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

Abstract

Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT.

HLA-matched and HLA-haploidentical allogeneic CD19-directed chimeric antigen receptor T-cell infusions are feasible in relapsed or refractory B-cell acute lymphoblastic leukemia before hematopoietic stem cell transplantation

“…Three cases have been reported to have received HCART19 cells before allo-HSCT [5][6][7]. Two case reports have shown that the use of HCART19 cells as part of a conditioning regimen for allo-HSCT has beneficial therapeutic effects [6,7]. In another case involving the HCART19 cells, no myeloablative conditioning regimen was used, and the patient had a mild response to treatment, which is consistent with the responses we observed [5].…”

“…Patient 6 exhibited subcutaneous tissue infiltration in the right upper limb, and the infiltrating lesion was alleviated after HCART19 cell infusion. Three cases have been reported to have received HCART19 cells before allo-HSCT [5][6][7]. Two case reports have shown that the use of HCART19 cells as part of a conditioning regimen for allo-HSCT has beneficial therapeutic effects [6,7].…”

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

“…Therefore, it must be careful when using the immunosuppressors because of their potential effect in killing CAR-T cells and inhibiting the proliferation of CAR-T cells during transplantation. In this study, the immunosuppressors of mycophenolate mofetil and tacrolimus were changed from day 7 to day 1 after the 7th day of the first infusion of CAR-T cells, which was adopted to avoid or alleviate the killing effect and the inhibition of the proliferation of the CAR-T cells [39]. The ATG) can also kill and inhibit the proliferation of CAR-T cells.…”

“…It is still not clear that whether donor-derived CAR-T cells should be used during allo-HSCT as a part of conditioning regimens because of the related complications, such as CRS and GVHD, especially for patients with high leukemia burden who can collect enough T cell for the construction of CAR-T cells. In our center, a 12-year-old girl with refractory/relapsed ALL was treated with donor-derived CD19-CAR-T cells as a reduced-intensity conditioning regimen for haploidentical transplantation [39]. This patient received a reduced-intensity conditioning regimen, then infusion with equal dose future science group www.futuremedicine.com of the donor-derived CD19-CAR-T cells for 4 days infusion with total dose of 6.4 × 10 6 /kg.…”

Study on the Prognostic Value of Aberrant Antigen in Patients With Acute B Lymphocytic Leukemia

“…Multiple clinical trials have shown that T cells programmed to express anti-CD19 CAR-T cells have curative potential against relapsed B-cell malignancies. [14][15][16][17][18] With the accumulation of clinical treatment data, some patients had ineffective results in treatment with CAR-T cells, especially those who relapsed after treatment with CAR-T cells. 19,20 CD19 antigen reduction or escape is the main cause of the failure of CAR-T cells therapy.…”