| Objective:Applying chimeric antigen receptor T(CART)cell to treat refractory or recurrent B-acute lymphocytic leukemia(r/r B-ALL).Meanwhile,observing the efficacy and adverse reactions.Furthermore,summarize the factors of prognosis of CART cell treatment and provide a basis for further improvement of CART cell therapy.Methods:Thirty-two child patients with r/r B-ALL was treated by CART,and the clinical data of CART were retrospectively analyzed.In addition,the recurrence and death respectively were the end point event to evaluate the efficacy and safety of CART.Results:Thirty-two child patients with r/r B-ALL was treated by CART from July2017 to January 2020.Detailed clinical information as follows:23 males(71.9%)and 9females(28.1%);the median age was 7.5 years(2-17.5 years);27 recurrent B-ALL and 5refractory B-ALL;19 bone marrow recurrence including 5 secondary recurrence,2 bone marrow and testicular recurrence and 6 extramedullary recurrence including 5 testes and 1lymph node;40 times CART were received in all child patients and the median number of CART was 0.9×10~7/kg(child patients);Efficacy evaluation:the first evaluation was carried out within two weeks after CART transfusion.30 had bone marrow remission,and2 died before the first evaluation due to grade 4 CRS reaction with infection.Up to follow-up time,a total of 6 child patients relapsed including 1 treated with CART bridged hematopoietic stem cell transplantation and 5 followed up for observation after CART treatment;a total of 5 child patients died including 2 died during CART treatment due to grade 4 CRS reaction with infection and 3 died due to disease progression after recurrence.Thirty patients had 3-month RFS(96.3±3.6%),6-month RFS(81.4±8.6%)and 9-month RFS(65.3±12.5%).OS at 3,6 and 9 months was 100%,12 months was(94.7±5.1%)and24 months(76±12.8%).Bone marrow tumor load≥36%and ferritin peak≥2500 ng/ml within two weeks of CART cell reinsertion were associated with recurrence.Adverse reactions:mainly including Cytokine release syndrome(CRS)and cart-cell-related encephalopathy syndrome(CRES),CRS appeared in 26 child patients within a week of CART cell reinfusion,16 child patients of grade 1-2 and 10 of grade 3-5 according to Lee[1]classification system.CRES reaction in 12 child patients.In additional,the peaks of cytokines IL-2,IL-4,IL-6,IL-10,IFN-γ,LDH and ferritin were correlated with CRS severity.Treatment of adverse reactions:18 child patients received intravenous administration of tozumab among of them 12 with glucocorticoid.CRS and CRES reactions was relieved within a week after treatment in combination.Hormone dosage was related to the duration of remission in child patients,and the cumulative dose of methylprednisolone≥8 mg/kg had a poor prognosis.The average length of stay for child patients treated with CART was 11.4 days(4-21 days).Conclusion:1.CART cell therapy for r/r B-ALL is effective and safe,the remission rate reaches 100%,CRS and CRES responses can be alleviated after treatment;2.The higher the peak value of cytokines in CART cells within 48 hours after CART implantation,the more likely to have grade 3-4 CRS reactions.3.Bone marrow tumor load≥36%before transfusion and cumulative dose≥8 mg/kg after transfusion had poor prognosis;4.Ferritin≥2500 ng/ml within two weeks after back transfusion was associated with disease recurrence and was an independent prognostic risk factor,which could be used as a marker of poor prognosis;5.Short hospital stay for CART cell therapy. |
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