Pediatric Acute Lymphoblastic Leukemia Medication

Updated: Jul 22, 2022
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK); Chief Editor: Jennifer Reikes Willert, MD  more...
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Medication Summary

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. Methotrexate is administered during interim maintenance at a high dose with leucovorin rescue, or at a much lower dose increased sequentially (Capizzi methotrexate). The former is more effective for high-risk B-ALL, the latter for standard-risk B-ALL and for T-ALL. [38, 45] 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 is MTX, which can be combined with hydrocortisone and cytarabine (“triple-intrathecal therapy” or TIT), but the recently concluded COG AALL1131 trial showed no benefit for TIT over intrathecal MTX in children with high-risk B-ALL. [3] Imatinib and dasatinib are also approved for children with newly diagnosed Ph+ ALL. [12, 46, 47]

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. [46]

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. [47, 48, 49, 50]

Drug therapies for relapsed or refractory ALL include cell-based gene therapy (eg, tisagenlecleucel) [42] and reinduction regimens.


Antineoplastic Agents

Class Summary

Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2), then finally a mitotic cell division (ie, phase M).

Cell-division rates vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may be decreased in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones and is the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents act at specific phases of the cell cycle, whereas others (ie, alkylating agents, anthracyclines, cisplatin) are not phase-specific. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.

Vincristine (Vincasar PFS)

Vincristine is a chemotherapeutic agent derived from the periwinkle plant. This agent acts by inhibiting microtubule formation in mitotic spindles, causing metaphase arrest.

Daunorubicin (Cerubidine)

Daunorubicin is an anthracycline that intercalates with DNA and interferes with DNA synthesis.

Methotrexate (Trexall)

Methotrexate is a folate analogue that competitively inhibits dihydrofolate reductase, thus inhibiting DNA, RNA, and protein synthesis.

Mercaptopurine (Purinethol)

Mercaptopurine is a synthetic purine analogue that kills cells by incorporating into DNA as a false base.


Cytarabine is a synthetic analogue of nucleoside deoxycytidine. This agent undergoes phosphorylation to arabinofuranosyl-cytarabine-triphosphate (ara-CTP), a competitive inhibitor of DNA polymerase.

Etoposide (Toposar)

Etoposide inhibits topoisomerase II and breaks DNA strands, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle.


Cyclophosphamide is chemically related to the nitrogen mustards. When this drug is used as an alkylating agent, the mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

Nelarabine (Arranon)

Nelarabine is a prodrug of 9-beta-D-arabinofuranosylguanine (ara-G). This agent is converted to the active arabinofuranosyl-guanine-5'-triphosphate (ara-GTP), a T-cell–selective nucleoside analogue. Leukemic blast cells accumulate ara-GTP, which allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death.

Nelarabine was approved by the US Food and Drug Administration [FDA] as an orphan drug to treat T-cell lymphoblastic lymphoma (a type of non-Hodgkin lymphoma [NHL]) that does not respond or that relapses with at least 2 chemotherapy regimens.

Clofarabine (Clolar)

Clofarabine is a purine nucleoside antimetabolite that inhibits DNA synthesis and is indicated for relapsed or refractory acute lymphoblastic leukemia in pediatric patients. Pools of cellular deoxynucleotide triphosphate are decreased by inhibiting ribonucleotide reductase and terminating DNA chain elongation and repair. This agent also disrupts mitochondrial membrane integrity.



Class Summary

Immunomodulators (eg, interleukin 6 [IL-6] inhibitors) may be needed for therapies resulting in cytokine release.

Tocilizumab (Actemra)

Interleukin-6 receptor antagonist. Decreases C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate, and amyloid A. It is indicated for treatment of cytokine release syndrome (CRS) resulting from tisagenlecleucel therapy. Clinical signs of CRS correlate with T-cell activation and high levels of cytokines, including interleukin 6 (IL-6).


Enzymes, Oncology

Class Summary

Asparaginase is an enzyme that catalyzes conversion of the amino acid L-asparagine into aspartic acid and ammonia. Pharmacological effect is based on the killing of leukemic cells owing to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival. 

Asparaginase Erwinia chrysanthemi (Erwinaze)

Contains an asparagine specific enzyme derived from Erwinia chrysanthemi. Indicated as part of a multiagent chemotherapeutic regimen as a substitute for asparaginase (Elspar), which was discontinued by the manufacturer in August 2012. 

Asparaginase Erwinia chrysanthemi recombinant (Rylaze)

Recombinant-derived asparaginase product. Indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E coli–derived asparaginase. 

Pegaspargase (Oncaspar)

Conjugate of monomethoxypolyethylene glycol (mPEG) and E coli–derived L-asparaginase. It is indicated as a component of a multi-agent chemotherapeutic regimen for the first line treatment of ALL. It is also indicated for use in patients with hypersensitivity to native forms of L-asparaginase. Pegylation of the molecule prolongs the duration of action to 2-3 weeks. 

Calaspargase pegol (Asparlas)

Asparagine specific enzyme derived from Escherichia coli, as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. It is indicated as part of a multiagent chemotherapeutic regimen for ALL in pediatric and young adult patients aged 1 month to 21 years. This product provides a longer interval between doses and an extended shelf-life compared with other asparaginase products. 


Antineoplastics, Tyrosine Kinase Inhibitor

Class Summary

When added to chemotherapy, tyrosine kinase inhibitors (TKIs) have been shown to improve progression-free survival in newly diagnosed patients with Ph+ ALL. [47, 50]

Imatinib (Gleevec)

Imatinib is a selective BCR-ABL tyrosine kinase inhibitor. It is indicated for newly diagnosed children aged 1 y or older with Ph+ ALL in combination with chemotherapy.

Dasatinib (Sprycel)

Second generation TKI indicated for newly diagnosed children aged 1 y or older with Philadelphia chromosome positive (Ph+) ALL in combination with chemotherapy. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones.


CAR T-Cell Therapies

Class Summary

In chimeric antigen receptor (CAR) T-cell therapy, autologous T-cells are collected from peripheral blood and genetically engineered to express a CAR that targets a specific molecule on cancer cells. The modified T-cells are then expanded and reinfused into the patient, after lymphodepletion with conditioning chemotherapy.

Tisagenlecleucel (Kymriah)

CD19-directed genetically modified autologous T-cell immunotherapy indicated for patients aged 25 years or younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.


Antineoplastic agents, Anti-CD19/CD3

Blinatumomab (Blincyto)

Bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T-cells by connecting CD3 in the T-cell receptor complex with CD19 on benign and malignant B cells. It is indicated for treatment of Ph- relapsed or refractory B-cell precursor ALL. It was also granted accelerated approval for the treatment of CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥ 0.1% in adults and children.



Class Summary

Prophylactic antimicrobial drugs are given to prevent infection in patients receiving chemotherapy.

Sulfamethoxazole and trimethoprim (Septra, Bactrim)

Sulfamethoxazole and trimethoprim inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. All immunocompromised patients can be given cotrimoxazole to prevent Pneumocystis carinii pneumonia (PCP).


Immunocompromised patients who do not tolerate cotrimoxazole due to myelosuppression may receive IV pentamidine to prevent Pneumocystis carinii pneumonia (PCP).



Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body’s immune response to diverse stimuli. These agents are significantly toxic to lymphoblasts, and two thirds of patients with pediatric ALL who receive steroid therapy alone go into remission.


Prednisone is a corticosteroid and an important chemotherapeutic agent in the treatment of acute lymphoblastic leukemia (ALL). This agent is used in induction therapy and is also given as intermittent pulses during continuation therapy.

Dexamethasone (Baycadron, Maxidex, Ozurdex)

Dexamethasone is another corticosteroid that acts as an important chemotherapeutic agent in the treatment of ALL. Like prednisone, this agent is used in induction and reinduction therapy and is also given as intermittent pulses during continuation therapy.



Class Summary

These agents may change the permeability of the fungal cell, resulting in a fungicidal effect.


Fluconazole may be used in patients at high risk (eg, infant ALL) to prevent fungal infections. It is a synthetic triazole that inhibits fungal cell growth by inhibiting CYP-dependent synthesis of ergosterol, a vital component of fungal cell membranes.