Drug-resistance Profile in Multiple-relapsed Childhood Acute Lymphoblastic Leukemia

Aim: To analyze the drug-resistance profile at first and subsequent relapse in children with acute lymphoblastic leukemia (ALL). Patients and Methods: A total of 154 pediatric ALL samples were tested for ex vivo chemosensitivity for up to 19 drugs. Their combined drug resistance profile (PVA score) was analyzed. Results: The median relative resistance scores between patients with multiple relapse and those with first relapse considering all drugs was 2.0. The median PVA score at subsequent relapses was 8 vs. 6 at first relapse (p=0.004). Samples from multiple-relapsed ALL were more drug resistant to: prednisolone (>1.9-fold), dexamethasone (>1.5-fold), vincristine (3.1-fold), L-asparaginase (5-fold), mitoxantrone (2.4-fold), cytarabine (4.3-fold), mercaptopurine (2.2-fold), thioguanine (4.8-fold), etoposide (2.6-fold) and melphalan (2.7-fold). Lymphoblasts at multiple relapse were comparably resistant to: daunorubicin, doxorubicin, cyclophosphamide, ifosfamide, busulfan, treosulfan, fludarabine, clofarabine and bortezomib. Conclusion: In comparison to first relapse, subsequent relapsed childhood ALL is more ex vivo-resistant to most tested drugs.