Cornely Oliver A, Leguay Thibaut, Maertens Johan, Vehreschild Maria J G T, Anagnostopoulos Achilles, Castagnola Carlo, Verga Luisa, Rieger Christina, Kondakci Mustafa, Härter Georg, Duarte Rafael F, Allione Bernardino, Cordonnier Catherine, Heussel Claus Peter, Morrissey C Orla, Agrawal Samir G, Donnelly J Peter, Bresnik Mark, Hawkins Michael J, Garner Will, Gökbuget Nicola
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Department I of Internal Medicine, Clinical Trials Centre Cologne (ZKS), Center for Integrated Oncology (CIO KölnBonn), German Centre for Infection Research (DZIF), partner site Bonn-Cologne, University of Cologne, Cologne, Germany.
Service d'hématologie clinique et Thérapie cellulaire, Hôpital du Haut-Lévèque, CHU de Bordeaux, France.
J Antimicrob Chemother. 2017 Aug 1;72(8):2359-2367. doi: 10.1093/jac/dkx133.
To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).
In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB.
Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB ( n = 237) or placebo ( n = 118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group ( P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group ( P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo ( P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB.
The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.
预防新诊断的急性淋巴细胞白血病（ALL）成人患者在缓解诱导化疗期间发生侵袭性真菌病（IFD）。
在一项双盲多中心3期研究中，患者在缓解诱导治疗期间按2:1随机分配，接受5mg/kg静脉注射的预防性脂质体两性霉素B（L-AMB）或安慰剂，每周两次。主要终点是确诊或疑似IFD的发生情况。次要终点包括关注预防性L-AMB的安全性和耐受性的指标。
来自欧洲和南美洲86个中心的355例患者接受了至少一剂L-AMB（n = 237）或安慰剂（n = 118）。独立评估的确诊和疑似IFD发生率在L-AMB组为7.9%（18/228），在安慰剂组为11.7%（13/111）（P = 0.24）。可能的IFD发生率在L-AMB组为4.8%（11/228），在安慰剂组为5.4%（6/111）（P = 0.82）。两组的缓解诱导期中位数均为22天。两组的总体死亡率相似：L-AMB组为7.2%（17/237），安慰剂组为6.8%（8/118）（P = 1.00）。L-AMB组低钾血症和肌酐升高明显更常见。
新诊断ALL的成人患者在缓解诱导化疗期间，安慰剂组的IFD发生率为11.7%，接受L-AMB的患者中IFD发生率无显著差异，这表明所研究的L-AMB方案作为预防IFD无效。IFD发生率似乎高于先前报道，值得进一步研究。L-AMB的耐受性符合预期。需要进一步研究以确定ALL缓解诱导化疗期间的最佳抗真菌策略。
