TABLE 5.
Reported associations of pharmacokinetic parameters of alemtuzumab and clinical outcomes.
| First author, year | n | Age, median (range) | Diagnosis | Regimen | Dose alemtuzumab | Major findings |
|---|---|---|---|---|---|---|
| Marsh et al. (2016) | 105 | 4.7 (0.3–27.2) | HLH: 54 (51%) | FluMel | Distal dosing | Peritransplant alemtuzumab levels have impact on the incidence of aGvHD, mixed chimerism and lymphocyte recovery. 18% developed GvHD with alemtuzumab levels ≥0.16 μg/ml, 68% in patients with levels ≤0.15 μg/ml. Mixed chimerism occurred in 21% of the patients with ≤0.15 μg/ml, in 42% with levels between 0.16 and 4.35 μg/ml and in 100% if levels were above 4.35 μg/ml. Patients with levels ≥0.57 μg/ml had lower T-cell counts at day 100. A therapeutic range at day 0 of 0.2–0.4 μg/ml is recommended. |
| BMF: 13 (12%) | 3/10/15/20 mg over days -22 to −19 | |||||
| (S)CID: 17 (17%) | <10 kg: 3/10/10/10 mg | |||||
| CGD: 5 (5%) | Intermediate dosing | |||||
| Metabolic: 4 (4%) | 1 mg/kg over days -14 to −10 | |||||
| SCD: 2 (2%) | Proximal dosing | |||||
| Other: 10 (10%) | 3/10/15/20 mg or 1 mg/kg starting at day -12 or closer to HSCT | |||||
| Bhoopalan et al. (2020) | 13 | 15.5 (3–21) | ALL: 8 (61.5%) | FluThioMelRitux | Subcutaneous n = 8 | BSA-based dosing of alemtuzumab is feasible in pediatric haplo-transplantation patients. AUC of alemtuzumab did not have a significant relation with OS, engraftment, IR and GvHD. |
| AML: 3 (23.1%) | Subcutaneous and intravenous n = 5 | |||||
| CML: 1 (7.7%) | Test dose of 2 mg/m2 plus total dose of 45 mg/m2 | |||||
| Therapy-related MDS: 1 (7.7%) | Dose given from days -14 to -11 | |||||
| Dong et al. (2021) | 29 | 6.4 (0.28–21.4) | HLH: 13 (45%) | FluMel | Subcutaneous | Proposed therapeutic range of 0.15–0.6 μg/ml on the day of transplantation is associated with better HSCT outcomes (less aGVHD and improved lymphocyte recovery). To achieve this optimal level allometric or BSA-based dosing is advised. Top-up dose on day -3 for patients who, based on individualized PK estimation, will have a concentration <0.15 μg/ml on the day of transplantation is recommended. |
| CGD: 2 (7%) | 0.5–0.6 mg/kg | |||||
| IPEX: 2 (7%) | 1 mg/kg | |||||
| SAA: 5 (17%) | Dose given days -14 to −10 or -14 – -12 | |||||
| (S)CID: 3 (10%) | Top-up dose was given either on day -3 or -1 | |||||
| Other: 4 (14%) |
HLH, hemophagocytic lymphohistiocytosis; (S)CID, (severe) combined immune deficiency; CGD, chronic granulomatous disease; SCD, sickle cell disease; IPEX, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; SAA, severe aplastic anemia; Ritux, rituximab.