A sequential addition of silyl cyanide and ketene silyl acetals to esters was achieved by a gallium trihalide catalyst to produce β-cyano-β-siloxy esters. This is the first example of the sequential addition of two different carbon nucleophiles to esters. The employment of lactones provided α,α-disubstituted cyclic ethers with a cyano group and an ester moiety.
View Article and Find Full Text PDFThe National Institutes of Health global score for chronic graft-versus-host disease was devised by experts but was not based on empirical data. We hypothesized that analysis of prospectively collected data would enable derivation of a more accurate model for estimating mortality risk. We analyzed 574 adult patients with chronic graft-versus-host disease enrolled in a multicenter, observational study, using multivariate time-varying analysis accounting for serial changes in severity of involvement of eight individual organ sites over time.
View Article and Find Full Text PDFCurr Phys Med Rehabil Rep
December 2013
Although the goal of dysphagia rehabilitation is the same, population needs, clinical practice patterns, availability of resources, and dysphagia research varies greatly around the world. The goal of this review is to introduce the reader to the context in which dysphagia rehabilitation is practiced, to describe practice patterns, and to highlight the dysphagia research being performed in three distinct regions of the world: North America, New Zealand and Australia, and Japan.
View Article and Find Full Text PDFAllogeneic hematopoietic cell transplantation (HCT) can cure some chronic lymphocytic leukemia (CLL) subjects. This study compared outcomes of myeloablative (MA) and reduced-intensity conditioning (RIC) transplants from HLA-matched sibling donors (MSD) for CLL. From 1995 to 2007, information regarding 297 CLL subjects was reported to the Center of International Blood and Marrow Transplant Research; of these, 163 underwent MA and 134 underwent RIC MSD HCT.
View Article and Find Full Text PDFThis study was designed to characterize failure-free survival (FFS) as a novel end point for clinical trials of chronic graft-versus-host disease (GVHD). The study cohort included 400 consecutive patients who received initial systemic treatment of chronic GVHD at our center. FFS was defined by the absence of second-line treatment, nonrelapse mortality, and recurrent malignancy during initial treatment.
View Article and Find Full Text PDFBiol Blood Marrow Transplant
September 2014
Although older patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) may experience higher morbidity, the impact of chronic graft-versus-host disease (GVHD) on quality of life (QOL) and survival outcomes for older compared with younger patients is currently unknown. We utilized data of patients with moderate or severe chronic GVHD (N = 522, 1661 follow-up visits, a total of 2183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. We examined the relationship between age group (adolescent and young adult, "AYA," 18 to 40 years; "middle-aged," 41 to 59 years; and "older," ≥ 60 years) and QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]), physical functioning (Human Activity Profile [HAP]), functional status (2-minute walk test [2MWT]), nonrelapse mortality, and overall survival.
View Article and Find Full Text PDFObjective: To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results.
Methods: In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions.
Background: Langerhans cells (LCs) are self-renewing epidermal myeloid cells that can migrate and mature into dendritic cells. Recipient LCs that survive cytotoxic therapy given in preparation for allogeneic hematopoietic cell transplantation may prime donor T cells to mediate cutaneous graft-versus-host disease (GVHD). This possible association, however, has not been investigated in the setting of nonmyeloablative allografting.
View Article and Find Full Text PDFThe 2005 National Institutes of Health (NIH) consensus criteria for chronic GVHD have set standards for reporting. Many questions, however, have arisen regarding their implementation and utilization. To identify perceived areas of controversy, we conducted an international survey on diagnosis and scoring of chronic GVHD.
View Article and Find Full Text PDFAn allogeneic hematopoietic cell transplantation from an HLA-identical donor after high-dose (myeloablative) pretransplantation conditioning is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized that total body irradiation (TBI) conditioning regimens may be associated with better outcomes than those without TBI. To answer this, we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (n = 126) or not (n = 54), who received transplants from an HLA-identical sibling donor between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research.
View Article and Find Full Text PDFThe 2005 National Institutes of Health (NIH) Consensus Conference recommended assessment of lung function in patients with chronic graft-versus-host disease (GVHD) by both pulmonary function tests (PFTs) and assessment of pulmonary symptoms. We tested whether pulmonary measures were associated with nonrelapse mortality (NRM), overall survival (OS), and patient-reported outcomes (PRO). Clinician and patient-reported data were collected serially in a prospective, multicenter, observational study.
View Article and Find Full Text PDFPurpose: To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT).
Patients And Methods: HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192).
Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness are lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human leukocyte antigen-matched sibling or from an unrelated donor during the years 2000 to 2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy.
View Article and Find Full Text PDFWe evaluated short-term response endpoints for acute graft-versus-host disease treatment trials. We postulated that response endpoints should correlate with reduced symptom burden and decreased subsequent treatment failure, defined as non-relapse mortality, recurrent malignancy, or additional systemic treatment. The cohort included 303 consecutive patients who received initial systemic steroid treatment for acute graft-versus-host disease.
View Article and Find Full Text PDFResearch on muscle activation patterns during swallowing has been limited. Newly developed 320-row area detector computed tomography (320-ADCT) has excellent spatial and temporal resolution, which facilitates identification of laryngopharyngeal structures and quantitative kinematic analysis of pharyngeal swallowing. We investigated muscle activity patterns by observing the changes in length of hyoid muscles.
View Article and Find Full Text PDFThe indium triiodide catalyzed single-stage cascade reaction of N-sulfonyl amides with hydrosilanes and two types of organosilicon nucleophiles such as silyl cyanide and silyl enolates selectively promoted deoxygenative functionalization to give α-cyanoamines and β-aminocarbonyl compounds, respectively.
View Article and Find Full Text PDFChronic GVHD (cGVHD) is associated with mortality, disability and impaired quality of life. Understanding the role of comorbidity in patients with cGVHD is important both for prognostication and potentially for tailoring treatments based on mortality risks. In a prospective cohort study of patients with cGVHD (n=239), we examined the performance of two comorbidity scales, the Functional Comorbidity Index (FCI) and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI).
View Article and Find Full Text PDFAn efficient method for the synthesis of fused heteroaromatic dihydrosiloles via Ni-catalyzed hydrosilylation/intramolecular Ir-catalyzed dehydrogenative coupling of the Si-H bond with the heteroaromatic C-H bond has been developed. The method is efficient for both electron-deficient and -rich heterocycles. It exhibits high functional group tolerance and good regioselectivity.
View Article and Find Full Text PDFSclerotic chronic graft-versus-host disease (GVHD) can result in disability after allogeneic hematopoietic cell transplantation. We assessed the incidence and risk factors of sclerosis and its association with transplant outcomes among 977 consecutive patients treated with systemic immunosuppression for chronic GVHD. Sclerosis was defined when cutaneous sclerosis, fasciitis, or joint contracture was first documented in the medical record.
View Article and Find Full Text PDFHand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as elements of chronic graft-versus-host disease (GVHD) assessment in clinical trials. Using all available data (n = 584 enrollment visits, 1689 follow-up visits, total of 2273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life instruments and Human Activity Profile [HAP]), chronic GVHD global severity (National Institutes of Health global score, clinician global score, and patient-reported global score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival, nonrelapse mortality, and failure-free survival) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all P < .
View Article and Find Full Text PDFThe impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients.
View Article and Find Full Text PDFAlthough data support adverse prognosis of overlap subtype of chronic grant-versus-host disease (GVHD), the importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Using data from the Chronic GVHD Consortium observational cohort study (N = 567, total of 2115 visits), we examined whether the site of GI (esophageal, upper GI, or lower GI) and type of hepatic (bilirubin, alkaline phosphatase, alanine aminotransferase) involvement are associated with overall survival (OS) and nonrelapse mortality (NRM), symptoms, quality of life (QOL) and functional status measures. In multivariate analysis utilizing data from enrollment visits only, lower GI involvement (HR, 1.
View Article and Find Full Text PDFBone Marrow Transplant
August 2013
Oral chronic GVHD (cGVHD) is a serious complication of alloSCT. Scales and instruments to measure oral cGVHD activity and severity have not been prospectively validated. The objective of this study was to describe the characteristics of oral cGVHD and determine the measures most sensitive to change.
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