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Mesenchymal stem cells (MSCs) are found in a variety of tissues, including human bone marrow; secrete hematopoietic cytokines; support hematopoietic progenitors in vitro; and possess potent immunosuppressive properties. We hypothesized that cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs) from HLA-identical sibling donors after myeloablative therapy could facilitate engraftment and lessen graft-versus-host disease (GVHD); however, the safety and feasibility of this approach needed to be established. In an open-label, multicenter trial, we coadministered culture-expanded MSCs with HLA-identical sibling-matched HSCs in hematologic malignancy patients. Patients received either bone marrow or peripheral blood stem cells as the HSC source. Patients received 1 of 4 study-specified transplant conditioning regimens and methotrexate (days 1, 3, and 6) and cyclosporine as GVHD prophylaxis. On day 0, patients were given culture-expanded MSCs intravenously (1.0-5.0 x 10(6)/kg) 4 hours before infusion of either bone marrow or peripheral blood stem cells. Forty-six patients (median age, 44.5 years; range, 19-61 years) received MSCs and HLA-matched sibling allografts. MSC infusions were well tolerated, without any infusion-related adverse events. The median times to neutrophil (absolute neutrophil count > or = 0.500 x 10(9)/L) and platelet (platelet count > or = 20 x 10(9)/L) engraftment were 14.0 days (range, 11.0-26.0 days) and 20 days (range, 15.0-36.0 days), respectively. Grade II to IV acute GVHD was observed in 13 (28%) of 46 patients. Chronic GVHD was observed in 22 (61%) of 36 patients who survived at least 90 days; it was extensive in 8 patients. Eleven patients (24%) experienced relapse at a median time to progression of 213.5 days (range, 14-688 days). The probability of patients attaining disease- or progression-free survival at 2 years after MSC infusion was 53%. Cotransplantation of HLA-identical sibling culture-expanded MSCs with an HLA-identical sibling HSC transplant is feasible and seems to be safe, without immediate infusional or late MSC-associated toxicities. The optimal MSC dose and frequency of administration to prevent or treat GVHD during allogeneic HSC transplantation should be evaluated further in phase II clinical trials.

The objective of this study was to examine the association between body mass index (BMI) and the incidence of pulmonary complications (PCs) after hematopoietic stem cell transplant (HCT). We reviewed 398 adult patients with non-Hodgkin lymphoma (NHL) who received autologous or allogeneic HCT between 1993 and 1997. BMI was classified as normal (18.5 < BMI ≤ 24.9), overweight (24.9 < BMI ≤ 30) and obese (BMI > 30). Multivariate logistic regression was used to analyze the relationship between BMI and presence of PCs within 100 days post-HCT while adjusting for patient-, disease- and transplant-related variables. The incidence of PCs within 100 days post-HCT was 32% (n= 129). Median BMI was 25.4 (range: 18.6–52.2). Median age was 48.8 years (range: 19.5–73.6 years). Multivariate analysis failed to show significant association between BMI and PCs. However, a total body irradiation (TBI)-based conditioning regimen was associated with lower rate of PCs. [ABSTRACT FROM AUTHOR]

Studies suggest that patients who live in rural areas may have worse clinical outcomes compared with patients living in urban areas. We studied whether place of residence (rural versus urban) is associated with clinical outcomes of patients with leukemia or myelodysplastic syndrome (MDS) who received an unrelated donor hematopoietic cell transplantation (HCT). Patients'' residential ZIP code at the time of transplant was used to determine rural or urban designation based on the Rural Urban Commuting Codes. The study included 6140 patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 121 U.S. HCT centers: 1179 (19%) came from rural areas, whereas 4961 (81%) came from urban areas. Rural and urban patients were similar in patient-, disease-, and transplant-related characteristics aside from household income and distance traveled to the HCT center. After adjusting for income and other significant patient, disease, and transplant-related variables, the risk of overall mortality between patients residing in rural and urban areas were not statistically significant (relative risk 1.01, 95% confidence intervals 0.93-1.10, P = .74). Similar outcomes were noted for treatment-related mortality (TRM), disease-free survival (DFS), and relapse. Patient''s income, derived from the U.S. Census and based on their residential ZIP code, was independently associated with outcomes. In summary, our study showed no differences in the clinical outcomes of patients from rural or urban areas after unrelated donor HCT. [Copyright &y& Elsevier]

Abstract: Outcome disparity associated with race or ethnicity in the United States has been observed in hematopoietic cell transplantation (HCT). The underlying reasons for such disparity are not known. In the United States, an optimal study of health care disparity by race or ethnicity involves consideration of both biologic and psychosocial determinants, which requires an adequately powered, prospective cohort study design. To better characterize the nature and quantify the magnitude of the many impediments relevant to conducting a successful prospective study involving racial or ethnic minorities in HCT, we conducted a feasibility study to help guide planning of a larger scale outcome and disparity study in HCT. The primary questions to be addressed in the study were: (1) can we establish a racially or ethnically diverse patient sample that will respond to a survey focused on sociodemographic, economic, health insurance, cultural, spiritual, and religious well-being, and social support information? (2) What is the retention rate in the study over time? (3) What is the quality of the data collected from the patients over time? The challenges we faced in conducting this multicenter feasibility study are summarized in this report. Despite the difficulty in conducting disparity studies in racial and ethnic minorities, such studies are essential to ensure that people of all ethnic and racial backgrounds have the best chance possible of benefiting from HCT. [Copyright &y& Elsevier]

Abstract: Hematopoietic stem cell transplantation (HSCT) as a field of medicine has been subject to rapid development and evolution since its inception. Traditionally, HSCT has been used for therapy of a diverse group of malignancies, bone marrow failure states, and inherited disorders. The rapid evolution of transplantation technology coupled with the diverse outcomes associated with a heterogeneous group of patients has stymied the development of consensus over objective programmatic indicators of quality, especially as they pertain to outcomes. In some regard, the lack of consensus has caused transplant programs to respond to a more consumer-driven paradigm of evaluation. The community of providers of transplantation therapies has responded by establishing standards for accreditation of facilities and uniform presentation of programmatic data. Rapid acceptance of the need for meaningful quality programs to address all aspects of the transplant facility has moved HSCT to the forefront of implementing standards for medical practice. Because definition of optimal outcomes in HSCT is likely to remain elusive, it is imperative that providers involved with HSCT continue to take a leadership role in defining program quality through further research. [Copyright &y& Elsevier]

An introduction is presented in which the editor discusses various articles within the issue on topics including risk factors associated with deaths from hematopoietic stem cell transplantation (HSCT), a case-control analysis on HSCT patients, and relapse of the HSCT.

Abstract: To compare the clinical outcomes of older (age ≥55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged ≥55 years to 1949 NHL patients <55 years during the years 1990–2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended. [Copyright &y& Elsevier]

We evaluated whether or not a patient''s area of primary residence is an independent risk factor for overall survival (OS) after HLA-identical sibling or autologous hematopoietic stem cell transplantation (HSCT). This retrospective cohort study included patients who underwent autologous (n = 1739) or HLA-identical sibling (n = 267) HSCT to treat a hematologic malignancy between 1983 and 2004 at the University of Nebraska Medical Center. Primary area of residence, using the patient''s zip code, was categorized as either urban or rural (including isolated, small rural, or large rural) according to the Rural Urban Commuting Area Codes (RUCA) classification system. An association between area of primary residence and survival was examined using Cox proportional hazards regression analysis while adjusting for patient-, disease-, and treatment-related variables. Patients from rural areas who received autologous HSCT had a higher relative risk of death (relative risk = 1.18; P = .016) than urban patients who underwent the same procedure. Survival rates in patients from rural and urban locations are as follows: 1 year, 73% vs 78% (P = .04); 5 year, 48% vs 54% (P = .012). We failed to detect a significant difference in the risk of death according to primary area of residence in the HLA-identical sibling HSCT cohort, although this may be from lack of statistical power. Our findings suggest that the primary location of a patient''s residence may be an independent risk factor for survival after HSCT. [Copyright &y& Elsevier]

Abstract: Racial or ethnic minorities with leukemia who receive HLA-identical sibling hematopoietic stem cell transplants (HSCTs) are reported to have worse survival when compared with whites. Characteristics of US HSCT centers according to the proportion of ethnic minorities who undergo transplantation were compared to explore systematic differences among centers; the association with 100-day mortality was evaluated to determine whether center factors may explain the observed discrepant survival among ethnic minorities. One hundred sixteen US transplantation centers that performed HLA-identical sibling transplantations for leukemia were analyzed. We compared physician and health care provider staffing, transplantation unit procedure and resources, and medical center organization according to the volume procedure ratio of ethnic minorities who underwent transplantation and also according to the ratio of Hispanics who underwent transplantation. Centers that performed transplantation in a higher proportion of ethnic minorities were more likely to perform fewer transplantations per year, to have fewer devoted transplant beds, to be in an urban setting, to have a lower physician to patient volume ratio, and to follow up survivors 1 year after transplantation. Centers that performed transplantation in a higher proportion of Hispanics were more likely to perform fewer transplantations per year and to have fewer devoted transplantation beds, were less likely to perform outpatient transplantations, were more likely to be in an urban setting, and were less likely to have posttransplantation immunization protocols. Observed differences in center factors were not associated with 100-day mortality after adjustment for disease severity. Our results suggest that the inferior survival reported in ethnic minorities after HSCT may not be readily explained by center effects. [Copyright &y& Elsevier]