Evaluation of the Influence of Timing of Post-transplant Cyclophosphamide in Allogeneic Haematopoietic Stem Cell Transplant Patients.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- incidence haemorrhagic cystitis Grade II-IV
研究概览
简要总结
Cyclophosphamide, administered after the infusion of haematopoietic progenitor cells, is used to prevent graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allogeneic HSCT) and has been shown to reduce the incidence of GVHD.
Cyclophosphamide can cause haemorrhagic cystitis as a result of the direct toxicity of its metabolite acrolein to the bladder mucosa or urothelium upon accumulation in the urine. Hyperhydration and the administration of mesna, which forms a non-urotoxic compound with acrolein, are among the most commonly used strategies to prevent this. The administration of cyclophosphamide in the morning is also recommended.
The protocol for post-transplant cyclophosphamide states that it should be started at least 72 hours (days +3 and +4) after haematopoietic progenitor infusion, but this interval can be extended to 84 hours (day +3.5). After reviewing the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended to delay the infusion of cyclophosphamide to the early morning of days +4 and +5, although in reality, taking into account the hours since the infusion of haematopoietic progenitors, it would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change will mean a delay of 12 hours in the start of cyclophosphamide, so the investigators will refer to day +3.5 from the infusion of the haematopoietic precursors.
详细描述
Cyclophosphamide administered after haematopoietic stem cell infusion is used for the prevention of graft-versus-recipient disease (GVHD) in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-SCT) and has been shown to reduce the incidence of GVHD.
However, cyclophosphamide can cause haemorrhagic cystitis (HC) as one of the best known adverse effects. This is due to the direct toxicity of the cyclophosphamide metabolite, acrolein, to the bladder mucosa or urothelium as it accumulates in the urine. The incidence of HC can vary from 10 to 70% of patients and increases the number of days spent in hospital as well as morbidity and mortality after transplantation. Among the most common risk factors and causative agents, in addition to cyclophosphamide, are BK polyomavirus infections, with cyclophosphamide-induced HC often occurring within 72 hours of the administration of cyclophosphamide.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
In order to ensure proper hydration, to promote diuresis during the day and to reduce the time that acrolein is in contact with the mucosa, the administration of cyclophosphamide in the morning is recommended.
There are several strategies to prevent cyclophosphamide-induced HC, such as hyperhydration with saline and forcing diuresis with furosemide, alkalinisation of diuresis or administration of mesna, which forms a non-urotoxic complex with acrolein in the urinary tract and prevents tissue damage. However, further studies are needed to understand the best strategy to prevent HC, especially in the setting of allo-SCT.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult recipients (>18 years old) of Allo-SCT
- •Allo SCT between January 1, 2014 and December 31, 2022
- •PTCy dose 50 mg/kg x 2 days
排除标准
- •Patients with no record of time of administration of PTCy
- •PTCy dose of 30 mg/kg x 2 days
研究组 & 干预措施
Non Cystitis hemorrhagic
Non cystitis hemorrhagic or grade I
干预措施: Cyclophosphamide (Drug)
Cystitis hemorrhagic
Cystitis hemorrhagic grade II-III
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
incidence haemorrhagic cystitis Grade II-IV
时间窗: 6 months
To compare the incidence of grade II to IV haemorrhagic cystitis, according to the CTCAE classification, depending on the schedule of post-transplant cyclophosphamide administration in consecutive patients.
次要结局
- Mortality and relapsed(6 months)
- GVHD acute and chronic(6 months)