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The New England Journal of Medicine Jun 2023In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.
METHODS
In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the , , , and loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause.
RESULTS
In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups.
CONCLUSIONS
Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).
Topics: Adult; Humans; Bronchiolitis Obliterans Syndrome; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Methotrexate; Mycophenolic Acid; Neoplasm Recurrence, Local; Tacrolimus; Unrelated Donors; Hematologic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37342922
DOI: 10.1056/NEJMoa2215943 -
Clinical Research in Cardiology :... Feb 2024Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has... (Review)
Review
Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has not been diagnosed and, consequently, patients have not been treated of their pulmonary disease. Recognizing and treating COPD in patients with CVDs is important because optimal treatment of the COPD carries important benefits on cardiovascular outcomes. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual report that serves as a clinical guideline for the diagnosis and management of COPD around the world and has very recently released the 2023 annual report. Here, we provide a summary of the GOLD 2023 recommendations that highlights those aspects of more interest for practicing cardiologists dealing with patients with CVD who may suffer COPD.
Topics: Humans; Cardiologists; Pulmonary Disease, Chronic Obstructive; Lung
PubMed: 37233751
DOI: 10.1007/s00392-023-02217-0