Interleukin-15-activated cytokine-induced killer cells may sustain remission in leukemia patients after allogeneic stem cell transplantation: feasibility, safety and first insights on efficacy

Eva Rettinger, Sabine Huenecke, Halvard Bonig, Michael Merker, Andrea Jarisch, Jan Soerensen, Andre Willasch, Gesine Bug, Ansgar Schulz, Thomas Klingebiel, Peter Bader, Eva Rettinger, Sabine Huenecke, Halvard Bonig, Michael Merker, Andrea Jarisch, Jan Soerensen, Andre Willasch, Gesine Bug, Ansgar Schulz, Thomas Klingebiel, Peter Bader

No abstract available

Keywords: HSCT; IL-15-activated; cytokine-induced killer cells; efficacy; immunological control; relapse.

Figures

Figure 1.

Outcome after first cytokine-induced killer (CIK) cell infusion. With the first CIK cell infusion patients were followed for a median of 9.1 months (range 0.9–36.3 months). Three out of 13 patients succumbed to transplant-related complications (TRM) apparently unrelated to CIK cell therapy (9-month CITRM 19.2%, 95%CI: 0.1%–66.4%. (A) Given historically high rates of relapse for this high-risk population within six months, a 9-month follow-up period was chosen for estimates of survival; 9-month probabilities of event-free survival (EFS) and relapse-free survival (RFS) for the 13 patients were estimated to be 61.5% (95%CI: 30.8%–81.8%) and 76.2% (95%Cl: 42.7%–91.7%), respectively (B and C). Four of 13 patients relapsed after transplantation (9-month CIR, 23.8%, 95%CI, 1.1%–63.2%. (D) All of these patients had shown molecular relapse at a median of 3.2 months (range, 2.3–4.1 months) after hematopoietic stem cell transplantation (HSCT). Hematologic relapses occurred at a median of 8.2 months (range 4–17.5 months) after transplantation suggesting that CIK cell treatment may have delayed recurrence of disease.

Figure 2.

Immune reconstitution. After cytokine-induced killer (CIK) cell treatment patients were sequentially screened for relapse, for occurrence of acute graft-versus-host-disease (aGvHD) and for T, natural killer (NK), and T-NK cell counts. Patients with treatment responses for whom immune monitoring data were available are shown. Immune monitoring demonstrated that T-cell numbers, followed by NK and to a lesser extent T-NK cell counts constantly increased after receiving more than 1×106 CD3+CD56− CIK cells/kg, which correlated with appearance of aGvHD especially in the haploidentical transplantation setting (F, H, J). In most cases T-cell counts slightly decreased 2–4 weeks after infusions, but increased thereafter above levels before infusion. During increase of immune effector cells, short-term anti-leukemic effects were observed in the matched transplantation setting (B, D, E, G) whereas in the haploidentical setting (A, C, F, H, I, J), increase of immune cells resulted in clearance of minimal residual disease (MRD) and BCR-ABL/ABL or conversion to full donor chimerism.