Immunotherapy for acute myeloid leukemia (AML): a potent alternative therapy.

The standard therapy of AML for many years has been chemotherapy with or without stem transplantation. However, there has not been any tangible improvement in this treatment beyond induction through chemotherapy and consolidation with allogeneic stem cell transplantation or chemotherapy. Residual AML cells which later cause relapse mostly persist even after rigorous standard therapy. It is imperative therefore to find an alternative therapy that can take care of the residual AML cells. With a better understanding of how the immune system works to destroy tumor cells and inhibit their growth, another therapeutic option immunotherapy has emerged to address the difficulties associated with the standard therapy. Identification of leukemia-associated antigens (LAA) and the fact that T and NK cells can be activated to exert cytotoxicity on AML cells have further introduced diverse immunotherapeutic development strategies. This review discusses the merits of current immunotherapeutic strategies such as the use of antibodies, adoptive T cells and alloreactive NK cell, and vaccination as against the standard therapy of AML.

Prognostic pre-transplant factors in myelodysplastic syndromes primarily treated by high dose allogeneic hematopoietic stem cell transplantation: a retrospective study of the MDS subcommittee of the CMWP of the EBMT.

Many pre-transplant factors are known to influence the outcome of allogeneic stem cell transplantation (SCT) treatment in myelodysplastic syndromes (MDS). However, patient cohorts are often heterogeneous by disease stage and treatment modalities, which complicates interpretation of the results. This study aimed to obtain a homogeneous patient cohort by including only de novo MDS patients who received upfront allogeneic SCT after standard high dose myelo-ablative conditioning. The effect of pre-transplant factors such as age, disease stage, transfusions, iron parameters and comorbidity on overall survival (OS), non-relapse mortality (NRM), and relapse incidence (RI) was evaluated in 201 patients. In this cohort, characterized by low comorbidity and a short interval between diagnosis and transplantation, NRM was the most determinant factor for survival after SCT (47 % after 2-year follow-up). WHO classification and transfusion burden were the only modalities with a significant impact on overall survival after SCT. Estimated hazard ratios (HR) showed a strongly increased risk of death, NRM and RI, in patients with a high transfusion-burden (HR 1.99; P = 0.006, HR of 1.89; P = 0.03 and HR 2.67; P = 0.03). The HR's for ferritin level and comorbidity were not significantly increased.

Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns.

Progress in the last decade has improved the understanding of leukemia biology. Molecular markers in combinations with cytogenetics have improved the risk stratification of acute myeloid leukemia (AML) and informed decision-making. In parallel, several important advances in the transplant field, such as better supportive care, improved transplant technology, increased availability of alternative donors, and reduced-intensity conditioning have improved the safety as well as access of allogeneic hematopoietic cell transplantation (HCT) for a larger number of patients. In this review, the positioning of HCT in the management of patients with AML is evaluated in view of changing risk/benefit ratios associated with both conventional treatments and transplantation, and some of the controversies are addressed in light of emerging data. Increasing data demonstrate outcomes of alternative donor transplantation approaching HLA-identical sibling donors in high-risk AML supporting the inclusion of alternative donors in trials of prospective studies evaluating post remission strategies for high-risk AML. The use of reduced-intensity conditioning has expanded the eligibility of HCT to older patients with AML, and outcome data are encouraging. Continued study of HCT versus alternative therapies is required to optimize patients' outcomes in AML.

Daily practice management of myelodysplastic syndromes in France: data from 907 patients in a one-week cross-sectional study by the Groupe Francophone des Myelodysplasies.

BACKGROUND: There is little published information on the everyday clinical management of myelodysplastic syndromes in real world practice. DESIGN AND METHODS: We conducted a cross-sectional study of all patients with myelodysplastic syndromes attending 74 French centers in a 1-week period for inpatient admission, day-hospital care or outpatient visits. RESULTS: Nine hundred and seven patients were included; 67.3% had lower-risk myelodysplastic syndromes (International Prognostic Scoring System: low or intermediate-1). Karyotype had been analyzed in 82.5% of the cases and was more often of intermediate or poor risk in patients under 65 years old compared with those who were older. Red blood cell transfusions accounted for as many as 31.4% of the admissions. Endogenous erythropoietin level was less than 500 IU/L in 88% of the patients tested. Erythroid stimulating agents had been or were being used in 36.8% of the lower risk patients, iron chelation in 31% of lower risk patients requiring red blood cell transfusions and lenalidomide in 41% of lower risk patients with del 5q. High-dose chemotherapy, hypomethylating agents, low dose cytarabine and allogeneic stem cell transplantation had been or were being used in 14.8%, 31.1%, 8.8% and 5.1%, respectively, of higher-risk patients. CONCLUSIONS: Karyotype is now assessed in most patients with myelodysplastic syndromes, and patients under 65 years old may have more aggressive disease. Apart from erythroid-stimulating agents and, in higher-risk myelodysplastic syndromes, hypomethylating agents, specific treatments are used in a minority of patients with myelodysplastic syndromes and red blood cell transfusions still represent the major reason for hospital admission.

Trends in haematopoietic cell transplantation for inborn errors of metabolism.

For the last 25 years, haematopoietic cell transplantation (HCT) has been used as effective therapy for selected inborn errors of metabolism (IEMs), mainly lysosomal storage diseases and peroxisomal disorders. The main rational for HCT in IEMs is based on the provision of correcting enzymes by donor cells within and outside the blood compartment. The ultimate goal of HCT is to achieve a normal or near-normal life and normal neurodevelopment. HCT has been performed for more than 20 diseases. Only for Hurler syndrome, X-ALD and infantile Krabbe disease, are detailed studies available suggesting that HCT is indicated for carefully selected cases. Improvement of transplantation techniques and alternative therapies may change the recommended (contra-)indications for IEM. A recent example of emerging transplantation techniques is the fast availability of unrelated cord blood (UCB). UCB makes HCT feasible in patients with rapidly progressive neurological diseases. Because of the fast availability of UCB and therefore the ability to transplant shortly after diagnosis, there is no indication for patients in a moderate/good clinical condition to receive enzyme replacement therapy (ERT; in Hurler syndrome) prior to or during HCT and can ERT only be considered in patients with poor clinical condition. Mesenchymal stem cell infusions with HCT is an emerging technique, and might be interesting in halting the remaining defects after successful HCT. Improvement in HCT techniques and novel stem cell sources will significantly impact the safety and efficacy of this therapy as well as expand the list of candidate disorders. A good functioning worldwide registry would be necessary to measure the effects of the procedures performed in more detail.

Hematopoetic stem cell transplantation for solid tumors in Europe.

BACKGROUND: Hematopoetic stem cell transplants (HSCT) are discussed as treatment options for patients with solid tumors. Transplant numbers have changed substantially over the last decade, few controlled studies are available and different opinions prevail. Objective information on current practice is needed. PATIENTS AND METHODS: Data from 27 902 HSCT for solid tumors (2% allogeneic, 98% autologous), collected by the European Group for Blood and Marrow Transplantation (EBMT) activity survey from 1991 to 2002 were used to assess trends, transplant rates and coefficient of variation of transplant rates in Europe. RESULTS: Transplant numbers increased from 536 in 1991 to 4154 in 1997 and decreased to 1913 in 2002. Indications were neuroblastoma (2504 HSCT; 9%), glioma (662 HSCT; 2%), soft tissue sarcoma (1253 HSCT; 4%), germ cell cancer (3291 HSCT; 12%), breast cancer (13 524 HSCT; 48%), Ewing's sarcoma (1896 HSCT; 7%), lung cancer (387 HSCT; 1%), ovarian cancer (845 HSCT; 3%) and other solid tumors (3540 HSCT; 14%). Allogeneic cells were used in <20 cases up to 1997; since then allogeneic HSCT increased to 159 in 2002, mainly for renal cell carcinoma. Low coefficients of variation in transplant rates (<60%) are observed for Ewing's sarcoma (<56.5%), suggesting consensus for this indication. CONCLUSIONS: These data give an overview on current practice of HSCT for solid tumors in Europe. They provide objective information for health-care providers and patient counselling.

Peripheral blood cells transplantation--a review article.

In the twelve years since the first PBSCT were reported, impressive advancements in BCT techniques have made it easy to perform, effective, less costly, rapid haematologically recoverable, reduced morbidity and mortality, shorten overall duration of cancer treatment and hospital stay. Development of high-dose chemotherapy and new novel effective antitumor drugs otherwise limited by haematological toxicities may now become possible. Treatment of haematological malignancies with purged autologous PBPCT, e.g. Ph Chromosome negative progenitor cells in CML or with immunologically manipulated allogeneic PC having preserved GVL but not GVHD action, with hopeful prospects, is now becoming possible. Tailoring of BC for ex-vivo selection and expansion of specially active T Iymphocytes, NK cells and other immune effector cells will enable adoptive immunotherapeutic approach and treatment of Minimal residual disease [MRD] after high-dose chemotherapy both in grafts and in patients. The discovery of a nonhaematopoietic, engraftment facilitator cell form donor BM may usher in further precision in GVHD prevention by purification and in adoptive immunotherapeutic approach. Therefore, it is likely that BCT will supersede BMT, though the follow-up is too short to draw conclusions.