scholarly journals Cytokine Release Syndrome Is an Independent Risk Factor Associated With Platelet Transfusion Refractoriness After CAR-T Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yadan Liu ◽  
Bin Liang ◽  
Yan Liu ◽  
Guoqing Wei ◽  
Wenjun Wu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Platelet Transfusion ◽  
Independent Risk Factor ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T ◽  
Grade 3 ◽  
Platelet Transfusions

Background: Chimeric antigen receptor T cell (CAR-T) therapy is successful in improving treatment outcomes for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, toxicities associated with CAR-T therapy are being increasingly identified. Pancytopenia is one of the most common complications after CAR-T therapy, and platelet transfusions are an essential part of its supportive care.Study Design and Methods: This study aimed to assess the effectiveness of platelet transfusions for R/R ALL patients at our single center and identify associated risk factors. Overall, 44 R/R ALL patients were enrolled in this study, of whom 26 received CAR-T therapy and 18 received salvage chemotherapy.Result: Patients in the CAR-T group had a higher incidence of platelet transfusion refractoriness (PTR) (15/26, 57.7%) than those in the chemotherapy group (3/18, 16.7%) (p = 0.007). For patients receiving CAR-T therapy, multivariate analysis showed that the grade of cytokine release syndrome (CRS) was the only independent risk factor associated with PTR (p = 0.007). Moreover, higher peak serum IL-6 and IFN-γ levels suggested a higher risk of PTR (p = 0.024 and 0.009, respectively). Patients with PTR received more platelet infusion doses than those without PTR (p = 0.0426). Patients with PTR had more grade 3–4 bleeding events than those without PTR (21.4 vs. 0%, p = 0.230), and the cumulative incidence of grade 3–4 bleeding event was different (p = 0.023).Conclusion: We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions.

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

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2448-2448
Author(s):  
Yadan Liu ◽  
Yongxian Hu ◽  
He Huang
Keyword(s):  
Risk Factor ◽  
Platelet Transfusion ◽  
Independent Risk Factor ◽  
Group Versus ◽  
Serum Levels ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Chemotherapy Group ◽  
Car T ◽  
Ifn Γ

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. Disclosures No relevant conflicts of interest to declare.

scholarly journals Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengxin Luan ◽  
Junjie Zhou ◽  
Haixia Wang ◽  
Xiaoyu Ma ◽  
Zhangbiao Long ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T ◽  
Local Cytokine

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.

scholarly journals Extracorporeal cytokine removal in chimeric antigen receptor T-cell therapy associated cytokine release syndrome in patient with acute lymphoblastic leukemia. Case report

2021 ◽  
Vol 93 (7) ◽  
pp. 811-817
Author(s):  
Antonina E. Shchekina ◽  
Gennadii M. Galstyan ◽  
Olga A. Gavrilina ◽  
Natalia M. Arapova ◽  
Svetlana Iu. Bronyakina ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Multiple Organ ◽  
Common Complication ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Common

Сytokine release syndrome is the common complication of CAR-T therapy. We report a case of patient with B-cell acute lymphoblastic leukemia developing сytokine release syndrome with shock and multiple organ failure and requiring cytokine removal and hemodiafiltration. Remission of the disease was achieved after CAR-T therapy.

scholarly journals Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

2016 ◽  
Vol 34 (36) ◽  
pp. 4381-4389 ◽  
Author(s):  
Arend von Stackelberg ◽  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Rupert Handgretinger ◽  
Tanya M. Trippett ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Recommended Dosage ◽  
Disease Response ◽  
Grade 3 ◽  
Minimal Residual

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

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