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.