Which medications are used in the treatment of pediatric acute lymphoblastic leukemia (ALL)?

Updated: Jan 03, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Jennifer Reikes Willert, MD  more...
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Answer

Drugs commonly used during remission induction therapy include dexamethasone or prednisone, vincristine, asparaginase, and daunorubicin. Consolidation therapy often includes methotrexate (MTX) and 6-mercaptopurine (6-MP) or cyclophosphamide and cytarabine. Drugs used for intensification include cytarabine, cyclophosphamide, etoposide, dexamethasone, asparaginase, doxorubicin, MTX, 6-MP, and vincristine. Continuation therapy is based on oral 6-MP and MTX with pulses of vincristine and glucocorticoid (prednisone or dexamethasone). Intrathecal chemotherapy includes primarily MTX, which may also be combined with hydrocortisone and cytarabine (“triple-intrathecal therapy”). Imatinib and dasatinib are also approved for children with newly diagnosed with Ph+ ALL. [39, 11, 58]

It is important to note that corticosteroids can adversely suppress the function of the hypothalamic-pituitary-adrenal (HPA) axis and such suppression can have adverse effects on a patient's ability to respond to different stresses, such as severe infection. A Cochrane Database review of 7 studies showed adrenal insufficiency occurred in nearly all ALL patients in the first days after cessation of glucocorticoid therapy. Although the majority of patients recovered within a few weeks, a small number of patients had adrenal insufficiency lasting up to 34 weeks. [39]

Tyrosine kinase inhibitors (TKIs) have emerged as treatment options for patients with the B-cell ALL subtype known as Philadelphia chromosome-like ALL (Ph-like ALL). According to a genomic profiling study of 1725 children, adolescents, and young adults with B-precursor ALL, investigators found that 15% of these patients had Ph-like ALL and that within this subgroup, 91% exhibited kinase-activating gene changes. The investigators also reported that, based on in vitro testing, leukemia cells expressing ABL1, ABL2, CSF1R, and PDGFRB gene fusion were sensitive to the TKI dasatinib, while EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and leukemia cells expressing ETV6 -NTRK3 fusion were sensitive to crizotinib. [40, 41, 58, 59]

Drug therapies for relapsed or refractory ALL include cell-based gene therapy (eg, tisagenlecleucel) [36] and reinduction regimens.


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