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

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.

Figure 1

Serum interleukin-6 (IL-6) levels increased after anti-CD19 CAR T-cell infusion.

Figure 2

Anti-CD19 chimeric antigen receptor (CAR) T-cells are effective against tyrosine kinase inhibitor (TKI)-resistant Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Figure 3

Expansion of anti-CD19 CAR T-cells in peripheral blood.

Figure 4

Electronic colonoscopy revealed mucosal congestion and edema throughout the large intestine. The pathological examination suggested chronic mucosal inflammation.