Influence of Timing PTCy in AlloSCT

Allogenic Haematopoetic Transplantation, Cyclophosphamide Toxicity

haemorrhagic cystitis, cyclophosphamide, allogenic haematopoetic transplantation

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.

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. 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. The usual protocol for the administration of cyclophosphamide (PTCy) after transplantation states that it should be started at least 72 hours (days +3 and +4) after the infusion of haematopoietic progenitors, but this interval can be extended to 84 hours (days +3.5) and the days of administration have been changed to days +3 and +5 with optimal results. In some patients, the infusion of haematopoietic precursors is carried out in the afternoon because of the need for nursing care. This meant that cyclophosphamide had to be administered in the evening, 72 hours after the infusion of the precursors. After review of the recommendations to reduce the risk of haemorrhagic cystitis, it was recommended that cyclophosphamide infusion be delayed in the morning on days +4 and +5, although in reality, taking into account the hours since haematopoietic progenitor infusion, these would be days +3.5 and +4.5 instead of days +3 and +4 in the afternoon/evening. This change means a 12-hour delay in the start of cyclophosphamide. Therefore, the investigators refer to day +3.5 from the infusion of haematopoietic progenitors.

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