. AU - Sanchez-Martin, Marta. AU - Perez-Garcia, Arianne. AU - Rigo, Isaura. AU - Castillo, Mireia. AU - Indraccolo, Stefano. AU - Cross, Justin R.. AU - deStanchina, Elisa. AU - Paietta, Elisabeth. AU - Racevskis, Janis. AU - Rowe, Jacob M.. AU - Tallman, Martin S.. AU - Basso, Giuseppe. AU - Meijerink, Jules P.. AU - Cordon-Cardo, Carlos. AU - Califano, Andrea. AU - Ferrando, Adolfo A.. PY - 2013/12/9. Y1 - 2013/12/9. N2 - Glucocorticoid resistance is a major driver of therapeutic failure in Tcell acute lymphoblastic leukemia (T-ALL). Here, we identify the AKT1 kinase as a major negative regulator of the NR3C1 glucocorticoid receptor protein activity driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 impairs glucocorticoid-induced ...

Background: Chromosomal translocations resulting in alternative fusions of the human TEL (ETV6) and JAK2 genes have been observed in cases of acute lymphoblastic leukemia and chronic myelogenous leukemia, but a full understanding of their role in disease etiology has remained elusive. This study investigated potential differences between these alternate TEL-JAK2 fusions, including their lineage specificity. Design and Methods: Both T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia derived TEL-JAK2 fusion types were generated using the corresponding zebrafish tel and jak2a genes and placed under the control of either the white blood cell-specific spi1 promoter or the ubiquitously-expressed cytomegalovirus promoter. These constructs were injected into zebrafish embryos and their effects on hematopoiesis examined using a range of molecular approaches. In addition, the functional properties of the alternate fusions were investigated in vitro. Results: Injection of the ...

TY - JOUR. T1 - Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type. T2 - Long-term follow-up in acute promyelocytic leukemia. AU - Jurcic, Joseph G.. AU - Nimer, Stephen D.. AU - Scheinberg, David A.. AU - Deblasio, Tony. AU - Warrell, Raymond P.. AU - Miller, Wilson H.. N1 - Copyright: Copyright 2021 Elsevier B.V., All rights reserved.. PY - 2001/11/1. Y1 - 2001/11/1. N2 - The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-α fusion messenger RNA species that can be detected by reverse transcription-polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-α Isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, , 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. ...

Chromosomal abnormalities are diagnostic and prognostic key factors in acute myeloid leukemia (AML) patients, as they play a central role for risk stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic abnormality seen commonly in elder male AML patients, is normally categorized under AML with complex karyotype (CK). Accordingly, patients with HH generally are associated with low remission rates and a short overall survival. Here we report a case of 21-year-old female, diagnosed with a de novo AML-M1 according to WHO classification and a CK at diagnosis. Cytogenetic, molecular cytogenetic approaches (standard fluorescence in situ hybridization (FISH), array-proven multicolor banding (aMCB)) and high resolution array comparative genomic hybridization (aCGH) analyses revealed a unique complex but still near diploid karyotype involving eleven chromosomes was identified. It included pentasomy 4, three yet unreported chromosomal aberrations t(1;2)(p35;p22), t(1;3)(p36.2;p26.2), and t(10;12)

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

The goal of precision medicine cancer therapies is to use drugs that target the molecular aberrations that drive cancers to improve cure rates and decrease toxicity. The Childrens Oncology Group (COG) high risk acute lymphoblastic leukemia (HR ALL) TARGET Project is a large collaborative effort led by Stephen Hunger, MD, and involving the the National Cancer Institute Office of Cancer Genomics, and investigators from Childrens Hospital of Philadelphia, Nationwide Childrens Hospital, St. Jude Childrens Research Hospital, the University of Florida, the University of New Mexico and the University of California San Francisco.. The research team has used next generation sequencing technology to study high risk ALL, leading to a large number of observations that have revolutionized understanding of the genomic landscape of ALL and identified new therapeutic targets in ALL subsets with poor treatment outcome. Based on findings from these studies, the COG AALL1131 clinical trial for children, ...

Using a selection-based cDNA library screen, we identified the cytokine receptor subunit CRLF2 as a factor in poor-risk B-ALL. The screen, which uses tumor-derived mRNA to assay for transcripts that can substitute for IL3 signaling, is broadly applicable to other tumor types, as many gain-of-function alterations in epithelial and mesenchymal malignancies (e.g., mutant EGFR, KIT, ERBB2, ALK, and EWS) confer IL3 independence in BaF3 cells (29-34). The alterations identified by the screen are functionally relevant and therefore attractive therapeutic targets.. Our data suggests that routine screening of B-ALL for CRLF2 expression, either by IHC or flow cytometry, offers prognostic value. CRLF2 overexpression was associated with high-risk disease in children and a dismal prognosis in adults. Marked enrichment of the adult CRLF2 overexpression signature among pediatric B-ALL suggests that CRLF2 overexpression drives a similar disease in children and adults. Like FLT3 mutations in acute myelogenous ...

With new approaches to therapy and increased understanding of the biology of cancer, breast cancer treatment has made significant progress in recent years.. I am personally very excited about whats to come for breast cancer treatment, says Eric Winer, MD, director of the Breast Oncology Program in the Susan F. Smith Center for Womens Cancers at Dana-Farber. I think we will have drugs available in the clinic in the next several years that may have a dramatic impact on outcomes for women with breast cancer.. Winer discussed the latest in breast cancer treatment and research during a live video webchat hosted by Dana-Farber last month. The chat, which featured questions submitted by patients and caregivers, covered topics on tamoxifen, aromatase inhibitors, and new treatment options for HER2-postiive and triple-negative breast cancers.. View a video of the May 22 webchat below. For more information on breast cancer, visit the website for the Susan F. Smith Centers Breast Oncology ...

The patients in this study showed similar clinical features, as compared with previous reports on iAMP21. Patients with iAMP21 comprised 3.4% of pediatric BCP-ALL patients in this study, which was concordant with 2% in other studies. Other features of iAMP21 such as the presence of a low WBC count and older age at initial diagnosis were also observed. None of the patients were under three years of age. None of the patients showed a WBC count above 50×109/L. In this study, two of 10 cases (20%) showed replacement of a normal chromosome 21 with an abnormal marker chromosome. Four of 10 patients (40%) showed normal karyotype. iAMP21 patients with normal karyotype varied from 0% [1] to 43% [10] in other reports, which could be mainly due to the difference in specimen quality and detection sensitivity of each test.. Some findings in this study have not been clearly described in previous reports. There were significantly more SER in the iAMP21 patient group than in the no iAMP21 patient group. Most ...

Allogeneic bone marrow transplantation (stem cell transplant) in acute lymphoblastic leukemia (ALL) (costs for program #253329) ✔ Academic Hospital Neuperlach ✔ Department of Hematology and Oncology ✔ BookingHealth.com

Allogeneic bone marrow transplantation (stem cell transplant) in acute lymphoblastic leukemia (ALL) (costs for program #260823) ✔ University Hospital Münster ✔ Department of Hematology, Hemostaseology, Oncology and Pneumology (Medical Department A) ✔ BookingHealth.com

The common belief in childhood pB-ALL development is that children with intrinsic genetic susceptibility to pB-ALL development acquire additional chromosomal aberrations, i.e., ETV6-RUNX1-most of them in utero during fetal hematopoiesis-as a primary pathogenetic event followed by a broad range of secondary mutational events resulting in a full-blown leukemia. Common among these secondary events are alterations disrupting the PAX5 gene, which encodes a master transcriptional regulator of B-cell development (13, 14). In this setting, PAX5 seems to retain driver functions in established leukemia because restoring endogenous PAX5 expression triggers disease remission (23).. Recent discoveries of inherited mutations of PAX5 in a new syndrome of susceptibility to pB-ALL have extended the role of PAX5 alterations in the pathogenesis of pB-ALL (5, 6). The presence of the inherited mutations of PAX5 seems to produce a persistent and hidden preleukemic clone that may convert to pB-ALL in only a fraction ...

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 ...

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 ...

About 3,800 new cases of acute lymphocytic leukemia (ALL) are diagnosed each year in the United States. It is the most common type of leukemia under the age of 15. Children are most likely to develop the disease, but it can occur at any age. Acute lymphocytic leukemia may be called by several names, including acute lymphoid leukemia and acute lymphoblastic leukemia.. ALL results from an acquired (not inherited) genetic injury to the DNA of a single cell in the bone marrow. The disease is often referred to as acute lymphoblastic leukemia because the leukemic cell that replaces the normal marrow is the (leukemic) lymphoblast. The effects are: 1) the uncontrolled and exaggerated growth and accumulation of cells called lymphoblasts or leukemic blasts, which fail to function as normal blood cells and 2) the blockade of the production of normal marrow cells, leading to a deficiency of red cells (anemia), platelets (thrombocytopenia), and normal white cells (especially neutrophils, i.e., ...

abstractNote = {A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author ...

On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving 6MP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients ...

For long, T-cell acute lymphoblastic leukemia (T-ALL) remained in the shadow of precursor B-ALL because it was more seldom, and showed a normal karyotype in more than 50% of cases. The last decennia, intense research has been carried out on different fronts. On one side, development of normal thymocyte and its regulation mechanisms have been studied in multiple mouse models and subsequently validated. On the other side, molecular cytogenetics (fluorescence in situ hybridization) and mutation analysis revealed cytogenetically cryptic aberrations in almost all cases of T-ALL. Also, expression microarray analysis disclosed gene expression signatures that recapitulate specific stages of thymocyte development. Investigations are still very much actual, fed by the discovery of new genetic aberrations. In this review, we present a summary of the current cytogenetic changes associated with T-ALL. The genes deregulated by translocations or mutations appear to encode proteins that are also implicated in ...

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).. ...

Clinical trial for childhood ALL , Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft

Second thyroid neoplasms after prophylactic cranial irradiation for acute lymphoblastic leukemia | Perel, Yves; Leverger, Guy; Carrere, Anne; Caudry, Michel; Garabedian, Erea Noel; Ansoborlo, Sophie; Vergnes, Pierre | download | BookSC. Download books for free. Find books

Join us for St. Jude in the Big Easy, benefiting St. Jude Childrens Research Hospital. Guests will enjoy cocktails, dinner and stories shared by a local St. Jude patient. Guests will also have the opportunity to bid on live and silent auction items. All proceeds from this gala will further the lifesaving mission of St. Jude Childrens Research Hospital: Finding cures. Saving children.®

In August 1978, TKE officially joined Frater Danny Thomas in the fight against childhood cancer by raising money for St. Jude Childrens Research Hospital. Now, 30 years later, TKE is recommitted to this amazing cause and will strive to continue the pledge set forth by our fellow Fraters. Even though Danny died in February 1991, his vision for St. Jude lives on.. Danny Thomas formed ALSAC to raise funds solely for St. Jude Childrens Research Hospital. And while the hospital struggled to sustain growth during the early years, support from individuals and organizations like TKE helped keep it afloat. Danny noted in the Fall 78 edition of THE TEKE, Every time wed think we had enough for next year, the researchers would come up with a bigger need. Fortunately, with people like my Fraters in TKE, we have been able to accomplish what we initially thought was a hopeless task.. Though this was the era when fraternities were viewed as wild and reckless, Danny noted how Tau Kappa Epsilon seemed to be ...

In August 1978, TKE officially joined Frater Danny Thomas in the fight against childhood cancer by raising money for St. Jude Childrens Research Hospital. Now, 30 years later, TKE is recommitted to this amazing cause and will strive to continue the pledge set forth by our fellow Fraters. Even though Danny died in February 1991, his vision for St. Jude lives on.. Danny Thomas formed ALSAC to raise funds solely for St. Jude Childrens Research Hospital. And while the hospital struggled to sustain growth during the early years, support from individuals and organizations like TKE helped keep it afloat. Danny noted in the Fall 78 edition of THE TEKE, Every time wed think we had enough for next year, the researchers would come up with a bigger need. Fortunately, with people like my Fraters in TKE, we have been able to accomplish what we initially thought was a hopeless task.. Though this was the era when fraternities were viewed as wild and reckless, Danny noted how Tau Kappa Epsilon seemed to be ...

Several studies have demonstrated that LncRNAs can play major roles in cancer development. The creation of a catalog of LncRNAs expressed in T cell acute lymphoblastic leukemia (T-ALL) is thus of particular importance. However, this task is challenging as LncRNA expression is highly restricted in time and space manner and thus may greatly differ between samples. We performed a systematic transcript discovery in RNA-Seq data obtained from T-ALL primary cells and cell lines. This led to the identification of 2560 novel LncRNAs. After the integration of these transcripts into a large compendium of LncRNAs (n = 30478) containing both known LncRNAs and those previously described in T-ALLs, we then performed a systematic genomic and epigenetic characterization of these transcript models demonstrating that these novel LncRNAs share properties with known LncRNAs. Finally, we provide evidence that these novel transcripts could be enriched in LncRNAs with potential oncogenic effects and identified a subset of

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ORIGINAL ARTICLES Minerva Pediatrica 2001 April;53(2):87-94. Cardiac involvement in Kawasaki disease. Our experience. Sciacca P., Falsaperla R., Barone P., Tornambene G., Mattia C., Marletta M., Betta P., Distefano G.. Abstract PDF. ORIGINAL ARTICLES Minerva Pediatrica 2001 April;53(2):95-8. Multicystic dysplastic kidney and contralateral vesicoureteral reflux. Renal growth. Fanos V., Sinaguglia G., Vino L., Pizzini C., Portuese A.. Abstract PDF. REVIEWS Minerva Pediatrica 2001 April;53(2):99-106. Respiratory tract infections caused by respiratory syncytial virus in children. Diagnosis and treatment. Van Woensel J. B. M., Kimpen J. L. L., Brand P. L. P.. Abstract PDF. REVIEWS Minerva Pediatrica 2001 April;53(2):107-20. Assessment and measurement of pain in infants and children. Trapanotto M., Benini F., Agosto C., Pardi C., Lazzarin P., Zacchello F.. Abstract PDF. SPECIAL ARTICLES Minerva Pediatrica 2001 April;53(2):121-8. Experience of comic relief in pediatric hospital. Bruschettini P., ...