What is the role of cellular therapy in the treatment of pediatric acute lymphoblastic leukemia (ALL)?

Updated: Jan 02, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Jennifer Reikes Willert, MD  more...
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Although HSCT with its graft versus leukemia (GVL) effect is the most commonly used cellular therapy, several other interventions are possible, as follows: [33]

  • Donor leukocyte infusion (DLI): T-cell DLI in a postallogeneic HSCT setting, provide GVL benefit for relapsed chronic myeloid leukemia and EBV-induced lymphoproliferative disease and, rarely, for induced durable remissions in relapsed ALL.

  • Natural killer (NK) cell infusion: NK cell infusions in the setting of haploidentical transplantations and killer cell Ig–like receptor (KIR) ligand mismatches has shown benefit in a minority of AML patients, but the value in ALL is uncertain.

  • In chimeric antigen receptor (CAR) T-cell therapy, the patient's own 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. [34] Studies of treatment with CAR T-cells targeting CD19 have reported high rates of complete and long-lasting remissions in patients with refractory acute lymphoblastic leukemia (ALL). Toxicities, which can be fatal, include cytokine release syndrome (CRS), B-cell aplasia, and cerebral edema. [34]

    In August 2017, the US Food and Drug Administration (FDA) approved the anti-CD19 CAR T-cell therapy agent tisagenlecleucel (Kymriah) for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse. Because of the risk of adverse effects, the FDA approval includes a risk evaluation and mitigation strategy, which requires special certification for hospitals and clinics that administer the treatment and additional training for their physicians and other staff. [35, 29]

    Approval of tisagenlecleucel was based on results of an open-label, multicenter single-arm trial (Study B2202). Eighty-eight children and young adults were enrolled, 68 were treated, and 63 were evaluable for efficacy. Among the 63 treated patients, 52 responded. Of these 52 responders, 40 patients (63%) had a complete response within the first 3 months after infusion, and 12 (19%) had a complete remission with incomplete blood count recovery. All of these were associated with minimum residual disease–negative status in the bone marrow. [36]

    In conjunction with the approval of tisagenlecleucel, the FDA also expanded the approval of tocilizumab to include the treatment of severe or life-threatening CRS resulting from CAR T-cell therapy in patients 2 years of age or older. In clinical trials, 69% of patients with CRS related to CAR T-cell therapy had complete resolution of CRS within 2 weeks after receiving one or two doses of tocilizumab. [29]

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