Cytokine Release Syndrome Is an Independent Risk Factor Associated with Platelet Transfusion Refractoriness after CAR-T Treatment for Relapsed/Refractory Acute Lymphoblast Leukemia

Platelet transfusion refractoriness (PTR) has been widely observed in hematopoietic stem cell transplantation (HSCT) and chemotherapy in some researches. However, PTR not only has unclear mechanism but no recognized standard treatment guidelines, even has a life-threatening effect on hematological patients. Our study is aim to evaluate the rate of PTR and related factors of PTR in patients with refractory/relapsed acute lymphocytic leukemia (R/R ALL) who received chimeric antigen receptor T cell therapy (CAR-T). We retrospectively collected the data of 49 R/R ALL patients between July 2011 and June 2019 in our single center, and divided them into chemotherapy group and CAR-T group, including 26 patients only receiving chemotherapy and 23 undergoing CAR-T therapy. All R/R ALL patients underwent multiple first lines or second lines of chemotherapies. As for CAR-T group, the fludarabine and cyclophosphamide were administrated three days to lower the tumor burden before CAR-T cell infusion. Age, sex, height, weight, the platelet count before and after transfusion, transfusion unit are all included in our data. In terms of the CAR-T group ,we also collect the peak body temperature , the peak c-reactive protein ,CRS grade , IL6 , IL10 , IFN-γ. The pre-transfusion and post-transfusion platelet count were obtained after each transfusion, the 12h CCI<5000 (corrected count increment) is used to evaluate if the patient has PTR. By chi-square test, we found 13 patients became PTR in all patients, of 2 patients (15.4%) is in chemotherapy group while 11 (84.6%) is in CAR-T group. Moreover, 7.7% (2/26) PTR in chemotherapy group is markedly lower than 47.8% (11/23) in CAR-T group (P=0.001). The associated factors with PTR in this study is cytokine release syndrome (CRS) grade. Then we found the significant elevated cytokine levels in CAR-T group. By Mann-Whitney U test, the mean levels of IL-6 in PTR group versus non-PTR group were 6.58 vs 17.91 (p<0.001). Serum mean levels of IL-10 in PTR group versus non-PTR group were 7.58 vs 16.82 respectively (p=0.001) while serum levels of IFN-γ were 6.58 versus 17.91 respectively (P<0.001). With the decline of cytokines, the 12h CCI of partial patients with PTR will be increased than before, some patients even recover to normal platelet transfusion increment. The rate of PTR in patients undergoing CAR-T therapy was much higher than those who received chemotherapy only. CRS was the only independent risk factor associated with PTR after CAR-T treatment. High serum levels of cytokines (IL-6, IL-10 and IFN-γ) during CRS might contribute to is PTR.