Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
JAMA ; 322(13): 1261-1270, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31573637

ABSTRACT

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.


Subject(s)
Ascorbic Acid/administration & dosage , Multiple Organ Failure/prevention & control , Respiratory Distress Syndrome/drug therapy , Sepsis/drug therapy , Vitamins/administration & dosage , Adult , Aged , Ascorbic Acid/therapeutic use , Biomarkers/blood , C-Reactive Protein/analysis , Double-Blind Method , Female , Humans , Infusions, Intravenous , Intensive Care Units , Male , Middle Aged , Multiple Organ Failure/etiology , Organ Dysfunction Scores , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/mortality , Sepsis/complications , Sepsis/mortality , Thrombomodulin/blood , Vitamins/therapeutic use
2.
Biol Blood Marrow Transplant ; 18(6): 874-80, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22040844

ABSTRACT

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR](Adj) = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Lymphoid/therapy , Leukemia, Myeloid/therapy , Transplantation Conditioning , Adolescent , Adult , Aged , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Humans , Length of Stay/statistics & numerical data , Leukemia, Lymphoid/immunology , Leukemia, Lymphoid/mortality , Leukemia, Myeloid/immunology , Leukemia, Myeloid/mortality , Male , Middle Aged , Patient Discharge , Patient Readmission/statistics & numerical data , Quality of Health Care , Recurrence , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Whole-Body Irradiation
3.
Leuk Lymphoma ; 52(6): 986-93, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21314484

ABSTRACT

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34+ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34+ cells mobilized (p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cells/drug effects , Lymphoma, Mantle-Cell/therapy , Peripheral Blood Stem Cell Transplantation/methods , Adult , Aged , Antigens, CD34/blood , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells/metabolism , Humans , Leukapheresis/methods , Lymphoma, Mantle-Cell/blood , Male , Methotrexate/administration & dosage , Middle Aged , Retrospective Studies , Time Factors , Transplantation, Autologous , Treatment Outcome , Vincristine/administration & dosage
4.
Br J Haematol ; 152(5): 561-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21223255

ABSTRACT

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P<0·001], as did those who were relapsed or refractory (HR 4·9, P<0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Epidemiologic Methods , Female , Hematopoietic Stem Cell Mobilization/methods , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prognosis , Recurrence , Treatment Outcome , United States/epidemiology , Young Adult
5.
Leuk Lymphoma ; 51(9): 1699-704, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20629524

ABSTRACT

Patients with acute myeloid leukemia (AML) with intermediate or high risk cytogenetics are often considered for allogeneic hematopoietic stem cell transplant (AHSCT) in first remission. Between attainment of remission and AHSCT, post-remission chemotherapy is frequently administered, though there is no evidence for its effectiveness. This study was performed to determine the impact of post-remission chemotherapy on outcome after AHSCT. A subset analysis was performed to determine whether the influence of post-remission chemotherapy might be different in those with intermediate compared to high risk cytogenetics. There was no significant difference in relapse mortality (RM) (p = 0.70), non-relapse mortality (NRM) (p = 0.12), or survival (OS) (p = 0.15) between post-remission chemotherapy groups. There was no difference in RM, NRM, or OS between cytogenetic groups according to whether they received post-remission chemotherapy. No differential effect between intermediate and high risk cytogenetics was detected (RM, p = 0.80; NRM, p = 0.23; OS, p = 0.26). These data do not show a benefit of post-remission chemotherapy before AHSCT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm, Residual/drug therapy , Adolescent , Adult , Cohort Studies , Cytarabine/administration & dosage , Cytogenetic Analysis , Daunorubicin/administration & dosage , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Graft vs Host Disease/therapy , Humans , Idarubicin/administration & dosage , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm, Residual/genetics , Neoplasm, Residual/mortality , Remission Induction , Retrospective Studies , Survival Rate , Transplantation, Homologous , Treatment Outcome , Young Adult
6.
Biol Blood Marrow Transplant ; 16(12): 1738-46, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20558313

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. To identify patient, disease, and treatment characteristics associated with outcome, we analyzed prognostic factors in 98 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥18 years, first SCT either autologous or allogeneic, and second SCT allogeneic. Patients whose second transplant was myeloablative (MA) had shorter survival (median 3.2 versus 14.7 months, P < .001) than patients whose second transplant was nonmyeloablative (NMA). In multivariable analysis, MA second transplant was associated with a higher risk of NRM (hazard ratio [HR] 2.01, P = 0.022) and death (HR 2.13, P = 0.002). Improved survival after NMA second transplant occurred primarily in patients without acute leukemia and when the first transplant was allogeneic. Among 17 patients transplanted within 3 months of first transplant, mortality was 100% and median survival was 2.3 months. MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM. NMA second transplants were associated with substantially less NRM and despite a higher incidence of relapse, significantly improved survival compared to MA second transplants.


Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Adolescent , Adult , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia/mortality , Leukemia/surgery , Male , Middle Aged , Multivariate Analysis , Prognosis , Recurrence , Reoperation , Retrospective Studies , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Homologous , Treatment Outcome , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...