Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia
Bo Cai, Mei Guo, Yao Wang, Yajing Zhang, Jun Yang, Yelei Guo, Hanren Dai, Changlin Yu, Qiyun Sun, Jianhui Qiao, Kaixun Hu, Hongli Zuo, Zheng Dong, Zechuan Zhang, Mingxing Feng, Bingxia Li, Yujing Sun, Tieqiang Liu, Zhiqing Liu, Yi Wang, Yajing Huang, Bo Yao, Weidong Han, Huisheng Ai, Bo Cai, Mei Guo, Yao Wang, Yajing Zhang, Jun Yang, Yelei Guo, Hanren Dai, Changlin Yu, Qiyun Sun, Jianhui Qiao, Kaixun Hu, Hongli Zuo, Zheng Dong, Zechuan Zhang, Mingxing Feng, Bingxia Li, Yujing Sun, Tieqiang Liu, Zhiqing Liu, Yi Wang, Yajing Huang, Bo Yao, Weidong Han, Huisheng Ai
Abstract
Background: Elderly 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 presentation: We 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.
Conclusions: Our 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 registration: Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550.
Keywords: Allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells; B cell acute lymphoblastic leukemia (B-ALL); Case report; Haplo-identical mobilized peripheral blood stem cell infusion; Relapsed and refractory.
Figures
References
- Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517. doi: 10.1056/NEJMoa1407222.
- Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–528. doi: 10.1016/S0140-6736(14)61403-3.
- Qasim W, Amrolia PJ, Samarasinghe S, Ghorashian S, Zhan H, Stafford S, et al. First clinical application of talen engineered universal CAR19 T cells in B-ALL. Blood. 2015;126:2046.
- Guo M, Hu KX, Liu GX, Yu CL, Qiao JH, Sun QY, et al. HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: long-term follow-up. J Clin Oncol. 2012;30:4084–4090. doi: 10.1200/JCO.2012.42.0281.
- Guo M, Hu KX, Yu CL, Sun QY, Qiao JH, Wang DH, et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood. 2011;117:936–941. doi: 10.1182/blood-2010-06-288506.
- Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34:1112–1121. doi: 10.1200/JCO.2015.64.5929.
- Dai H, Zhang W, Li X, Han Q, Guo Y, Zhang Y, et al. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Oncoimmunology. 2015;4:e1027469. doi: 10.1080/2162402X.2015.1027469.
- Guo M, Sun Z, Sun QY, Han Q, Yu CL, Wang DH, et al. A modified haploidentical nonmyeloablative transplantation without T cell depletion for high-risk acute leukemia: successful engraftment and mild GVHD. Biol Blood Marrow Transplant. 2009;15:930–937. doi: 10.1016/j.bbmt.2009.04.006.
- Marcus A, Eshhar Z. Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer. Expert Opin Biol Ther. 2014;14:947–954. doi: 10.1517/14712598.2014.900540.
- Chen HR, Ji SQ, Wang HX, Yan HM, Zhu L, Liu J, et al. Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell depletion. Exp Hematol. 2003;31:1019–1025. doi: 10.1016/S0301-472X(03)00228-5.
- Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I, et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000;95:83–89.
- Li Pira G, Di Cecca S, Montanari M, Moretta L, Manca F. Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives. Blood Rev. 2016;30:297–307. doi: 10.1016/j.blre.2016.03.001.
- Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123:2343–2354. doi: 10.1182/blood-2013-09-529537.
Source: PubMed