Anti-CD19 chimeric antigen receptor T-cell therapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia: Two case reports

Medicine (Baltimore). 2016 Dec;95(51):e5676. doi: 10.1097/MD.0000000000005676.

Abstract

Rationale: The presence of the Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (ALL) has been associated with a high risk of disease relapse and a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for adults with Ph-positive ALL, but relapse remains the primary cause of treatment failure, and is associated with an extremely poor prognosis. The emergence of resistance to tyrosine kinase inhibitors (TKIs) poses a challenge for patients with disease relapses after initial treatment with TKI-containing regimens.

Patient concerns: Two patients with TKI-resistant recurrent Ph-positive ALL.

Diagnoses: Ph-positive ALL.

Interventions: Anti-CD19 CAR T-cell infusion.

Outcomes: One patient's bone marrow blasts decreased significantly, and the other reached negative minimal residual disease (MRD). However, we first recorded the development of new-onset acute graft-versus-host disease (aGVHD) after anti-CD19 CAR T-cell infusion in a patient who received allogeneic HSCT. Our 2 case reports also demonstrate the efficacy of anti-CD19 CAR T-cell therapy in the treatment of TKI-resistant Ph-positive ALL.

Lessons: Our report suggests that anti-CD19 CAR T-cell therapy may be a promising option for the treatment of relapsed Ph-positive ALL after conventional chemotherapy or allogeneic HSCT. However, caution is due given the possibility of the adverse effects of cytokine release syndrome (CRS)-induced aGVHD for patients receiving allogeneic HSCT.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Interleukin-6 / blood
  • Male
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Receptors, Antigen, T-Cell / immunology*
  • Treatment Outcome

Substances

  • CD19-specific chimeric antigen receptor
  • Interleukin-6
  • Receptors, Antigen, T-Cell