title: Superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in newly diagnosed patients with B cell indolent lymphomas: long-term results from a single center in China.
abstract: BACKGROUND
  Rituximab has been confirmed to improve the survival of patients with B cell indolent non-Hodgkin lymphomas (B-iNHLs) in Western world as previously reported, however, it is rarely reported in Chinese cohort. This study is to investigate the efficacy and safety of rituximab-based chemoimmunotherapy and select subpopulations most sensitive to the regimen in Chinese B-iNHL patients.
  
  
  METHODS
  334 B-iNHL patients from our center were retrospectively assessed.
  
  
  RESULTS
  Patients received R-based chemoimmunotherapy showed significantly higher rates of overall response (OR) (93.0% vs. 53.4%, P < 0.001) and complete response (CR) (63.3% vs. 16.0%, P < 0.001) compared with the patients received other therapies. Survival analysis showed that rituximab-based chemoimmunotherapy could obviously improve the progression-free survival (PFS) (110 vs. 49 months, P = 0.001) and overall survival (OS) (120 vs. 72 months, P < 0.001) in patients with B-iNHLs. Interestingly, in chronic lymphocytic leukemia (CLL) patients, we found that the patients with β2-microglobulin (β2-MG) < 3.5 mg/L, lactate dehydrogenase (LDH) < 220 U/L, zeta-chain-associated protein kinase 70 (ZAP-70) negative, and non high-risk genetic abnormality could achieve more benefits from R-based regimens with higher CR rate (P = 0.003, 0.029, 0.013 and 0.038, respectively). Meanwhile, more CLL patients achieved minimal residual disease (MRD) negative after rituximab-based treatment (46.5% vs. 10.3%, P < 0.001). Moreover, CLL patients with MRD < 1%, LDH < 220 U/L, complete remission (CR) or partial remission (PR), β2-MG < 3.5 mg/L and non high-risk cytogenetic abnormality showed superior outcome compared to the controls (P = 0.001, 0.000, 0.000, 0.001 and 0.013, respectively). No other side-effects increased in chemoimmunotherapy group except the elevation of grade 3-4 neutropenia.
  
  
  CONCLUSIONS
  Our results demonstrate the superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in Chinese cohort with newly diagnosed B-iNHLs and further identify subpopulations that are more sensitive to R-based chemoimmunotherapy in CLL group.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. zengjunli@163.com.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. yx021021@sina.com.|Department of Hematology, The First Affiliated Hospital of Nanchang University, NanChang, 330006, China. yx021021@sina.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. shuhuayilove@163.com.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yi
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. zhimingoo@gmail.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. yuyuzhen2003@yahoo.com.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. yanzi_zjyl@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. fxy308@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. benrun@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. zoudehui72@163.com.
authors.forename: Dehui
authors.initials: D
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. qi_jy@yahoo.com.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. fenghuang-zhan@uiowa.edu.
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China. drqiu99@medmail.com.cn.|Umbilical Cord Blood Bank of Tianjin, Tianjin, 300020, China. drqiu99@medmail.com.cn.
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D002681:China; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; D011241:Prednisone