A Case of Dasatinib-Induced Nephrotic Syndrome in a Child with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Tyrosine kinase inhibitors (TKI) were developed as the targeted therapy of cancer and are considered an important treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leuke-mia (ALL). 1,2 As the use of TKIs has increased, its side effects have also been reported. A few cases of children who developed nephrotic syndrome following treatment of TKI, have been reported. 3 A 5-year-old boy was diagnosed with Ph+ ALL with petechi-ae on both lower legs. He achieved remission through induction chemotherapy including daunorubicin, vincristine, L-as-paraginase, and prednisolone and started taking imatinib, the first generation of TKIs (300 mg), after ascertaining BCR-ABL rearrangement. After 2 years, he had developed central nervous system (CNS) relapse of ALL during maintenance che-motherapy. Therefore, reinduction chemotherapy was started on Pediatric Oncology Group 9412 protocol and imatinib was replaced with dasatinib. He achieved remission after chemo-therapy and was prepared for hematopoietic stem cell trans-plantation (HSCT). Twenty-six days after HSCT, he had as-ymptomatic proteinuria. Urinalysis showed 4+ proteinuria without other symptoms. Urine total protein for 24 hrs was 5636 mg, 234 mg/m 2 /hr and spot urine protein-creatinine ratio was 15.24, meeting the diagnostic requirements for ne-phrotic syndrome. Proteinuria was sustained even after stopping dasatinib for 5 days. Therefore, kidney biopsy was performed for diagnosis. Light microscopically, glomeruli had no cellular proliferation or capillary wall thickening (Fig. 1A). Tubulointerstitium did not show abnormal pathology either. Electron microscopically, most foot processes were fused, but no electron dense deposits were present (Fig. 1B). Immuno-fluorescent study revealed no positive results for anti IgG, A, M, C3, and C1q. Within 1 week of stopping dasatinib, urinaly-sis showed no proteinuria and urine total protein for 24 hrs was 395 mg, which was in the nephrotic range of nephrotic syndrome. Since then, post-HSCT course was uneventful until five months after HSCT, when he developed hepatic graft-versus host disease and expired. To the best of our knowledge, this is the first reported pediat-ric case of dasatinib induced nephrotic syndrome in Korea. Ruebner, et al. 3 described 4 cases with pediatric malignancy with TKI-induced nephrotic syndrome. As in our case, resolution of nephrotic syndrome was achieved in three of the four cases after discontinuation of TKI therapy. According to the report of the Pone di Legno childhood ALL consortium, the outcome of Ph+ ALL before the imatinib era, was very poor, with a 7-year event-free survival (EFS) rate of 25% and an …