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Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21-58) and the median doses of eculizumab was three (IQR;2-5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95-555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future., (© 2023. The Author(s).)

An 18-year-old male patient who had been diagnosed with chronic granulomatous disease at 2 years old and suffering from repeated severe infections underwent human leukocyte antigen haploidentical bone marrow transplantation from his mother using reduced intensity conditioning. After engraftment, donor lymphocyte infusion was initiated to decrease donor chimerism on day 96. On day 120, acute graft-versus-host disease occurred; hence, steroid administration was initiated. On day 173, a generalized convulsion occurred; multiple abscesses were observed in the brain, lung, kidney, and prostate. Aspergillus siamensis of unknown pathogenic status was cultured in the abscess fluid from the brain, prostate, and kidney; accordingly, he was diagnosed with disseminated aspergillosis involving the brain, prostate, lungs, and kidney. Despite using a combination of various antifungal drugs, he died of multiple organ failure on day 239. Disseminated aspergillosis following the hematopoietic stem cell transplantation is a fatal complication. If infection symptoms are observed, the presence of any fungal antigens should be examined. Appropriate samples should be promptly collected, and adequate antifungal drugs should be administered based on the fungal species and drug sensitivity results.

Severe congenital neutropenia (SCN) is characterized by chronic neutropenia with recurrent infections from early infancy and a predisposition to myelodysplastic syndrome/acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with SCN who develop myelodysplastic syndrome/AML. We report an 8-year-old girl with SCN carrying an ELANE mutation that had been refractory to granulocyte colony-stimulating factor. The patient experienced recurrent infections and then developed AML. The counts of leukemic blasts that harbored both CSF3R and RUNX1 mutations spontaneously decreased with antimicrobial therapy, leading to partial remission. After AML recurrence, HSCT was successfully performed using modified chemotherapy and a conditioning regimen. Serial donor lymphocyte infusions against mixed chimerism induced complete donor chimerism over 4 years without any infections or AML relapse. This case suggests the importance of carefully managing neutropenia-related infections, leukemia progression, and HSCT in patients with SCN developing AML. [ABSTRACT FROM AUTHOR]