Clinician-to-Clinician Update Clinician-to-Clinician Update

Patient with Relapsed ALL Successfully Treated with Novel T-Cell Therapy

September 2015 - Blood and Marrow Transplantation

Contributed by Michael R. Verneris, MD

Patients with precursor B-cell acute lymphoblastic leukemia (ALL) that is either chemotherapy refractory or has relapsed after treatment for front-line ALL have a poor prognosis.1 (See p. 1 article “Breakthroughs” for further discussion of the condition.) Here we describe the case of a school-age girl with relapsed precursor B-cell ALL who was successfully treated in a clinical trial setting with chimeric antigen receptor (CAR)-modified T-cell therapy.

Patient

A 6-year-old female with precursor B-cell ALL who had undergone allogeneic hematopoietic stem cell transplantation was found to have evidence of relapse at 6 months post-transplant. Her parents agreed to enroll her in an ongoing clinical trial of CAR-modified T-cell therapy for relapsed/refractory ALL at the University of Minnesota Masonic Children’s Hospital Pediatric Blood and Marrow Transplantation Center.

Management

Peripheral-blood mononuclear cells were collected by means of apheresis. The cells were sent for CAR transduction, which proceeded without any difficulties. During the 3-week wait, the patient was maintained on lymphodepleting chemotherapy. When the CAR-modified T-cells were received, they were infused into the patient without sequelae.

One week later, she had evidence of mild lymphocytosis and hypoxia, and she experienced fevers of 103° to 104°, which lasted for about a week. At 1 month post-CAR-modified T-cell infusion, her blood counts normalized. At 3 months post-infusion, the patient had attained a complete remission with absolute B-cell aplasia. Currently, the patient receives immune globulin IV maintenance therapy. She feels well and has begun attending first grade at her local school.

Discussion

Data from 3 phase 1 trials to determine the efficacy of CAR-modified T cells as therapy for refractory/relapsed pediatric ALL recently reported complete response rates of 70% to 90% and 6-month probability of sustained response rates of 67% to 76%.2 Given these very promising results, phase 2 clinical trials are currently enrolling.

References

  1. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14:e205-217.
  2. Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125:4017-4023.
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