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Additional file 6: Table S3. Univariate and multivariate analysis for overall survival duration.

Additional file 5: Table S2. The CR rate of AML with different burdens of IKZF1 mutation.

Additional file 4: Table S1. IKZF1-mutated AML patients in our cohort.

Additional file 9: Table S6. The influence of IKZF1 mutation on AML with different SF3B1-mutated status.

Additional file 8: Table S5. The influence of IKZF1 mutation on AML with different CEBPA-mutated status.

Additional file 7: Table S4. The influence of IKZF1 mutation on AML with different CSF3R-mutated status.

Hui Liu,1,2,* Chunmei Yang,2,3,* Xiaoyan Zhao,2,4 Jing Le,5 Gongqiang Wu,6 Juying Wei,2,3 Yun Liang,1 Wenbin Qian1,2 1Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, People’s Republic of China; 2Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 31003, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People’s Republic of China; 4Department of Hematology, First Affiliated Hospital of Jiaxing University, Jianxing, Zhejiang 314000, People’s Republic of China; 5Department of Hematology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, People’s Republic of China; 6Department of Hematology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang People’s Hospital, Dongyang, Zhejiang 322100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenbin Qian; Yun LiangDepartment of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of ChinaTel +86-571-89713674Email qianwb@zju.edu.cn; liangyun@zdu.edu.cnPurpose: Diffuse large B cell lymphoma (DLBCL) is an aggressive B-cell malignancy with clinical and molecular heterogeneity whose genetics may have clinical implications for patient stratification and treatment. The circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker harboring tumor-derived genetic alterations that are identical to those of tumor cells, thus showing great promise in individualized medicine, including precise diagnosis, prediction of prognosis, response monitoring, and relapse detection for DLBCL.Patients and Methods: In this study, we applied NGS analysis to tumor biopsies and ctDNA samples from 16 DLBCL subjects. Then, we compared the genomic alterations from 41 newly diagnosed patients and 56 relapsed/refractory (R/R) patients.Results: Our results show that ctDNA can function as a liquid biopsy for tracking recurrently mutated genes in DLBCL (sensitivity: 87.50%). The mutational profiles of newly diagnosed and R/R DLBCL groups largely overlapped, but the frequencies of some gene mutations differ between the two cohorts. The distribution of mutations also revealed different frequencies in the two cohorts due to different signaling pathways. Genes from apoptosis pathway, immune response and BCR pathway suffered more mutations in R/R patients.Conclusion: Overall, this study establishes ctDNA as an easily accessible source of tumor DNA for DLBCL genotyping and provides a deeper understanding of the somatic alteration spectrum for both newly diagnosed and R/R DLBCL patients.Keywords: diffuse large B cell lymphoma, circulating tumor DNA, liquid biopsy, next-generation sequencing, mutation

Additional file 1: Table S1. Adverse events grade 3–4.

Chunmei Yang,1,* Wen Lei,1,2,* Hongqiong Xie,1,* Gongqiang Wu,3 Juying Wei,1 Aibin Liang,4 Wenbin Qian1,2,5 1Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People’s Republic of China; 2Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, People’s Republic of China; 3Department of Hematology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang 322100, Zhejiang, People’s Republic of China; 4Department of Hematology, Tongji Hospital of Tongji University, Shanghai 200065, People’s Republic of China; 5National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aibin LiangDepartment of Hematology, Tongji Hospital of Tongji University, Shanghai, People’s Republic of ChinaEmail lab7182@tongji.edu.cnWenbin QianDepartment of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaEmail qianwb@zju.edu.cnAbstract: Relapsed and refractory (R/R) mantle cell lymphoma (MCL) remains an incurable lymphoma with a poor prognosis. Recently, there are a few studies demonstrating the efficacy of anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy in MCL, including ZUMA-2 study in which CD28-based CAR-T cells were used. However, long-term efficacy and safety associated with 4-1BB-based CAR-T therapy in MCL are not defined well. Here, we report three male patients with R/R classical MCL, who received CD19-directed 4-1BB CAR-T therapy and achieved complete remission, showed mild symptoms of cytokine-release syndrome (CRS) and had no neurological toxicity. During a follow-up of 24– 35 months, all three patients remained in complete remission. Persistent B-cell depletion was observed in two patients. Recovery of CD19+ polyclonal B cells was detected in one patient at 6 months after CAR-T cell infusion. Recovery of serum immunoglobulin, including IgG, IgA and IgM, was not observed in two patients at the last follow-up. Only one patient developed herpes zoster, and the other two patients had no serious infection. This is the first report about the efficacy, long-term remission and safety of CD19-directed 4-1BB CAR-T therapy in R/R MCL.Keywords: mantle cell lymphoma, CAR-T cell therapy, long-duration remission, B-cell depletion