Infectious complications in children conditioned for allogeneic haematopoietic stem cell transplantation with reduced intensity conditioning or with treosulfan-based reduced toxicity preparative regimen

Abstract

Background

To expand access to allogeneic haematopoietic stem cell transplantation (allo-HSCT) to patients who are ineligible for conventional myeloablative FTBI- or busulfan-based preparative regimens, the idea of reduced intensity conditioning (RIC) in the early 1990s, and somewhat later in the late 1990s the idea of treosulfan-based reduced toxicity conditioning, were created. However, there is still need for further optimization of the conditioning regimen for allo – HSCT, which should demonstrate sufficient myeloablative, immunosuppressive and antitumour effects (in the case of malignant disease) along with low early and late transplant-related mortality.

Aim

Comparison of infections occurring in children prepared for allogeneic HSCT with reduced intensity conditioning (RIC) and treosulfan-based reduced toxicity conditioning regimen (TREO-RTC).

Material/Methods

Data concerning infections in patients conditioned for allogeneic-HSCT with RIC and reported in references found using the PubMed database were compared with data concerning 51 children prepared for allogeneic HSCT with TREO-RTC and reported by Grund et al. (2006).

Results

Following RIC-HSCT the majority of infections occurred beyond day +30. Bacteria are leading agents causing infections. The pattern and incidence of fungal infections are comparable to those observed after myeloablative conditioning, whilst incidence of EBV-reactivation and EBV-related disease is increased, but BK-viruria is less common. Reported 1-year mortality related to infections after RIC-HSCT is around 10%. In 51 children conditioned with TREO-RTC the profile, incidence and timing of infections were comparable to those observed after conventional regimens (Grund et al., 2006). Three (5.9%) of them died due to infectious complications, one (1.9%) before day +100, and 2 (3.9%) late after transplantation in the course of extensive chronic GvHD.

Conclusions

Infections remain an issue in children undergoing allogeneic HSCT after RIC or TREO-RTC. Therefore prophylaxis, surveillance, early diagnosis and pre-emptive treatment of infections still play an important role in supportive care after RIC- and TREO-RTC-HSCT. This approach should be adjusted to the immune reconstitution profile related to immunosuppressive intensity of the regimen and GvHD prophylaxis, donor type, donor/recipient pretranspant viral status, stem cell source and GVHD occurrence. Standardization of supportive care after RIC- and TREO-RTC-HSCT, related to factors which determine risk of infections, is needed.