Molecular remission using low-dose immunotherapy for relapsed refractory Philadelphia chromosome-positive precursor B-cell acute lymphoblastic leukemia post-allogeneic stem cell transplant

Abstract

Adults with relapsed/refractory acute lymphoblastic leukemia have a poor prognosis. While current immunotherapies are promising, they are toxic, with graft-versus-host disease a major complication of allogeneic therapy. Here, we report a patient with high-risk relapsed/refractory Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (ALL) following chemotherapy induction, matched related donor allogeneic hematopoietic stem cell transplantation (allo-HCT), donor lymphocyte infusion and two tyrosine kinase inhibitors. The patient achieved a complete molecular and cytogenetic remission with minimal adverse events or evidence of GVHD following recombinant human IL-2 (rIL-2), in combination with a tyrosine kinase inhibitor (TKI). There was a ninefold increase in natural killer (NK) cell activity and natural killer T cells (NKT) cells (CD2 ⁺CD26 ⁺). Personalized low dose recombinant human IL-2-mediated NK cell stimulation represents an effective, nontoxic immunotherapy administered in the outpatient setting for relapsed acute lymphoblastic leukemia and warrants further investigation.

Lay abstract

Recurrent or refractory adult acute lymphoblastic leukemia (ALL) is often associated with dismal outcomes after standard treatment. Despite great progress in recent immunotherapy approaches, ALL patients encounter a therapeutic challenge due to the toxicity and complications of these new treatments. We report a patient with high-risk relapsed/refractory Philadelphia chromosome-positive B-cell ALL following standard treatment and in whom a personalized immunotherapy treatment resulted in molecular remission with minimal side effects and maintenance of immune tolerance. This nontoxic treatment approach can be used to treat patients with relapsed/refractory ALL and needs to be evaluated in future research.

Abstract

Personalized low-dose recombinant human IL-2 (rIL-2)-mediated natural killer (NK) cell stimulation, in combination with a tyrosine kinase inhibitor (TKI), resulted in activation of effector NK cells and an increase in IFN-γ and (T cells + NK cells expressing dipeptidyl peptidase) levels. The CD4 ⁺CD25 ⁺ regulatory T cells (Tregs) showed a progressive decrease. This personalized treatment approach which targeted Ph+ acute lymphoblastic leukemia t (9; 22) resulted in molecular remission with minimal side effects.