Leukemia supplements最新文献

Stem cell transplantation (SCT) has been used in the treatment of multiple myeloma (MM) for decades and has become a standard of care for newly diagnosed MM patients. However, several important questions remain regarding the optimal use of SCT, particularly in light of the many recent advances in the treatment of MM. Bortezomib-based therapy or, in some cases, lenalidomide-based therapy should be considered as an induction therapy in transplantation-eligible patients. Efforts to improve upon the efficacy and safety of standard transplantation regimens (that is, high-dose melphalan) are also underway. Most published studies on the use of tandem autologous SCT were conducted before the advent of novel agents, such as thalidomide, lenalidomide and bortezomib, making it difficult to establish the current role of tandem SCT. Allogeneic SCT continues to be evaluated in clinical trials, and may have an important role in the treatment of transplantation-eligible patients with suitable donors. Post-transplantation consolidation and maintenance therapy using novel agents should be considered to improve outcomes in patients who fail to achieve a complete response following SCT. Patients in remission should be advised that continued therapy has been shown to prolong remission, improve quality of life and extend survival. Additional data on the optimal approach to post-transplantation therapy are needed. New strategies in development aimed at improving patient selection, safety and efficacy of SCT are likely to improve future outcomes.

Although multiple myeloma (MM) remains an incurable disease, the advent of novel treatment paradigms has improved survival outcomes in the past two decades. This includes widespread use of high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) and the development of the novel agents thalidomide, lenalidomide and bortezomib. The efficacy and tolerability of these novel agents have allowed for the exploration of continuous therapy approaches. Maintenance therapy after HDT-ASCT, for example, may help prolong progression-free survival by providing sustained control of residual disease. Trials are also under way to evaluate lenalidomide in patients with high-risk smoldering MM, with the aim of delaying progression to symptomatic MM. Other research is focusing on improving HDT-ASCT protocols and integrating novel agents, such as bortezomib, as an induction or consolidation therapy. Despite these advances, more effective strategies are needed, particularly for the management of older, less fit patients who are ineligible for HDT-ASCT. Preliminary results on the use of lenalidomide maintenance therapy in elderly patients are encouraging. Taken together, these observations indicate that in this era of novel agents, optimal treatment of MM requires a long-term perspective that focuses on providing sustained disease control while maintaining quality of life.

Next-generation whole-exome sequencing has revealed two novel genes, namely NOTCH1 and SF3B1, whose mutations predict poor outcome and preferentially associate with chemorefractory chronic lymphocytic leukemia (CLL). Analysis of 539 CLL cases documents that NOTCH1 mutations i) represent one of the most frequent cancer gene mutations involved at presentation; ii) cluster with cases harboring trisomy 12 and tend to be mutually exclusive with TP53 disruption among genetic subgroups; iii) identify high-risk patients showing poor survival similar to that associated with TP53 abnormalities; and iv) exert a prognostic role independent of widely accepted clinical and genetic risk factors. Mutations of SF3B1, a splicing factor that is a critical component of the spliceosome, recurrently associate with fludarabine-refractory CLL, occur at a low rate at CLL presentation and have a minor role in Richter transformation, corroborating the notion that CLL histological shift is molecularly distinct from chemorefractory progression without the Richter transformation.

Although hematopoietic stem cell transplantation (allogeneic SCT (allo-SCT)) is the treatment of choice for many aggressive hematological malignancies, the role of allo-SCT in chronic lymphocytic leukemia (CLL) is still a matter of debate and can be considered one of the more important challenges for the next decade. In the era of novel drugs and humanized antibodies, the long-term outcome of patients has improved, and a critical reappraisal of autologous and allo-SCT in CLL treatment is warranted.

The first-line treatment of chronic myeloid leukemia is based on the three currently available tyrosine kinase inhibitors (TKIs), namely imatinib, nilotinib and dasatinib. Nilotinib and dasatinib are more potent, and it is predicted that, in comparison with imatinib, they can reduce the risk of progression and increase the number of the patients who can discontinue the treatment without relapsing. Other TKIs are still being developed and may help to improve treatment options further on. Hydroxyurea has no longer a role. Allogeneic stem cell transplantation is the treatment of choice for the advanced phases, and in case of resistance to at least two TKIs.

Cord blood is an unlimited source of hematopoietic stem cells (HSCs) for allogeneic HSC transplant. Since the first human cord blood transplant performed 20 years ago, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic HSC transplant. More than 500 000 cord blood units are now available for international exchange of cord blood units. A global network of cord blood banks and transplant centers has been established for a common inventory and study of clinical outcomes. Results of unrelated allogeneic cord blood transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated bone marrow transplant, cord blood has several advantages including prompt availability of the transplant, decrease of graft versus host disease and better long-term immune recovery resulting in a similar long-term survival. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. Progresses in this field are expected to facilitate engraftment including ex vivo expansion of stem cells, intra-bone injection of cord blood cells and double cord blood transplants.

Acute lymphoblastic leukemia (ALL) in adults is currently associated with an overall survival rate of around 40% at 5 years. This is an unsatisfactory result that makes it imperative to dissect further the biology of the disease in order to identify highly specific therapeutic targets to implement selectively the cure rate. The recognition of discrete ALL subsets followed by the application of risk-oriented therapies has been a major achievement over the past 30 years.

Studies on hematopoietic stem cells have provided several critical insights in the biology of stem cells in general; as mature blood cells are generally short lived, stem cells are in fact required to guarantee, throughout the life of an organism, the replenishment of differentiated blood cells by the generation of multi-lineage progenitors and precursors committed to individual hematopoietic lineages. Similarly, acute myeloid leukemia has been considered as a model system to study cancer stem cells. This presentation illustrates some recent results obtained by our group with regard to both normal and leukemic stem cells.

Despite significant advances in the frontline treatment of chronic lymphocytic leukemia (CLL), patients eventually experience disease progression. Treatment selection of relapsed disease depends upon a variety of factors, including patient age, performance status, duration of response to initial therapy, type of prior therapy, disease-related manifestations and genetic abnormalities within the CLL cells. This presentation offers synthetic overview of the options in this field.

The purpose of evaluating prognostic factors in acute lymphoblastic leukemia is, first, to stratify patients into adverse- or good-risk groups, second, to determine different treatment options accordingly and, third, to evaluate their potential outcome. Prognostic factors are particularly relevant for disease-free survival and overall survival.