Pharmacokinetics of Alemtuzumab in Pediatric Patients Undergoing T-Cell Depleted Haploidentical Hematopoietic Cell Transplantation (HCT)

Introduction Haploidentical HCT is a viable option for patients with hematological malignancies who do not have a matched donor available. However, the presence of HLA-mismatch can be associated with increased risk of donor graft rejection, graft versus host disease (GVHD), infections due to delayed immune reconstitution and regimen-related toxicity. Methods We used alemtuzumab, a monoclonal antibody targeting CD52, for in vivo depletion of host and donor T cells - as CD52 is predominantly expressed in T cells. Recipients also received donor grafts that underwent ex vivo T-cell depletion (immunomagnetic depletion of CD3+ cells). The objective of this study is to study the pharmacokinetics of alemtuzumab in pediatric patients with hematological malignancies undergoing T-cell depleted haploidentical HCT, and to identify factors that might be associated with differences in drug exposure. Alemtuzumab was administered as described in Table 1, and levels were checked at days -10, -8, -3, and weeks 1, 2, 4, 8 and 16 from serum samples of 13 patients. A compartmental pharmacokinetic model was fit to the data using nonlinear mixed-effects modeling. Results Out of the thirteen patients, twelve engrafted neutrophils at a median of day +11 and platelets at a median of day +15. Seven patients were alive one year after transplant. Our cohort included one primary and one secondary graft failure, three relapses and six patients who had grade II-IV acute GVHD. In addition, seven patients experienced mixed chimerism, and required donor lymphocyte infusion (DLI) for correction. The median (range) clearance (ml/day/m2) and area under the curve (AUC) (µg*day/mL) were 255 (211, 600) and 117.1 (28.1, 165.4), respectively. The median serum level on day –3 was 3.8 µg/mL. 77% of the patients had detectable levels as late as week 4 and the median (range) half-life was 11 days (4.3, 12.9). Clearance increased with age, weight, and serum creatinine (p Conclusion While our study is limited by small sample size, to our knowledge this is the first pharmacokinetic study of alemtuzumab in pediatric haploidentical transplant patients using a body surface area dosing strategy.