813 research outputs found
New Approaches to the Management of Adult Acute Lymphoblastic Leukemia
No full textTraditional treatment regimens for adult acute lymphoblastic leukemia, including allogeneic hematopoietic cell transplantation, result in an overall survival of approximately 40%, a figure hardly comparable with the extraordinary 80% to 90% cure rate currently reported in children. When translated to the adult setting, modern pediatric-type regimens improve the survival to approximately 60% in young adults. The addition of tyrosine kinase inhibitors for patients with Philadelphia chromosome-positive disease and the measurement of minimal residual disease to guide risk stratification and postremission approaches has led to additional improvements in outcomes. Relapsed disease and treatment toxicity-sparing no patient but representing a major concern especially in the elderly-are the most critical current issues awaiting further therapeutic advancement. Recently, there has been considerable progress in understanding the disease biology, specifically the Philadelphia-like signature, as well as other high-risk subgroups. In addition, there are several new agents that will undoubtedly contribute to additional improvement in the current outcomes. The most promising agents are monoclonal antibodies, immunomodulators, and chimeric antigen receptor T cells, and, to a lesser extent, several new drugs targeting key molecular pathways involved in leukemic cell growth and proliferation. This review examines the evidence supporting the increasing role of the new therapeutic tools and treatment options in different disease subgroups, including frontline and relapsed or refractory disease. It is now possible to define the best individual approach on the basis of the emerging concepts of precision medicine
Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
No full textPh-Positive Acute Lymphoblastic Leukemia Until recently, Ph-positive ALL was very aggressive and difficult to treat. Current frontline therapy, based on tyrosine kinase inhibitors, glucocorticoids, and blinatumomab, has increased survival, with high-level clearance of measurable tumor cells
How has the management of Ph(+) acute lymphoblastic leukemia (ALL) changed over the years
No full textFor decades, Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been considered the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL and, in the elderly, it accounts for approximately 50% of cases. The introduction of tyrosine kinase inhibitors (TKIs) has led to obtain complete hematologic remissions (CHR) in virtually all patients, to improve disease-free survival and overall survival, and to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT). Thus, the current management of adult Ph+ ALL patients is based on the use of a TKI, with or without systemic chemotherapy, followed by an allo-SCT, which still remains the only curative option. Monitoring of minimal residual disease allowed a better stratification of patients, and also enabled to redefine the role of autologous stem cell transplant for patients who do not have a donor or are unfit for an allo-transplant. The main clinical challenges are today represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, including novel TKIs and/or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered
Management of adult Ph-positive acute lymphoblastic leukemia
No full textPhiladelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been regarded for decades as the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL, and increases progressively with age. The introduction of tyrosine kinase inhibitors (TKIs) has enabled to obtain complete hematologic remissions (CHRs) in virtually all patients, including the elderly, to improve disease-free survival and overall survival, as well as to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT).The current management of adult Ph+ ALL patients relies on the use of a TKI with or without chemotherapy followed by an allo-SCT, which still remains the only curative option. Minimal residual disease screening is permitting not only a better stratification of patients, but has also allowed to reconsider the role of autologous stem cell transplant for a set of patients who do not have a donor or are not eligible for an allo-SCT. At present, clinical challenges are represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, comprising novel TKIs or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered in order to overcome resistance
Modern Management Options for Ph+ ALL
No full textImpressive advances have been achieved in the management of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) since the initial concurrent use of imatinib and standard chemotherapy. The attenuation of chemotherapy has proven to be equally effective and less toxic, the use of third generation TKI upfront has improved the frequency of complete molecular response and the survival rate, and the combination of tyrosine kinase inhibitors with immunotherapy has further increased the rate of molecular response to 70–80% after consolidation, which has been translated into a survival rate of 75–90% in recent trials. As a result of these improvements, the role of allogeneic hematopoietic stem cell transplantation is being redefined. The methodology of measurable residual disease assessment and the detection of ABL1 mutations are also improving and will contribute to a more precise selection of the treatment for newly diagnosed and relapsed or refractory (R/R) patients. Finally, new compounds combined with immunotherapeutic approaches, including cellular therapy, are being used as rescue therapy and will hopefully be included in first line therapy in the near future. This article will review and update the modern management of patients with Ph+ ALL
Genomic analysis in lymphoid leukemias.
No full textThe introduction of microarray analysis represents a revolution in the scientific field, allowing to investigate thousand of genes in a single experiment. Important biological insights have been revealed by this technique in several tumors: in acute lymphoblastic leukemia (ALL), these studies have allowed to identify specific patterns associated with known molecular abnormalities, as well as with phenotypic characteristics and with different prognostic features. In chronic lymphocytic leukemia (CLL), this approach has helped to dissect that this disease is a single entity with distinct variants that are characterized by a diverse IgVH mutational status, that can be discriminated by a small set of genes, has allowed to define a similarity between this disease and memory B cells and has also led to hypothesize that CLL cells from IgVH unmutated patients may be continuously stimulated in vivo, thus showing a gene profile that is reminiscent of the B cell receptor. In multiple myeloma (MM), gene expression profiles has provided insights into the disease and has offered the opportunity of stratifying patients according to the degree of aggressiveness of the disease. Current efforts are directed to the identification of patterns that may distinguish patients with a different outcome, thus providing useful prognostic information and to design experiments that may allow the identification of new therapeutic targets
Myeloid/T-cell acute lymphoblastic leukemia in children and adults
No full textUntil recently, few molecular aberrations were recognized in T-cell acute lymphoblastic leukemia (T-ALL) and they were restricted to aberrations involving the T-cell receptor (TCR). The introduction of powerful technologies has allowed to identify novel rearrangements. In this context, we have performed a gene expression profiling analysis on a relatively large cohort (n=69) of adult patients with a diagnosis of T-ALL. By unsupervised clustering, we identified 5 subgroups. Of these, one branch included 7 patients (10%) whose gene expression profile resembled that of AML. These cases were characterized by the overexpression of a large set of myeloid-related genes, as well as of miR-223. Finally, these patients appear to have an unfavorable clinical course. This newly identified subset of T-ALL cases partly resembles the so-called ETP (early T-precursor) pediatric subgroup: both age groups have in fact a peculiar gene expression profile, an unfavorable outcome and an incidence of about 10%
Sabina Murray, 30th Annual ODU Literary Festival
No full textSabina Murray is the award-winning author of the novels Slow Burn, and A Carnivore’s Inquiry, and the story collection The Caprices. A former Michener Fellow at the University of Texas and Bunting Fellow at the Radcliffe Institute of Harvard University, she received the PEN/Faulkner Award for Fiction in 2003. Murray’s stories have appeared in Ploughshares, Ontario Review, the New England Review, and other literary journals. Currently, she teaches in the MFA program at the University of Massachusetts, Amherst
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