Biomedical subjects

Elizabeth Raetz

Publications and source records attributed to Elizabeth Raetz.

5 recordsLinked to original sources

PubMed2006

Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)-containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.

Adolescent↗

PubMed2005

State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays in childhood lymphoma: summary report of workshop at the First International Symposium on childhood and adolescent non-Hodgkin lymphoma, April 9, 2003, New York City, NY.

BACKGROUND: A significant number of studies describe the cytogenetics and molecular genetics of adult non-Hodgkin lymphoma (NHL); however, similar knowledge is lacking regarding pediatric NHL. METHODS: A workshop to discuss the "State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays" in pediatric NHL was held in conjunction with the First International Symposium on Childhood and Adolescent Non-Hodgkin Lymphoma on April 9, 2003 in New York City. RESULTS: Cytogenetic characteristics of pediatric NHL include 14q11.2 rearrangements in T-cell lymphoblastic leukemia/lymphomas (LBL), ALK rearrangements in anaplastic large cell lymphomas (ALCL), and CMYC translocations in both Burkitt and Burkitt-like lymphomas (BL/BLL). Pediatric diffuse large B-cell lymphoma (DLBCL) is cytogenetically different from DLBCL in adults, suggesting a different disease in children. Microarray studies demonstrate three types of T-cell leukemia, the leukemic counterpart of LBL, that block T-cell differentiation at different stages of T-cell development, corresponding to LYL, TAL1, and HOX-expressing leukemias. ALCL cell lines have a unique expression profile compared to normal T-cells. Germinal centers of BL have CMYC expression signatures, indicating that CMYC expression is ectopic and does not reflect the physiology of the normal cell counterpart. CONCLUSIONS: Additional cytogenetic, molecular and microarray investigations of NHL in children are vital to better understand these diseases, their etiology, and differences from adult NHL. A greater understanding of pediatric NHL will lead to disease-specific and patient-individualized therapies of these diseases.

Adolescent↗

PubMed2005

Childhood and adolescent non-Hodgkin lymphoma: new insights in biology and critical challenges for the future.

Pediatric non-Hodgkin lymphoma (NHL) is a common and fascinating group of diseases with distinctive underlying genetic events that characterize the major histologic subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma, anaplastic large cell lymphoma and lymphoblastic lymphoma. With systematic improvements in therapy over recent decades, the vast majority of children with NHL of all subtypes are now cured. The similarities and differences between adult and childhood presentations of disease, and whether or not some subtypes of NHL and leukemia are the same or different disease entities, are interesting questions that will be addressed with advances in our understanding of the molecular and genetic bases of these diseases. As is the case with other pediatric malignancies, growing emphasis is now being placed on the development of less toxic, targeted therapeutic approaches, and this review highlights some of the biological discoveries that will potentially open these avenues.

Adolescent↗

PubMed2003

B large-cell lymphoma in children and adolescents.

The prognosis of advanced B-large cell lymphoma (B-LCL) in children and adolescents has improved dramatically over the past 25 years (30-40% to 80-90% 5-year event-free survival (EFS)). Using strategies of treatment allocation based upon risk of disease recurrence, the total duration of therapy has been successfully reduced for many patients, and the prior requirement for radiotherapy largely eliminated. Instead of 18-30 months of combined chemotherapy and radiotherapy, current therapy has been decreased to between 6 weeks and 6 months of intensive chemotherapy. Multiagent chemotherapeutic approaches have been optimized with the use of moderate to high-dose methotrexate and further intensification with cytarabine and etoposide. The prognosis for children and adolescents who progress or relapse on current therapy for B-LCL, however, has decreased over the past 25 years with approximately 80% or 90% surviving at the present time. B-LCL in children and adolescents uniformly expresses CD20 and CD22 surface antigens. New treatment strategies employing targeted monoclonal antibody therapy combined with chemotherapy and targeted conjugated monoclonal antibody therapy conjugated with radioactive compounds and toxins are currently being investigated. Future studies utilizing immunophenotyping, cytogenetics, molecular genetics, and gene expression profiles (microarray) are required to better define the biological heterogeneity and differential clinical outcomes among children and adolescents with B-LCL.

Adolescent↗

PubMed2003

Pediatric acute lymphoblastic leukemia.

The outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically with current therapy resulting in an event free survival exceeding 75% for most patients. However significant challenges remain including developing better methods to predict which patients can be cured with less toxic treatment and which ones will benefit from augmented therapy. In addition, 25% of patients fail therapy and novel treatments that are focused on undermining specifically the leukemic process are needed urgently. In Section I, Dr. Carroll reviews current approaches to risk classification and proposes a system that incorporates well-established clinical parameters, genetic lesions of the blast as well as early response parameters. He then provides an overview of emerging technologies in genomics and proteomics and how they might lead to more rational, biologically based classification systems. In Section II, Drs. Mary Relling and Stella Davies describe emerging findings that relate to host features that influence outcome, the role of inherited germline variation. They highlight technical breakthroughs in assessing germline differences among patients. Polymorphisms of drug metabolizing genes have been shown to influence toxicity and the best example is the gene thiopurine methyltransferase (TPMT) a key enzyme in the metabolism of 6-mercaptopurine. Polymorphisms are associated with decreased activity that is also associated with increased toxicity. The role of polymorphisms in other genes whose products play an important role in drug metabolism as well as cytokine genes are discussed. In Sections III and IV, Drs. James Downing and Cheryl Willman review their findings using gene expression profiling to classify ALL. Both authors outline challenges in applying this methodology to analysis of clinical samples. Dr. Willman describes her laboratory's examination of infant leukemia and precursor B-ALL where unsupervised approaches have led to the identification of inherent biologic groups not predicted by conventional morphologic, immunophenotypic and cytogenetic variables. Dr. Downing describes his results from a pediatric ALL expression database using over 327 diagnostic samples, with 80% of the dataset consisting of samples from patients treated on a single institutional protocol. Seven distinct leukemia subtypes were identified representing known leukemia subtypes including: BCR-ABL, E2A-PBX1, TEL-AML1, rearrangements in the MLL gene, hyperdiploid karyotype (i.e., > 50 chromosomes), and T-ALL as well as a new leukemia subtype. A subset of genes have been identified whose expression appears to be predictive of outcome but independent verification is needed before this type of analysis can be integrated into treatment assignment. Chemotherapeutic agents kill cancer cells by activating apoptosis, or programmed cell death. In Section V, Dr. John Reed describes major apoptotic pathways and the specific role of key proteins in this response. The expression level of some of these proteins, such as BCL2, BAX, and caspase 3, has been shown to be predictive of ultimate outcome in hematopoietic tumors. New therapeutic approaches that modulate the apoptotic pathway are now available and Dr. Reed highlights those that may be applicable to the treatment of childhood ALL.

Child↗