Positive impact of high-throughput drug sensitivity assay and salvage
autologous CD19 CAR-T therapy on second marrow relapse of acute
lymphoblastic leukemia with NT5C2 mutation
Abstract
Background: A 12-year-old girl diagnosed with intermediate risk B-ALL in
2017 received chemotherapy according to CCLG-2008 ALL protocol and
achieved a complete remission (CR) after induction. However, four years
later, she had a first bone marrow relapse and received treatment with
HKPHOSG Relapsed ALL 2007 protocol. During maintenance chemotherapy,
approximately one year after the first relapse, she developed a second
bone marrow relapse with NT5C2 gene mutation detected. Tumor burden was
not well controlled after DEAV chemotherapy, with the blasts in bone
marrow increasing from 49.3% to 96%. The analysis of high-throughput
drug sensitivity of tumor resistant genes was consistent with the poor
response to chemotherapy. Procedure: CAR-T cell immunotherapy bridged to
HSCT was introduced at this stage. Following peripheral lymphocyte
apheresis, the patient received lymphodepleting conditioning with
fludarabine and cyclophosphamide three days before CAR-T cell infusion.
Dexamethasone and carfilzomib were then given according to the outcome
of high-throughput drug sensitivity test. Result: Around 68.6% blasts
were detected by flow cytometry at the day of CAR-T cell infusion. The
patient experienced grade 1 CRS without ICANS. CR of morphology and
molecule biology was achieved on day 28 after CAR-T cell infusion.
Finally the child received haploid-HSCT and remained in remission.
Conclusion: Overall, this report reveals that the combination of drug
sensitivity test with lymphodepleting conditioning could significantly
reduce the tumor burden before infusion of CART cells, and patients may
achieve deeper remission and obtain opportunity for transplantation.