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The Lancet鲜有干细胞的文章+ L+ r1 @4 Y2 E" n& t3 s
现在贴出2011年The Lancet Infectious Diseases有关干细胞的两篇文章* I% X7 H# I* z) M6 ]5 j; K
1.The Lancet Infectious Diseases, Early Online Publication, 16 March 2 W4 p6 F7 X7 U( q& `
Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial
" H2 l- H3 A- L) c3 p2 R5 v0 }Dr Francisco M Marty MD a , Prof Per Ljungman MD b, Genovefa A Papanicolaou MD c, Drew J Winston MD d, Roy F Chemaly MD e, Lynne Strasfeld MD f, Jo-Anne H Young MD g, Tulio Rodriguez MD h, Prof Johan Maertens MD i, Michael Schmitt MD j, Prof Hermann Einsele MD k, Augustin Ferrant MD l, Jeffrey H Lipton MD m, Stephen A Villano MD n, Hongzi Chen PhD n, Prof Michael Boeckh MD o, for the Maribavir 1263—300 Clinical Study Group‡6 r- U# m8 Z/ d" f: u4 x' }' G
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Background
% r, P! ?* b) z: G5 DAvailable drugs against cytomegalovirus have adverse effects that compromise their prophylactic use in recipients of allogeneic stem-cell transplants. We assessed the safety, tolerability, and antiviral activity of oral maribavir in such patients.
* {& h) y3 C. X9 R Y/ Z) UMethods
1 Q: K; y; p2 ]* e1 m, O1 L& q. xIn this placebo-controlled, randomised, double-blind, multicentre phase 3 study, we enrolled adult patients recipient-seropositive or donor-seropositive for cytomegalovirus who had undergone allogeneic stem-cell transplantation. Patients were recruited from 90 centres in Canada, Europe, and the USA. After engraftment, patients were stratified by recipient cytomegalovirus serostatus and conditioning regimen (myeloablative or reduced-intensity) and assigned (2:1) by masked computer-generated randomisation sequence to receive maribavir 100 mg twice daily or placebo for up to 12 weeks, with weekly blood cytomegalovirus surveillance. If the virus was detected, administration of study drug was stopped and pre-emptive anticytomegalovirus treatment started. The primary endpoint was cytomegalovirus disease within 6 months of transplantation. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT00411645.7 v( N' f" R7 k# l4 O
Findings
r9 i" f& ?! q: v7 R1 Y* K* K0 cBetween December, 2006, and May, 2008, 681 patients were enrolled and assigned to receive maribavir (454) or placebo (227). The incidence of cytomegalovirus disease within 6 months was 20 of 454 (4%) for the maribavir group and 11 of 227 (5%) for the placebo group (OR 0·90; 95% CI 0·42—1·92). During the 100 days following transplantation, cytomegalovirus infection rates as measured by pp65 antigenaemia were lower in the maribavir group (26·4%) than in the placebo group (34·8%; OR 0·67; 0·47—0·95), but not when measured by plasma cytomegalovirus DNA PCR (27·8% vs 30·4%; OR 0·88; 0·62—1·25), nor by initiation of treatment against cytomegalovirus (30·6% vs 37·4%; OR 0·73, 0·52—1·03). Maribavir was well tolerated: most adverse events, including incident acute graft-versus-host disease and neutropenia, affected both groups equally, except for taste disturbance (15% maribavir, 6% placebo).
, k9 ^1 [+ p+ }1 O- m5 UInterpretation3 Z$ \4 b! x- V, q$ b& ]! y
Compared with placebo, maribavir prophylaxis did not prevent cytomegalovirus disease when started after engraftment. Cytomegalovirus disease as a primary endpoint might not be sufficient to show improvements in cytomegalovirus prevention in recipients of allogeneic stem-cell transplants in the setting of pre-emptive antiviral treatment. Clinical and virological composite endpoints should be used in future trials.1 M4 P h4 c7 ^5 |2 G7 \+ u
# A! W( Z5 Y* L' C7 w% A! j2.The Lancet Infectious Diseases, Volume 11, Issue 4, Pages 255 - 257, April 2011 Q6 g, `+ l3 N5 L" {8 Q
Why did maribavir fail in stem-cell transplants?+ H: G+ c0 T$ q9 ~
Original TextDavid R Snydman a
! Y# K" r4 j6 k/ W) cIn this issue of The Lancet Infectious Diseases , Francisco Marty and colleagues 1 report a very important but negative study. The study was a multicentre, multinational, randomised, placebo-controlled, double-blind, phase 3 trial to establish the efficacy of maribavir in prevention of cytomegalovirus infection and disease in recipients of stem-cell transplantation. The trial failed to show superiority of prophylaxis with maribavir compared with placebo (with subsequent pre-emptive therapy with valg ... |
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发表于 2011-6-25 18:23
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发表于 2011-6-25 21:50
