Chronic lymphocytic leukemia is a chronic B-lymphocytic proliferative disease with accumulation of mature-like small lymphocytes in peripheral blood, bone marrow and lymphoid tissue and corresponding clinical symptoms. At present, the main authoritative guidelines for the clinical management of CLL in China include the expert consensus and guidelines on CLL issued by China, the United States and the International Working Group on Chronic Lymphoma (iwCLL). In this article, we mainly interpret the CLL section in the Chinese Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (2011 edition), the CLL guidelines published by iwCLL in 2008, and the National Comprehensive Cancer Network (NCCN) 2014 4th edition guidelines for the treatment of non-Hodgkin’s lymphoma, and combine them with the authors’ own clinical CLL treatment experience. Definition and diagnostic criteria Overall, the current definition of CLL basically follows the recommendations of the World Health Organization (WHO) on the classification of tumors of the lymphohematopoietic system issued in 2008, and CLL refers to a chronic lymphoproliferative disease with homogeneous, slightly irregular small B lymphocytes infiltrating in peripheral blood, bone marrow, spleen and lymph nodes. Small lymphocytic lymphoma (SLL) is considered to be the same disease as CLL, and the difference between the two mainly lies in the clinical manifestations: the initial onset of CLL is mainly manifested by peripheral blood and bone marrow infiltration; while SLL is mainly manifested by lymphoma such as enlargement of lymph nodes, spleen and other lymphoid organs. And it is emphasized that currently CLL/SLL only refers to lymphoproliferative diseases originating from mature B cells, and does not include the previous lymphoproliferative diseases originating from mature T lymphocytes. The minimum requirement for the diagnosis of CLL is persistent (3 months) peripheral blood B lymphocytes ≥ 5 × 109/L (NCCN guidelines require monoclonal B lymphocytes), and the clonality of B cells is required to be confirmed by flow cytometry. The characteristic morphology of the peripheral blood smear is mature small lymphocytes, which generally have less cytoplasm, tight nuclear chromatin, and no obvious nucleoli, sometimes mixed with large, atypical cells, dividing cells, or up to 55% juvenile lymphocytes (PLL is diagnosed when the proportion of juvenile lymphocytes in peripheral blood is ≥55% of lymphocytes), in addition to smear cells, which are more common in CLL (parenchymal cellular debris ). Monoclonal B lymphocytosis (MBL) is diagnosed in patients with the presence of clonal B cells in the peripheral blood, but with an absolute clonal B count <5×109/L, without concomitant enlargement of lymph nodes (<1.5 cm) and organs, hematocrit and other disease-related symptoms.The diagnosis of SLL is subject to (1) enlargement of lymph nodes and/or spleen; (2) peripheral blood B lymphocytes < 5×109/L; (3) the same immunophenotype as CLL; (4) no hematocrit due to bone marrow infiltration of SLL cells; considering that SLL is mostly accompanied by lymph node enlargement clinically, it is recommended to perform histopathology to further confirm the diagnosis when possible. The immunophenotype of typical CLL/SLL should be CD19+, CD5+, CD23+, CD10-, CD20dim+, sIgdim+, CyclinD1-. For some CLL with atypical immunophenotype, such as CD23-/dim, sIgbright, CD20bright, etc., it is recommended to use immunohistochemistry and/or fluorescence in situ hybridization (FISH) to detect Cyclin D1 expression to differentiate it from mantle cell lymphoma (MCL). Cytogenetic and molecular biology tests: Since most patients with CLL have cytogenetic abnormalities and are important for the treatment and prognosis of CLL, the guidelines recommend a comprehensive cytogenetic evaluation, including conventional karyotyping and fluorescence in situ hybridization (FISH) techniques, for patients with initial CLL with del(11 For patients with CLL with del(11) or del(17p), the prognosis is poor and a more aggressive treatment strategy is needed; in terms of molecular biology, IGHV mutation status, CD38 molecular expression and ZAP70 are recommended routinely because they are the classical prognostic indicators of CLL, in addition to the recent findings of biased IGHV use in CLL cells, CLL molecular mutations (SF3B1, NOTCH1 etc.) are closely related to CLL treatment response and prognosis, and relevant studies can be carried out in units with conditions. In addition, the following tests need to be completed before treatment for CLL patients: (1) Complete physical examination, medical history and comprehensive assessment of the patient's physical status and concomitant diseases. (2) Evaluation of serological parameters: LDH, β2-microglobulin, thymidine kinase 1 (TK1), etc. (3) A comprehensive virological evaluation is recommended for CLL patients who may require treatment with rituximab, with the main focus on HBV-related indicators in China. Patients under certain conditions need to have the following additional tests: (1) quantitative testing of immunoglobulins. (2) Hemolysis-related tests such as reticulocyte, binding bead protein and Coombs test. (3) Bone marrow smear and biopsy are recommended for patients with clinical hematocrit to accurately determine the cause of hematocrit, and some literature suggests that the mode of bone marrow infiltration of CLL cells may be related to prognosis. (4) Whole-body imaging, whole-body enhanced CT scan is recommended, and PET/CT may be considered for patients with high clinical suspicion of Richter transformation to guide lymph node biopsy sites and clinical treatment. Treatment CLL is an inert lymphoma and therefore patients must be evaluated in detail before treatment to determine if they have an indication for treatment. The current indications for CLL treatment are mainly based on the iwCLL 2008 criteria, with minor modifications to national guidelines, as follows: 1. evidence of progressive bone marrow failure as evidenced by a progressive decrease in hemoglobin and/or platelets; 2. giant spleen (e.g., >6 cm below the left costal margin) or progressive or symptomatic splenomegaly; 3. giant lymph node enlargement (e.g., >10 cm in longest diameter) or Progressive or symptomatic lymph node enlargement; 4. Progressive lymphocytosis, such as 50% increase within 2 months, or lymphocyte doubling time (LDT) <6< span=""> months. LDT alone cannot be used as an indication for treatment when the initial lymphocyte count is <30×109< span="">/L; 5. Lymphocyte count >200×109/L or presence of leukocyte stasis symptoms; 6. Autoimmune hemolytic anemia (AIHA) and/or thrombocytopenia; (ITP) poor response to corticosteroids or other standard therapy; 7. Presence of at least one of the following Disease-related symptoms: (i) weight loss ≥10% without apparent cause within the previous 6 months; (ii) severe fatigue (e.g., ECOG physical status ≥2; inability to perform routine activities); (iii) temperature >38.0°C for more than 2 weeks without evidence of infection; (iv) night sweats for more than 1 month without evidence of infection; 8. Patient preference; 9. Clinical trials. Stratified treatment The most advanced area for CLL in recent years is the introduction of the concept of stratified treatment and the emergence of new therapeutic drugs. The first is the stratification of treatment based on general physical status and concomitant diseases, including a comprehensive assessment of age, physical status (ECOG score) and concomitant diseases (cumulative disease score, CIRS), and for patients with good general status, a multi-drug combination treatment strategy can be considered, while for patients with poorer status, low-intensity treatment is generally used; the second is the stratification of treatment based on patients’ cellular The second is the stratification of treatment based on the patient’s cellular genetics and molecular biology, and a more aggressive treatment strategy is recommended for CLL patients with high-risk genetic and molecular biology features, specifically: (1) For CLL patients with frailty and significant concomitant disease: because they cannot tolerate treatment regimens containing purine analogs, the recommended treatment regimen is targeted drugs combined with oral chemotherapeutic agents, or monotherapy strategies The treatment regimens include Obinutuzumab (GA101) or Rituximab in combination with oral phenylephrine, and monotherapy regimens may also be considered. (2) Patients without Del(17p) or Del(1lq): conventional chemotherapy + immunotherapy is recommended, with most patients ≥70 years of age or with concomitant disease (CIRS >6) recommended for targeted agents in combination with low-intensity chemotherapy agents, or monotherapy strategies, specifically Obinutuzumab (GA101) or rituximab in combination with oral benztropine nitrogen mustard; low-dose bendamustine ± rituximab (BR); CP (cyclophosphamide + prednisone) regimen ± rituximab; fludarabine ± rituximab; or rituximab, cladribine, or nitrogen mustard phenylbutyrate monotherapy; for patients aged <70< span=""> years or ≥70 years without severe concomitant disease (CIRS<6< span=""> score) Patients are recommended to use combination immunochemistry, with the main regimens being FCR (fludarabine + cyclophosphamide + rituximab), FR, PCR (pentostatin + cyclophosphamide + rituximab), BR, and Obinutuzumab in combination with oral benztropine. (3) Patients with Del(17p): There is no standard treatment for this group of patients due to their low response to all current treatments, and participation in clinical studies is recommended. The guidelines suggest that the following regimens may be considered: alemtuzumab ± rituximab, FCR, FR, HDMP + rituximab, Ibrutinib or Obinutuzumab in combination with oral nitrogen mustard phenylbutyrate are recommended for patients who have achieved CR/PR with induction therapy if they have an HLA-completely matched donor and are physically able to do so, including reduced pretreatment Allogeneic hematopoietic stem cell transplantation including reduced pretreatment intensity. (4) Patients with Del(11q): Since retrospective studies have shown that such patients have better efficacy with alkylating agent-containing regimens, a combination of targeted agents + alkylating agents is recommended for such patients. (5) Patients with unknown cytogenetics, due to the uneven development of medical level in China, some primary hospitals are unable to carry out cytogenetic analysis, for the treatment of such patients can temporarily refer to the recommended regimen for patients without Del(17p) or Del(1lq), but we need to emphasize the need to try to preserve the patient specimens and send them to higher level hospitals for testing, once the cytogenetic analysis results are obtained, it is recommended to treatment according to the corresponding recommendations. (6) Relapsed refractory patients: Firstly, for relapsed refractory patients it is recommended to re-evaluate cytogenetic and histopathological examinations, and for patients with distant relapses (there is no exact definition of the time of distant relapses, but empirically it is reasonable to use strong regimens such as FCR for >3 years, while it is more reasonable to use single drug regimens such as nitrogen mustard phenylbutyrate for 18-24 months) the original For patients with short-term relapses, due to the poor response to first-line therapy, in principle, choose therapeutic agents that are not cross-resistant to first-line regimens, novel agents or participate in clinical trials, such as Ibrutinib, Idelalisib combined with rituximab, Ofatumumab, lalidomide ± rituximab, reduced dose FCR and PCR regimens, HDMP in combination with rituximab and alemtuzumab-containing regimens, etc. Patients with short-term disease progression are considered high-risk CLL patients, and allogeneic HSCT is recommended as consolidation therapy for patients treated with CR/PR who have a fully compatible HLA donor and are physically able to do so. (7) For patients with pathological tissue biopsy confirmed large cell transformation (Richter syndrome), due to the high aggressiveness of the disease, rapid clinical progression and short patient survival, more aggressive treatment strategies are needed, such as the use of aggressive lymphoma treatment regimens such as diffuse large B-cell lymphoma or intense treatment regimens such as R-Hyper-CVAD, and conditional patients can be considered for allogeneic hematopoietic stem cell transplantation. Supportive and adjuvant therapy Because of the older age of CLL patients, the low immunity of the body and the factors of treatment, patients are mostly in a more severe state of immunosuppression and have a high incidence of treatment-related toxicities, especially infection-related diseases, so active and effective supportive and adjuvant therapy can help patients reduce treatment-related risks and improve their survival and survival quality, specifically: (1) If patients (1) If patients develop recurrent pulmonary infections, consider infusion of gammaglobulin while using antibiotics to make the patient’s IgG > 5g/L. (2) For CLL patients treated with purine analogues or alemtuzumab, due to the high risk of infection, various viral indicators must be closely monitored, especially for CLL patients using alemtuzumab due to the high risk of CMV infection, so it is recommended to test the CMV viral load at least every 2 to 3 Other prophylactic measures include the use of acyclovir or analogues for herpesvirus prevention and sulfonamides for Pneumocystis carinii infection; for CLL patients using anti-CD20 monoclonal antibodies, prophylactic anti-HBV therapy is required if HBV DNA (+) and/or HBsAg (+) is present. HBV therapy (some guidelines recommend that HBcAb positivity alone also requires prophylactic therapy); (3) recommend annual influenza vaccination for CLL patients (within 9 months after rituximab administration, which is not effective because B cells have not recovered) and pneumococcal vaccination every 5 years, avoiding all live vaccines; (4) recommend irradiation of all transfused blood products to prevent transfusion-associated graft-versus-host disease (TA-GVHD); (5) If autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (ITP), and pure red reoccurrence (PRCA) and other autoimmune hemocytopenias occur, comprehensive bone marrow and other tests are required to confirm the disease diagnosis, and treatment is recommended with glucocorticoids, rituximab, intravenous Treatment with glucocorticoids, rituximab, intravenous gammaglobulin, cyclosporine A, splenectomy, etc., and treatment with Eltrombopag film-coated tablets (Eltrombopag) and Romiplostim (Romiplostim) are also recommended for ITP patients. Among them, if confirmed to be fludarabine treatment-related AIHA need to immediately stop fludarabine treatment and no subsequent use; (6) for CLL patients with high tumor load may develop tumor lysis syndrome (TLS), for TLS prevention is more important than treatment, preventive measures include fractionated administration of therapeutic drugs, adequate hydration and alkalinization to avoid serious electrolyte disturbance and renal impairment; ( (7) treatment reactions related to lalidomide, several studies have shown that lymph node enlargement, pain and rash will occur in the early stage of lalidomide use, which is called Tumor Flare, and during the use of lalidomide, it also increases the risk of thrombosis in patients, so it needs to be paid attention to. The former can be treated with hormones and antihistamines, while treatment-related thrombosis can be prevented with aspirin if the patient’s platelet count is >50×109/L. Efficacy assessment and follow-up Most current guidelines for the evaluation of CLL follow the recommendations of the iwCLL 2008 guidelines, which are based on a comprehensive assessment of the patient’s physical examination, hematology, bone marrow examination, and imaging at the end of treatment. Although there are no guidelines recommending the use of sensitive assays such as flow cytometry and quantitative PCR as indicators of efficacy assessment and monitoring of microscopic residual disease (MRD) in patients with CLL, there are a growing number of studies suggesting that patients with CLL who achieve profound remission (MRD-negative) have a better prognosis. For non-high-risk CLL patients who achieve disease remission after induction therapy can enter the follow-up phase, regular routine blood tests and comprehensive physical examinations are recommended for patients, while regular follow-up with imaging examinations such as enhanced CT is not recommended. Conclusion With the improvement of diagnostic technology and the change of national lifestyle, the number of newly diagnosed CLL patients in China is increasing year by year, and the lack of understanding of CLL disease by clinicians in China in the past has led to irregularities in the clinical treatment process. Due to the heterogeneity of CLL disease, it is especially important to accurately determine the condition of each patient and make treatment choices. Therefore, an in-depth understanding and interpretation of the authoritative CLL guidelines will help clinicians in China to make more accurate diagnosis and individualized treatment of CLL patients, and improve the diagnosis and treatment of CLL in China.