Search

Background: Anti‐thymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis is widely used for mismatched unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Although recent literature suggested improved outcomes with PTCy‐based regimens when compared to ATG‐based regimens these studies used doses of ATG ≥5 mg/kg. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower‐dose ATG‐based regimens at our center. Methods: We retrospectively analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG‐based regimens for all adults undergoing allogeneic HCT at The Ottawa Hospital from 2015 to 2022. Data regarding demographics, conditioning regimen, dose of ATG, rates of GVHD, duration of remission, and survival, were collected and analyzed. Results: Seventy‐seven (n = 77) patients (males 62.3%; median age 50 years) underwent allogeneic HCT from MMUD. Majority(81%; n = 63) received 2.5 mg/kg of rabbit ATG and remaining 18.2% (n = 14) received 4.5 mg/kg. Grade II‐IV acute GVHD occurred in 24.7% (n = 19) while any chronic GVHD occurred in 32.5% (n = 25) patients. After a median follow‐up of 21 months, relapse occurred in 28.6% of patients. Two‐year OS, GRFS, CIR, and NRM were 60.6%, 45.3%, 16.9%, and 18.2% respectively. Dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses. Conclusions: When compared to published studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG may potentially lead to improved outcomes in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy‐based regimens to determine ideal GVHD prophylaxis for these patients. [ABSTRACT FROM AUTHOR]

Summary: In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol‐conjugated E. coli L‐asparaginase (PEG‐EcASNase) 1000 iu/m2 was administered intramuscularly with risk‐stratified treatment. In induction, patients received two PEG‐EcASNase doses, 14 days apart. Post‐induction, non‐high‐risk patients (Regimens A, B) received 1–2 doses in delayed intensification (DI) while high‐risk Regimen C patients received 6–10 PEG‐EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase‐related toxicity and ASNase‐associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144–307 iu/l), 265 iu/l (165–401 iu/l) and 292 iu/l (194–386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient −9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG‐EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Dose adjustments of Day 11 Methotrexate (MTx) for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation (HCT) are common due to mucositis, renal injury, or other reasons. The impact of omitting or adjusting doses of MTx in the era of ATG‐based GVHD prophylaxis remains unexplored.We retrospectively analyzed the outcomes of all adult patients undergoing allogeneic HCT who received ATG‐based GVHD prophylaxis at The Ottawa Hospital from January 2019 to December 2022. We compared outcomes of patients having only Day 11 MTx dose reductions due to mucositis(MTxRD group) with patients receiving full dose MTx on all 4 days (MTxFD group). The impact of Day 11 MTx dose reduction on outcomes were assessed using Kaplan–Meier analyses and log rank test.Three hundred and four patients (median age 58 [17–74] years; 64% male) underwent allogeneic HCT during the study period. Baseline characteristics were similar between the MTxRD group (n = 69) and MTxFD group (n = 199) except for an increased proportion of MAC regimens in MTxRD group. The incidence of severe aGVHD (7.2% vs. 7.5%; p = 0.96) and chronic GVHD (15.9% vs. 15.6%; p = 0.89) were not different between the two groups. The 2‐year OS (59% vs. 69.8%; p = 0.11), GRFS (42.4% vs. 47.6%; p = 0.32), NRM (17.7% vs. 12.2%; p = 0.45) or relapse/progression (CIR 27.4 vs. 26.6%; p = 0.55) were also similar between the two groups.In patients receiving ATG‐based GVHD prophylaxis regimens, there were similar GVHD and survival outcomes in patients who received no or reduced D11 MTx when compared to full dose MTx. Dose adjustments of D11 MTx due to mucositis appear to be safe in the era of ATG‐based GVHD prophylaxis regimens. [ABSTRACT FROM AUTHOR]