Leukemia supplements最新文献

The introduction of Abl tyrosine kinase inhibitors (TKI; that is, imatinib, dasatinib and nilotinib) as front-line therapy completely changed the course of chronic myelogenous leukemia (CML) to the point that most of the TKI-responsive newly diagnosed CML patients can be considered 'clinically' cured and their progression into blast crisis (BC) a rare event. However, a therapy for those patients who transform is still lacking, and TKIs do not eradicate CML at the stem cell level, therefore leaving a reservoir of cancer stem cells in a dormant stage. Thus, it is not surprising that the focus of CML research has shifted significantly toward the dissection of the mechanisms regulating the survival and self-renewal of TKI-resistant Philadelphia-positive leukemic chronic phase and BC stem cells, with the ultimate goal of developing small molecules capable of selectively killing leukemic but not normal hematopoietic stem cells, thereby achieving a 'biological' cure for this disease.

The approach to treatment of acute myeloid leukemia is substantially influenced by the age of the patient. Younger patients who are arbitrarily defined as those being <60 years, although comprising the minority of all patients with the disease, will always receive an intensive approach, whereas in older patients, an initial decision as to whether an intensive approach is appropriate or not has to be made. Standard chemotherapy for many years has been '3+7', followed by consolidation with high-dose Ara-C at a daily dose level of 3 g/m(2). It remains unclear as to what number of total treatment courses is optimal. Alternatives to this standard of care will be considered.

The treatment of older patients with acute myeloid leukemia is a difficult challenge. Older adults are more likely to have comorbidities that can limit treatment options, the disease tends to be more aggressive biologically and outcomes are worse than those in younger patients. Deciding which older patients would benefit from intensive chemotherapy is difficult, and efforts are underway to improve existing risk-assessment tools. Treatment should be individualized and may include standard chemotherapy for those patients who have none or at most one adverse factor, or investigational agents for those presenting with multiple poor-risk features. Low-intensity therapies are recommended for those patients who are deemed too frail to tolerate myelosuppressive regimens.

Viral infections remain one of the most frequent complications in patients with hematological malignancies, especially in those receiving an allogeneic stem cell transplantation. Viral infections result from reactivation of latent infection rather than from acquisition of new infection. Infections caused by herpes viruses, including cytomegalovirus and Epstein-Barr virus, respiratory viruses and hepatitis B virus are frequently associated with high morbidity and mortality in the immunocompromised host. Major advances have been made primarily by the availability of rapid diagnostic tests and the introduction of potent antiviral compounds into clinical practice.

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by dysplasia in one or more cell lines, ineffective hematopoiesis and variable risk of progression to acute myeloid leukemia. In the past few years, important steps have been taken in characterizing the molecular basis of MDS. More recently, somatic mutations in genes encoding core components of the RNA splicing machinery have been detected in high proportions of MDS patients, and are shown to be founding mutations in many instances. These mutations have different clinical significance, and their incorporation into current stratification systems might improve risk assessment in MDS.

Acute myeloid leukemia (AML) is a heterogeneous disease increasing in frequency owing to an aging population. Decisions on intensive induction treatments, intensification and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task; here we examine those variables useful in assessing prognosis for a patient with non-acute promyelocitic AML focusing on core binding factor leukemia. In clinical practice, when counseling an individual patient with AML, a range of well-known clinical variables (age, performance status and tumor burden) and genetic variables (cytogenetic and gene mutation) must be considered to better define the prognostic risk.

Fungi are typically opportunistic pathogens. Formerly, limitations in diagnostic techniques explain why invasive fungal infections are usually detected in a late stage of their development. Therefore, traditional guidelines dictate antifungal treatment for all patients with persisting fever. This is not longer justifiable in view of the potential adverse events and the economical burden associated with the use of the new antifungal drugs in an era with improved diagnostic tools. Amphotericin B has been the drug of choice for invasive fungal infections for more than 30 years. Owing to nephrotoxicity, its use in neutropenic patients has been largely abandoned in favor of a lipid formulation of amphotericin B, of which only liposomal amphotericin B has been scientifically tested in the first-line treatment of aspergillosis. Azoles constitute an acceptable alternative to intravenous amphotericin B for many invasive fungal infections.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, as some patients progress rapidly toward the more advanced studies, whereas others survive for a long period without the need for treatment. This heterogeneity of clinical course was somehow unexplained until studies on the CLL cell features disclosed that the CLL clones were heterogeneous and were characterized by different phenotypic and genotypic features in the different patients. On the basis of these observations, it was determined in retrospective studies that clones characterized by unmutated IGHV genes, and/or CD38 and/or ZAP-70 expression conferred a more severe prognosis to the CLL patients. Here, we present data on prospective studies carried out on Binet A-stage patients, in whom the markers were determined at diagnosis and their predictive value was assessed in comparison with chromosomal abnormalities and gene expression or micro RNA profiles. In addition, hypothesis on the potential pathogenetic role of these markers will be presented.

Tyrosine kinase inhibitors (TKIs) of BCR-ABL have turned chronic myeloid leukemia (CML) from a deadly disease into a chronic ailment. Unfortunately, evidence is accumulating that TKIs are not curative, since CML stem cells are not addicted to BCR-ABL, and persist despite TKI therapy. On closer view this is not surprising, as it reflects fundamental principles of CML pathogenesis. Strategies to eradicate CML stem cells will most likely be based on synthetic lethality though parallel inhibition of BCR-ABL and other critical pathways.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by t(15;17) and a life-threatening coagulopathy. Once highly fatal, nowadays standard treatment approaches with all-trans retinoic acid (ATRA) along with chemotherapy allows curing up to 80-85% of cases. In the past decade, arsenic trioxide used alone or in combination with ATRA has demonstrated high efficacy in APL, and is currently regarded as the gold standard for treatment of relapsed cases. Chemotherapy-free approaches based on the combination of arsenic trioxide and ATRA are currently being tested against standard ATRA and chemotherapy in randomized clinical trials for frontline therapy of APL.