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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic cell transplantation from a histocompatible sibling is generally recommended for patients with acute myeloid leukemia in first remission with intermediate or high risk disease. Two-thirds of patients lack a matched sibling raising the question of the utility of matched unrelated transplantation for such patients. Retrospective studies from single institutions and registry data report 44-50% disease-free survival at 5-years following ablative unrelated donor transplantation for adults. The German AML 01/99 is the only prospective study evaluating the utility of matched related and unrelated transplantation for AML patients in first remission with high risk disease and reported 4-year survival of 68% with matched related transplants, 56% with matched unrelated transplants and 23% with autografting. Thus, results suggest that for patients with AML in first remission with high risk features (as determined by cytogenetics or >5% blasts on day 15 of induction) who lack matched siblings, unrelated donor transplantation should be considered. Current challenges are to improve our ability to identify those patients most likely to benefit from early transplantation, to better select donors, and to develop transplant preparative regimens that are safer and more effective.
Best Pract Res Clin Haematol 2007 Mar
PMID:Hematopoietic cell transplantation from unrelated donors for treatment of patients with acute myeloid leukemia in first complete remission. 1733 56

Since 1986, the University of California San Francisco has developed novel approaches to autologous transplantation for acute myeloid leukemia (AML). Strategies have included intensive preparative regimens using busulfan and etoposide, and evolving strategies for pre-transplant consolidation and stem cell collection. Treatment-related mortality has been low (<5%), and after problems with slow engraftment and extended mucosal and skin toxicity in initial studies using 4-hydroperoxycyclophosphamide (4-HC)-purged bone marrow, peripheral blood autologous stem cell transplantation (ASCT) has been well tolerated even in older patients. In particular, careful attention to avoiding neurotoxicity associated with the use of high-dose cytarabine has limited dropout rates. Long-term event-free survival (EFS) has been excellent in first remission (CR1) cytogenetically favorable groups, particularly with post-transplant treatment for acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA; EFS 88%). ASCT in advanced disease showed overall long-term EFS of 44%; patients with APL in second remission achieved long-term EFS of 64%. Even among those failing primary induction, after remission induction with an alternative regimen, EFS was 61%. ASCT appears to be a treatment of choice for those in APL CR2, and offers some curative potential for AML CR2. The role of ASCT for those in CR1 is less clear, in part because high dropout rates in large randomized studies complicates interpretation of those studies. New directions for ASCT in the treatment of AML should focus on improving therapy, including calibrated intensification of induction regimens using plasma-kinetics targeting of dosages and the development and incorporation of immunotherapies into consolidation regimens.
Best Pract Res Clin Haematol 2007 Mar
PMID:The role of autologous transplantation for acute myeloid leukemia in first and second remission. 1733 57

In allogeneic transplantation the donor-recipient sex combination plays a role in outcome. In large retrospective registry studies of several thousands of patients with aplastic anemia, chronic myelocytic leukemia (CML), acute myelocytic leukemia (AML), and multiple myeloma, chronic graft-versus-host disease (cGVHD) was more frequent and transplant-related mortality (TRM) higher in males with a female donor (F-->M) than in other donor-recipient sex combinations. Graft rejection was more frequent in females with a male donor (M-->F) in aplastic anemia, and a graft-versus-tumor effect (GVT) was documented as a reduced relapse rate in F-->M in CML, AML and multiple myeloma. The overall survival was adversely affected in F-->M in aplastic anemia, AML and CML and in M-->F in aplastic anemia. These results support the view that donor T cells specific for male minor histocompatiblity antigens encoded by Y-chromosome genes contribute to GVHD, graft rejection, GVT and survival in sex-mismatched transplants.
Best Pract Res Clin Haematol 2007 Jun
PMID:Risk assessment in haematopoietic stem cell transplantation: impact of donor-recipient sex combination in allogeneic transplantation. 1744 58

The identification of FLT3 mutations across a range of the cytogenetic subgroups of AML has opened up the possibility of a targeted therapeutic approach with broad applicability. Four agents are currently in clinical trials, at least 3 of which have both sufficient activity against AML and sufficiently acceptable toxicity profiles to support continued efforts to refine their inclusion into therapeutic regimens for AML. Better understanding of the genetics of inherent and acquired resistance is needed to guide development of second-generation agents. Optimizing the integration of FLT3 inhibitor therapy with chemotherapy has the potential both to decrease toxicity and improve response.
Best Pract Res Clin Haematol 2008 Mar
PMID:Can FLT3 inhibitors overcome resistance in AML? 1834 8

Gene expression profiling, the simultaneous measurement of the global patterns of gene expression in cells using microarray technologies, has held promise to improve diagnosis, risk classification, and outcome prediction in acute leukemias as well as in other human cancers. But how much has gene expression profiling impacted or improved current diagnosis and risk classification schemes and therapeutic targeting in acute myeloid leukemia (AML)? To date, gene expression profiling of AML has largely confirmed the presence of well-established recurring cytogenetic abnormalities, such as translocations, deletions, point mutations, or normal karyotypes, and has led to the identification of sets of genes reflective of these abnormalities. The use of expression profiling and statistical modeling to develop molecular classifiers that improve outcome prediction beyond traditional prognostic variables or the targeting of patients to specific therapies or transplantation has been less successful. Similarly, expression profiling has not led to the identification of many novel therapeutic targets in AML. Using advanced statistical modeling techniques, our group has focused on expression profiling in adult AML patients with poor risk features in order to identify novel cluster groups and potential targets for therapy in this highly resistant form of disease. To further advance the application of gene expression profiling and other comprehensive genomic and phosphoproteomic techniques to the study of AML, it would be ideal for the NCI Cooperative Groups to register all patients to common or intergroup collaborative clinical trials or registration studies in order to develop large, well-characterized cohorts of uniformly treated patients for future research studies.
Best Pract Res Clin Haematol 2008 Mar
PMID:Has gene expression profiling improved diagnosis, classification, and outcome prediction in AML? 1834 9

Today, treatment of patients with acute myeloid leukemia (AML) remains predominantly a "one-fits-all" approach with intensive cytarabine-based chemotherapy as the mainstay, but we are finally beginning to reap the rewards of decades of basic, translational, and clinical research. Developing individualized, "targeted" therapy for each AML patient based on unique molecular features of disease remains a daunting goal, yet one that we can now begin to envision. Hypothesis-based study designs--from preclinical/laboratory experiments to phase 1 and subsequent efficacy trials--provide the foundation for advances in the diagnosis, risk stratification, and treatment of patients with AML. The following is an outline of several key areas of ongoing AML research.
Best Pract Res Clin Haematol 2008 Mar
PMID:New approaches in acute myeloid leukemia. 1834 10

Adults 18-60 years old with acute myelogenous leukemia (AML) should undergo some form of postremission therapy, however, how much and what kinds of postremission chemotherapy remain unclear. In contrast, for older patients more than one cycle of chemotherapy postremission does not appear justified except perhaps in those rare patients with favorable cytogenetics who are young enough to tolerate standard therapy and in whom there is still an option for cure. Routine postremission therapy is not justifiable for those with unfavorable cytogenetics. However, the median age of AML patients approaches 70 years; this is a group of patients who often reach minimal disease, but with a median disease-free survival of only 4 to 5 months, regardless of their cytogenetics, and are therefore an ideal patient group for clinical studies. Older patients have limited tolerance for intensive regimens, although relatively nontoxic agents exist that can be explored. The issue of maintenance remains open.
Best Pract Res Clin Haematol 2008 Mar
PMID:Consolidation therapy: what should be the standard of care? 1834 12

Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.
Best Pract Res Clin Haematol 2008 Mar
PMID:Is it important to decipher the heterogeneity of "normal karyotype AML"? 1834 11

For older adults (ie, those age 60 and above) with acute myelogenous leukemia, patient and clinician have three choices: standard therapy, ie, a "3+7" regimen or low-dose ara-C, investigational therapy, or palliative care. Investigational treatments sponsored by pharmaceutical companies tend to exclude the 10-20% of older patients who have a poor performance status (Zubrod >2), an increased bilirubin, or creatinine (>1.9 mg/ml) and who are thereby unlikely to do well with standard therapy. However, even excluding such patients, standard treatment offers little obvious benefit for most older patients. Nonetheless, these older patients are not uniform and can be stratified to receive investigational therapy, which is mandatory for most, or standard therapy, which is not inappropriate for some.
Best Pract Res Clin Haematol 2008 Mar
PMID:Older adults: should the paradigm shift from standard therapy? 1834 13

Current strategies for incorporating hematopoietic cell transplantation into the treatment of adults with AML are based predominantly on pre-treatment patient, donor and disease characteristics. These strategies, while useful, have significant shortcomings in that they recommend deferred transplantation for many patients who would benefit from earlier intervention and, at the same time, direct other patients who would be cured with chemotherapy alone to the more risky and toxic approach of early transplantation. Here we review the currently accepted indications for transplantation and raise the possibility that alternative approaches to incorporating transplantation into the management of adults with AML that rely predominantly on the measurement of minimal residual disease (MRD) could save additional lives without any major advance in chemotherapy or transplant technologies.
Best Pract Res Clin Haematol 2008 Mar
PMID:Incorporating hematopoietic cell transplantation (HCT) into the management of adults aged under 60 years with acute myeloid leukemia (AML). 1834 16


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