Donor derived CD19 CAR-T cell for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Like Comment
Read the paper

Recurrency after alloHSCT is still the most common reason for treatment failure. The salvage treatments after recurrence includes donor lymphocyte infusion(DLI) and second HSCT. However, the 1-year overall survival rates are only 20.74%1 and 23%2, respectively. There are great needs for an effective or alternative therapy. CD19 CAR-T cell therapy has produced impressive outcomes for relapsed/refractory (R/R) B cell hematological malignancies3,4. The safety and efficacy of donor derived CD19 CAR-T cell therapy to relapsed B-ALL after alloHSCT remain unclear.

Inspired by this, we designed a retrospective clinical trial which aggregated clinical data from totally nine medical centers in China, making it the largest reported case number of recurrent B-ALL (43 subjects), median follow-up of survivors was 18 months (range, 6-47 months). The outcomes are optimistic, 34 subjects (79%; 95% confidence Interval [CI], 66, 92%) achieved a complete remission. CRS occurred in 38 (88% [78, 98%]) and was ≥ grade-3 in 7. Two subjects died from multi-organ failure and CRS. Nine subjects (21% [8, 34%]) developed ≤ grade-2 ICANS with no cases > grade-2. Two subjects developed ≤ grade-2 acute GvHD. 1-year EFS and survival was 43% (25, 62%). In subjects with a complete remission 1-year probability of CIR was 41% (25, 62%; N =43) and 1-year EFS and survival was 59% (37, 81%; N =43).

Therapy of CD19-positive B-cell ALL relapsing after alloHSCT with donor-derived anti-CD19 CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes are comparable and sometimes better compared with those achieved with stopping immune suppression, DLI and/or with a second allotransplant from the same or different donor. Safety and efficacy of these strategies can only be accurately compared in a randomized trial.


  1. Vaezi M, Zokaasadi M, Shahsavari Pour S, et al. The Role of Donor Leukocyte Infusions in the Treatment of Relapsed Acute Leukemia after Allogeneic Stem Cell Transplantation: A Retrospective Analysis. Int J Hematol Oncol Stem Cell Res. 2018;12: 185–191.
  2. LM Poon, R Bassett Jr, G Rondon, et al. Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia. Bone Marrow Transplant.2013;48:666-70.
  3. Liu D. CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. J Hematol Oncol. 2019;12:113.
  4. Schuster SJ. CD19-directed CAR T cells gain traction. Lancet Oncol. 2019;20:2–3.

Xi Zhang

Director of Hematology, Xinqiao Hospital