Your browser doesn't support javascript.
loading
Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.
Hu, Yongxian; Zhang, Mingming; Yang, Tingting; Mo, Zhuomao; Wei, Guoqing; Jing, Ruirui; Zhao, Houli; Chen, Rongrong; Zu, Cheng; Gu, Tianning; Xiao, Pingnan; Hong, Ruimin; Feng, Jingjing; Fu, Shan; Kong, Delin; Xu, Huijun; Cui, Jiazhen; Huang, Simao; Liang, Bin; Yuan, Xiaolin; Cui, Qu; Guo, Hongshan; Yu, Yunxian; Feng, Youqin; Jin, Chunxiang; Ren, Jiangtao; Chang, Alex H; Wang, Dongrui; Huang, He.
Affiliation
  • Hu Y; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Zhang M; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Yang T; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Mo Z; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Wei G; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Jing R; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Zhao H; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Chen R; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Zu C; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Gu T; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Xiao P; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Hong R; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Feng J; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Fu S; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Kong D; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Xu H; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Cui J; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Huang S; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Liang B; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Yuan X; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Cui Q; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Guo H; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Yu Y; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Feng Y; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Jin C; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Ren J; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Chang AH; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Wang D; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
  • Huang H; From the Bone Marrow Transplantation Center, First Affiliated Hospital, and Liangzhu Laboratory, Zhejiang University School of Medicine (Y.H., M.Z., T.Y., Z.M., G.W., R.J., H.Z., R.C., C.Z., T.G., P.X., R.H., J.F., S.F., D.K., H.X., J.C., S.H., X.Y., H.G., Y.F., C.J., D.W., H.H.), the Institute of H
N Engl J Med ; 390(16): 1467-1480, 2024 Apr 25.
Article in En | MEDLINE | ID: mdl-38657244
ABSTRACT

BACKGROUND:

Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear.

METHODS:

We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored.

RESULTS:

After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100).

CONCLUSIONS:

Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia / Immunotherapy, Adoptive / Hematopoietic Stem Cell Transplantation / Receptors, Chimeric Antigen / Graft vs Host Disease / Lymphoma Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2024 Document type: Article Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia / Immunotherapy, Adoptive / Hematopoietic Stem Cell Transplantation / Receptors, Chimeric Antigen / Graft vs Host Disease / Lymphoma Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: N Engl J Med Year: 2024 Document type: Article Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA