Characterization of the Use and Efficacy of Isavuconazonium Sulfate in a Pediatric Oncology and Stem Cell Transplant Population: A Single Institution Retrospective Review.

Isavuconazonium sulfate (ISA) is a triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis in adults. This single-center, retrospective review of pediatric oncology and stem cell transplant patients receiving ISA for prophylaxis (n=20) or treatment (n=6) of invasive fungal disease (IFD) aims to characterize real-world clinical efficacy and toxicity of ISA in patients <18 years of age. Of 20 patients receiving ISA for prophylaxis, three patients had presumed breakthrough IFD (1 proven, 2 probable/possible). No adverse effects were attributed to ISA use or led to the discontinuation of therapy.

T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML.

The only curative approach for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) arising in patients with Fanconi anemia (FA) is allogeneic hematopoietic stem cell transplantation (HCT); however, HCT approaches are inconsistent and limited data on outcomes exist. We retrospectively evaluated outcomes of thirty patients with FA and MDS/AML who underwent first allogeneic HCT with a T-cell depleted (TCD) graft at our institution. Patients were transplanted on successive protocols with stepwise changes in cytoreduction and GVHD prophylaxis. All but two patients (93%) experienced durable hematopoietic engraftment. With median follow-up of 8.7 years, 5-year OS was 66.8% and DFS 53.8%. No significant differences in survival were found in patients with high-risk prognostic features (age ≥20 years, AML diagnosis, alternative donor graft) or when stratified by conditioning regimen. The 5-year cumulative incidences of relapse and NRM were 24.3% and 21.9%, respectively. NRM was higher in patients ≥20 years at HCT but did not otherwise differ. We herein demonstrate promising outcomes following allogeneic HCT for patients with FA and MDS/AML using TCD grafts, particularly in a cohort of high-risk patients with 50% ≥20 years and a majority receiving mismatched grafts. Future prospective studies are needed to compare this approach with other HCT platforms.

Association between busulfan exposure and survival in patients undergoing a CD34+ selected stem cell transplantation.

Busulfan is an alkylating drug routinely used in conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). A myeloablative conditioning regimen, including busulfan, is commonly used in patients undergoing T-cell depletion (TCD) and allo-HCT, but data on optimal busulfan pharmacokinetic (PK) exposure in this setting are limited. Between 2012 and 2019, busulfan PK was performed to target an area under the curve exposure between 55 and 66 mg × h/L over 3 days using a noncompartmental analysis model. We retrospectively re-estimated busulfan exposure following the published population PK (popPK) model (2021) and correlated it with outcomes. To define optimal exposure, univariable models were performed with P splines, wherein hazard ratio (HR) plots were drawn, and thresholds were found graphically as the points at which the confidence interval crossed 1. Cox proportional hazard and competing risk models were used for analyses. 176 patients were included, with a median age of 59 years (range, 2-71). Using the popPK model, the median cumulative busulfan exposure was 63.4 mg × h/L (range, 46.3-90.7). The optimal threshold was at the upper limit of the lowest quartile (59.5 mg × h/L). 5-year overall survival (OS) with busulfan exposure ≥59.5 vs <59.5 mg × h/L was 67% (95% CI, 59-76) vs 40% (95% CI, 53-68), respectively (P = .02), and this association remained in a multivariate analyses (HR, 0.5; 95% CI, 0.29; 0.88; P = .02). In patients undergoing TCD allo-HCT, busulfan exposure is significantly associated with OS. The use of a published popPK model to optimize exposure may significantly improve the OS.

Letermovir for Cytomegalovirus Prevention in Adolescent Patients Following Hematopoietic Cell Transplantation.

There are limited data for letermovir as primary cytomegalovirus (CMV) prophylaxis in patients less than 18 years of age. We report 9 adolescent patients who received letermovir following hematopoietic cell transplantation. No patients developed clinically significant CMV while taking letermovir. Letermovir was well tolerated and efficacious in preventing CMV infections.