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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Hematology

      Acute Lymphoblastic Leukemia (ALL) Medication

      Updated: Jul 02, 2021
      • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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      Medication

      Medication Summary

      Antineoplastic agents are used for induction, consolidation, and maintenance therapy and central nervous system (CNS) prophylaxis in patients with acute lymphoblastic leukemia (ALL). Those medications cause severe bone marrow depression, and only physicians specifically trained in their use should administer them. In addition, access to appropriate supportive care is required. Other drug classes used in treatment of ALL include the following:

      • Corticosteroids may be used during induction, consolidation, and/or maintenance therapy
      • Tyrosine kinase inhibitors are used in treatment of Philadelphia chromosome–positive (Ph+) ALL
      • Drug therapies for relapsed or refractory ALL include cell-based gene therapy and reinduction regimens
      • Colony-stimulating factors are used to treat or prevent neutropenia and to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation (BMT) and in management of chronic neutropenia        
      • Prophylactic antibiotics and antifungal drugs are given to prevent infection in patients receiving chemotherapy
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      Corticosteroids

      Class Summary

      Corticosteroids may be used during induction, consolidation, and/or maintenance therapy for acute lymphoblastic leukemia (ALL).

      Prednisone (Deltasone, Rayos)

      Prednisone is a corticosteroid that has a wide range of activities. In ALL, this agent is used because of its direct antileukemic effects.

      Dexamethasone (DexPak, LoCort, ZonaCort)

      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.

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      Antineoplastics

      Class Summary

      Antineoplastic agents are used for induction, consolidation, maintenance, and central nervous system (CNS) prophylaxis.

      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 vinca alkaloid agent that acts by arresting cells in metaphase.

      Vincristine liposomal (Marqibo)

      A sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine. Indicated for treatment of Ph-negative ALL for patients in second or greater relapse or whose disease has progressed following 2 or more antileukemia therapies.

      Methotrexate (Trexall, Xatmep, Otrexup, Rasuvo)

      Methotrexate is an antimetabolite of the folic acid analogue type. This agent inhibits dihydrofolate reductase, resulting in inhibition of DNA synthesis, repair, and cellular replication.

      Mercaptopurine (Purinethol)

      Mercaptopurine is antimetabolite of the purine analogue type. Its primary effect is inhibition of DNA synthesis.

      Cyclophosphamide

      Cyclophosphamide is an alkylating agent of the nitrogen mustard type that acts by inhibiting cell growth and proliferation.

      Cytarabine

      Cytosine arabinoside is an antimetabolite that induces activity as a result of activation to cytarabine triphosphate and includes inhibition of DNA polymerase and incorporation into DNA and RNA.

      Daunorubicin (Cerubidine)

      Daunorubicin is an anthracycline that inhibits topoisomerase II. This agent also inhibits DNA and RNA synthesis by intercalating between DNA base pairs.

      Idarubicin (Idamycin)

      Idarubicin is a topoisomerase II inhibitor that inhibits cell proliferation by inhibiting DNA and RNA polymerase.

      Mitoxantrone (Novantrone)

      Mitoxantrone is also a topoisomerase II inhibitor. This agent inhibits cell proliferation by intercalating DNA and inhibiting topoisomerase II.

      Nelarabine (Arranon)

      Nelarabine is a prodrug of the deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (ara-G) that is converted to the active 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.

      This agent is approved by the US Food and Drug Administration (FDA) as an orphan drug to treat persons with T-cell ALL whose disease has not responded to or which has relapsed 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. It is indicated for the treatment of patients aged 1-21 years who have relapsed or refractory acute ALL. For adults older than 21 years, base dosing on surface area as in pediatrics. Clofarabine is not indicated for adults older than 21 years.

      Inotuzumab (Besponsa)

      Inotuzumab is a CD22-directed antibody-drug conjugate (ADC) indicated for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Recognizes human CD22. The small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic agent which covalently attaches to antibody via a linker. Data suggest anticancer activity of inotuzumab ozogamicin is due to binding of ADC to CD22-expressing tumor cells, followed by internalization of ADC-CD22 complex, and ultimately activating N-acetyl-gamma-calicheamicin 19 dimethylhydrazide, which induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death.

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      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 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.

      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. 

      Calaspargase pegol (Asparlasl)

      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.

      Pegaspargase (Oncaspar)

      Conjugate of monomethoxypolyethylene glycol (mPEG) and E coli–derived L-asparaginase. It is indicated as a component of a multiagent 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. 

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      Tyrosine Kinase Inhibitors

      Class Summary

      Philadelphia chromosome-positive (Ph+) ALL is treated with tyrosine kinase inhibitors. These agents provide targeted therapy by inhibiting the BCR-ABL fusion protein.

      Imatinib (Gleevec)

      Imatinib is indicated for relapsed or refractory Ph+ ALL. It is also indicated for newly diagnosed PH+ CML in chronic phase and for Ph+ CML in blast crisis, accelerated phase, or chronic phase after failure of interferon-alpha therapy.

      Nilotinib (Tasigna)

      Nilotinib is indicated for newly diagnosed Ph+ CML in chronic phase and for the treatment of Ph+ CML (chronic phase, accelerated phase) in patients resistant or intolerant to prior therapy including imatinib.

      Dasatinib (Sprycel)

      Dasatinib is indicated for Ph+ ALL with resistance or intolerance to prior therapy. It is also indicated for newly diagnosed Ph+ CML in chronic phase, CML (chronic, accelerated, or plast phase Ph+) with resistance or intolerance to prior therapy including imatinib.

      Ponatinib (Iclusig)

      Ponatinib is a kinase inhibitor indicated for patients with CML or Ph+ ALL that is resistant or intolerant to prior tyrosine kinase inhibitor therapy, including those with the T315I mutation. Because ponatinib has a high risk for thromboembolic events, its use is restricted for patients whom no other TKI therapy is indicated.

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      Antineoplastic agents, Anti-CD19/CD3

      Class Summary

      Bispecific T cell engager antibodies are a type of immunotherapy that assist’s the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage 2 different targets simultaneously, thereby juxtaposing T cells to cancer cells, thereby helping place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger apoptosis.

      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 (TCR) 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.

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      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.

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      Antimicrobials

      Class Summary

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

      Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS)

      Trimethoprim-sulfamethoxazole (TMP-SMZ) inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. All immunocompromised patients should be treated with TMP-SMZ to prevent Pneumocystis carinii pneumonia (PCP).

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      Immunomodulators

      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).

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      Colony-Stimulating Factors

      Class Summary

      Colony-stimulating factors (CSF) act as hematopoietic growth factors that stimulate the development of granulocytes. These agents are used to treat or prevent neutropenia when patients receive myelosuppressive cancer chemotherapy and to reduce the period of neutropenia that is associated with bone marrow transplantation (BMT). Colony-stimulating factors are also used to mobilize autologous peripheral blood progenitor cells for BMT and in management of chronic neutropenia.

      Filgrastim (Neupogen, Granix, Zarxio)

      Filgrastim is a granulocyte colony-stimulating factor (G-CSF) that activates and stimulates the production, maturation, migration, and cytotoxicity of neutrophils.

      Pegfilgrastim (Neulasta, Neulasta Onpro)

      Pegfilgrastim is a long-acting filgrastim created by the covalent conjugate of recombinant G-CSF (ie, filgrastim) and monomethoxypolyethylene glycol. As with filgrastim, this agent acts on hematopoietic cells by binding to specific cell surface receptors, thereby activating and stimulating production, maturation, migration, and cytotoxicity of neutrophils.

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      Antifungals

      Class Summary

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

      Nystatin (Bio-Statin)

      Nystatin is used to prevent fungal infections in mucositis. This agent is a fungicidal and fungistatic antibiotic from Streptomyces noursei that is effective against various yeasts and yeastlike fungi. Nystatin acts by changing the permeability of the fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.

      Treatment with this agent should continue until 48 hours after the symptoms disappear. Nystatin is not substantially absorbed from the gastrointestinal tract.

      Clotrimazole

      Clotrimazole may be used instead of nystatin to prevent fungal infections. It is a broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells.

      Itraconazole (Onmel; Sporanox; Sporanox Pulsepak)

      Itraconazole has fungistatic activity and is used to prevent fungal infections in high-risk patients. This drug is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-dependent synthesis of ergosterol, a vital component of fungal cell membranes. The bioavailability of this drug is greater in the oral solution compared with the capsule formulation.

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