Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract

BackgroundElderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined.Case presentationWe treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy.ConclusionsOur preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned.Trial registrationAllogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550 Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0357-z) contains supplementary material, which is available to authorized users.

Donor-derived CAR-T Cells Serve as a Reduced-intensity Conditioning Regimen for Haploidentical Stem Cell Transplantation in Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: Case Report and Review of the Literature

“…The mechanism of this process could be that the G-PBSCs might support the survival of the donorderived CAR-T cells. 11,22 In the present study, we persistently detected donor CAR-T cells in the host peripheral blood after the first infusion of CAR-T cells at a peak level on day 7. Although the CAR-T cells gradually decreased, the CAR-T cells could still be detected until day 40 after infusion.…”

Use of Chimeric Antigen Receptor T Cells in Allogeneic Hematopoietic Stem Cell Transplantation

“…The outcome is also poor for a patient with a higher burden of disease [34]. In addition, it is very difficult to collect sufficient T cells for the construction of CAR-T cells from patients who have an extremely high leukemia burden [23,35].…”

“…Therefore, the donor-CAR-T cells may be safe and effective in allo-HSCT. Recently, Ai et al reported an older patient with refractory ALL, who was treated with low numbers of donor-derived CD19-CAR-T cells and with low dose of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood stem cells [35]. This patient developed serious GVHD and by treating with anti-GVHD drugs, the related complication was controlled.…”

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation

“…Novel approaches comprise complex combinations as well as sequences of defined cellular products. A case report of a patient with relapsed and refractory B-cell ALL described a combined treatment composed of re-induction chemotherapy, haploidentical co-infusion of CD19-CAR T cells, and mobilized peripheral blood stem cells followed by MSC infusion [91], giving a first example of a highly complex composition of cellular therapy. However, large clinical trials comparing such treatment modalities are often missing and are highly challenging due to the complexity of the therapeutic agent.…”