TABLE 3.
Reported associations of pharmacokinetic parameters of fludarabine and clinical outcomes.
| First author, year | n | Age, median (range) | Diagnosis | Regimen | Dose | Major findings |
|---|---|---|---|---|---|---|
| Ivaturi et al. (2017) | 133 | 5.0 (0.2–17.9) | Hem. malig: 59 (44%) | BuFlu: 40 (30%) | 3–5 x 40 mg/m2: 55 (41%) | No association with Flu and TRM (p = 0.35). In the malignancy group DFS was highest at 1 year post HSCT in patients with a cumulative AUC >15 mg*h/L compared to <15 mg*h/L (82.6 vs. 52.8%, p = 0.04). A cumulative AUC of >15 mg*h/L is considered as a minimum exposure threshold. |
| IEI: 18 (14%) | FluCy: 45 (34%) | 3–5 x 12.5–35 mg/m2: 40 (30%) | ||||
| HBP: 8 (6%) | BuFluClo: 18 (14%) | 3–5 x 0.9–1.22 mg/m2: 38 (29%) | ||||
| Metabolic: 22 (16%) | FluThioMel: 15 (11%) | |||||
| BMF: 22 (16%) | Other: 15 (11%) | |||||
| Epidermolysis bullosa: 4 (4%) | ||||||
| Mohanan et al. (2017) | 53 (no. of children not specified) | 17 (3–57) | AA: 40 (75%) | FluCy: 29 (55%) | 6 × 30 mg/m2 | AUC >29.4 µM*h was a significant factor associated with aGVHD in multivariate analysis (p = 0.02) |
| FA: 13 (25%) | FluCyTBI: 20 (38%) | None of the PK parameters showed any association with engraftment, mixed chimerism, rejection, overall survival or TRM. | ||||
| FluCyATG: 4 (7%) | ||||||
| Chung et al. (2018) | 43 | 11.8 (1.3–18.5) | Acute leukemia: 29 (67.4%) | BuFluVP16: 24 (55.8%) | 6 × 40 mg/m2: 40 (93%) | No significant association was found between AUC and toxicities, GvHD, relapse and survival. |
| Other malig: 2 (4.7%) | BluFlu: 12 (27.9%) | 5 × 40 mg/m2: 3 (7%) | ||||
| Non-malignant: 12 (28%) | BuFluMel: 4 (9.3%) | |||||
| FluCy: 2 (4.7%) | ||||||
| BuFluCy: 1 (2.3%) | ||||||
| Langenhorst et al. (2019) | 192 (119 adults, 73 children | 36.2 (0.23–74) | Benign: 68 (35%) | BuFlu | 4 × 40 mg/m2 | Flu exposure is a predictor for EFS. NRM was increased with high Flu exposure (p < 0.001) and more graft failure was seen with low exposure (p = 0.04). An optimal cumulative AUC of 20 mg*h/L (±5) is suggested. The optimal exposure group had a significantly higher EFS compared with the above-optimal exposure group (HR 2.0; 95%CI 1.1–3.5, p = 0.01) and (non-significantly) higher than the below-optimal group (HR 1.8; 95%CI 0.72–4.5, p = 0.21). |
| Leukemia/lymphoma: 71 (37%) | ||||||
| MDS: 30 (16%) | ||||||
| Plasma cell disorder: 23 (12%) |
AA, aplastic anemia; FA, fanconi anemia; TBI, total body irradiation.