Twenty Years of Unrelated Donor Hematopoietic Cell Transplantation for Adult Recipients Facilitated by the National Marrow Donor Program
ABSTRACT For more than 20 years the National Marrow Donor Program has facilitated unrelated donor hematopoietic cell transplants for adult recipients. In this time period, the volunteer donor pool has expanded to nearly 12 million adult donors worldwide, improvements have occurred in the understanding and technology of HLA matching, there have been many changes in clinical practice and supportive care, and the more common graft source has shifted from bone marrow (BM) to peripheral blood stem cells (PBSCs). The percentage of older patients who are receiving unrelated donor transplants is increasing; currently over 1 in 10 adult transplant recipients is over the age of 60 years. Chronic myelogenous leukemia (CML) was previously the most common diagnosis for unrelated donor transplantation, but it now comprises less than 10% of transplants for adult recipients. Transplants for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and myelodysplastic syndromes (MDS) all outnumber CML. Treatment-related mortality (TRM) has declined significantly over the years, particularly in association with myeloablative transplant preparative regimens. Correspondingly, survival within each disease category has improved. Particularly gratifying are the results in severe aplastic anemia (AA) where 2-year survival has doubled in just 10 years.
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ABSTRACT: Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Philadelphia chromosome-positive (Ph(+)) patients with hemangioblast property. Here, we showed that CML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for CML.Journal of Experimental & Clinical Cancer Research 05/2011; 30(1):47. DOI:10.1186/1756-9966-30-47 · 3.27 Impact Factor
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ABSTRACT: Patients and physicians may defer unrelated donor hematopoietic cell transplantation (HCT) as curative therapy due to mortality risk associated with the procedure. Therefore, it is important for physicians to know the current outcomes data when counseling potential candidates. To provide this information, we evaluated 15,059 unrelated donor HCT recipients between 2000-2009. We compared outcomes before and after 2005 for four cohorts: age <18 years with malignant diseases (N=1,920), 18-59 years with malignant diseases (N=9,575), ≥60 years with malignant diseases (N=2,194), and non-malignant diseases (N=1,370). Three-year overall survival in 2005-2009 was significantly better in all four cohorts (<18 years: 55% vs. 45%, 18-59 years: 42% vs. 35%, ≥60 years: 35% vs. 25%, non-malignant diseases: 69% vs. 60%, P<0.001 for all comparisons). Multivariate analyses in leukemia patients receiving HLA 7-8/8 matched transplants showed significant reduction in overall and non-relapse mortality in the first 1-year after HCT among patients transplanted in 2005-2009; however, risks for relapse did not change over time. Significant survival improvements after unrelated donor HCT have occurred over the recent decade and can be partly explained by better patient selection (e.g., HCT earlier in the disease course and lower disease risk), improved donor selection (e.g., more precise allele-level matched unrelated donors) and changes in transplant practices.Biology of Blood and Marrow Transplantation 10/2014; 21(1). DOI:10.1016/j.bbmt.2014.10.001 · 3.35 Impact Factor
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ABSTRACT: Problem Identification: Many patients undergoing hematopoietic cell transplantation (HCT) for hematologic malignancies experience hyperglycemic events during treatment, leading to adverse outcomes. Understanding how hyperglycemia during the acute HCT treatment phase impacts outcomes is vital for preventing and mitigating adverse events. This integrative review evaluates the impact of hyperglycemia on adult patients undergoing HCT.Literature Search: PubMed, MEDLINE®, and CINAHL® electronic databases were used to identify relevant articles.Data Evaluation: The final sample for this integrative review included 12 empirical quantitative reports of clinical patient outcomes. Of the 12, 10 are retrospective, 1 is case-control, and 1 is prospective.Data Analysis: Content analysis was used to synthesize and summarize findings.Presentation of Findings: A review of published literature found associations between hyperglycemia and infection, time to engraftment, development of acute graft-versus-host disease, length of stay, and overall survival. Patient-related risk factors for hyperglycemia included older age, preexisting diabetes, and insulin resistance (i.e., prediabetes). Patients of normal weight experiencing hyperglycemia had worse outcomes than patients who were overweight or obese. Treatment-related risk factors for hyperglycemia include dose and duration of immunosuppressants, specifically corticosteroids, treatment with antihyperglycemic medications, and use of total parenteral nutrition.Implications for Nursing Practice: HCT is one of the most complex treatments for hematologic disorders. The transplantation nurse, as part of an interdisciplinary team, plays an essential role in glycemic control during the acute phase of HCT. Understanding the effects of hyperglycemia, as well as factors that place the patient at risk for hyperglycemia, allows the nurse to make well-informed, proactive interventions aimed at glycemic control.Oncology nursing forum 09/2014; 41(5):E302-E312. DOI:10.1188/14.ONF.E302-E312 · 2.83 Impact Factor