1. Etiology of diffuse large B-cell lymphoma.
(1) Congenital or acquired immune dysfunction.
(2) Infectious factors: EBV, human T-cell lymphoma virus type I (HTLV-1), human herpesvirus 8 (HHV-8), bacterial infections such as HP virus infection, chlamydial infections such as Chlamydia psittaci infection.
(3) Genetic factors.
2. Clinical manifestations.
(1) Superficial lymph node enlargement or extra-nodal tissue or organ invasion.
(2) Systemic symptoms: fever, night sweats, decreased physical strength, skin itching and other systemic symptoms before or at the same time of lymph node enlargement. Persistent fever, night sweats and decreased physical strength indicate disease progression and immune failure of the body, and therefore the prognosis is poor.
(3) Anemia: Anemia is secondary to bone marrow invasion, hemolysis and splenic hyperfunction. Progressive anemia and accelerated blood sedimentation are important clinical indicators for determining the development of lymphoma, and are both poor prognostic factors.
3.AJCC stage
Stage I: Invasion of a single lymph node area (I); local invasion of a single extra-nodal organ or site without any lymph node invasion (IE)
Stage II: Invasion of two or more lymph node areas ipsilateral to the transverse septum (II); limited invasion of a single extra-nodal organ or site ipsilateral to the transverse septum with regional lymph node invasion, with or without invasion of other lymph node areas (IIE). The number of invaded areas may be indicated by footnotes.
Stage III: Invasion of lymph node areas on both sides of the septum (III); may be accompanied by extra-nodal invasion of the adjacent lymph nodes (IIE), or by invasion of the spleen (IIIS), or by both (IIIE,S)
Stage IV: diffuse or disseminated invasion of one or more extra-nodal lymph node organs with or without associated lymph node invasion; isolated extra-nodal lymph node organ invasion without adjacent regional lymph node invasion, but with distant site invasion; any invasion of the liver or bone marrow, or node-like invasion of the lung.
4. International Prognostic Indicators (IPI)
All patients International indicators All patients
Age > 60 years; low risk 0-1
Serum LDH greater than 1 times normal; low/intermediate risk 2
Physical status score 2-4; medium/high risk 3
Stage III, IV; high risk 4-5
Extra nodal involvement site greater than 1.
5. Age-corrected International Prognostic Indicators (aaIPI)
Patient ≤ 60 years International index Patient ≤ 60 years
Stage III, IV; low-risk 0
Serum LDH > 1 times the normal value; low/medium risk 1
Physical status score 2-4; medium/high risk 2
High risk 3
6. Compulsory diagnostic tests.
(1) Hematopathological examination of all sections of paraffin blocks of at least one tumor tissue is required. If the sample tissue is not considered conclusive, a new biopsy is required.
(2) Fine needle aspiration (FNA) is not appropriate for the initial diagnosis of lymph nodes. However, when lymph nodes cannot be biopsied by excision or resection, fine needle aspiration tissue examination and flow cytology may provide sufficient information for diagnosis.
(3) Immunophenotypic indicators for confirming the diagnosis: paraffin immunohistochemistry sections CD20, CD3, CD5, CD10, bcl-6, bcl-2, KI-67, MUM1. flow cytology analysis of cell surface markers: CD45, CD20, CD3, CD5, CD10 , CD19. typical immunophenotypes: CD20+, CD45+, CD3-. Among them, CD10 , bcl-6, MUM1 help to distinguish the diagnosis of both subtypes of germinal center (GCB) and non-germinal center (non- GCB ) cell sources. CD10 (+) or (-), bcl-6 (+), MUM1 (-) are GCB, which has a significantly better prognosis than non- GCB.
Diffuse large B-cell lymphoma is a systemic disease, once the diagnosis is confirmed by pathology, systemic systemic examination should be done. These examinations can understand the degree and scope of deep invasion, which can provide accurate basis for clarifying clinical stage, formulating treatment plan, judging prognosis and observing clinical efficacy.
7.Compulsory examination items
(1) Physical examination: pay attention to the area with lymph nodes, including Wechsler’s ring, as well as the size of the liver and spleen.
(2)Evaluation of physical condition.
(3) B symptoms include.
(1) Fever: Unexplained fever with a body temperature over 38°C;
(2) night sweats: profuse sweating that requires changing of bed sheets or covers.
(3) Physical strength loss: unexplained weight loss of more than 10% of usual body weight in the 6 months prior to diagnosis.
(4) Routine check of complete blood count: white blood cell classification, platelet count.
(5) Routinely check LDH, if it is elevated, the prognosis is poor.
(6) Routinely check biochemical complete set.
(7) Routine CT+enhancement of chest, abdomen and pelvis.
(8) Routine bone marrow biopsy for bone marrow invasion.
(9) Routine cardiac ultrasound to determine cardiac ejection fraction.
(10) Routinely check beta-2 microglobulin.
(11) Routinely check EB antibodies if the lesion is in the head and neck area.
(12) Routinely check hepatitis B test, such as hepatitis B positive, it is not recommended to use rituximab immediately, otherwise it will cause liver necrosis; CHOP regimen before chemotherapy need to check the DNA ploidy, such as DNA ploidy: 0.48 + 4 or more; liver function abnormalities (especially glutamic aminotransferase more than 2 times the normal value), need to apply lamivudine antiviral therapy before chemotherapy, at the same time should pay attention to strengthen liver protection therapy and prednisone The application of measurement.
8. Tests that can help in diagnosis in some cases
(1) CT of the head and neck should be performed if there is head and neck invasion.
(2) CT or MRI if brain or spine invasion is suspected.
(3) Bone scan in case of bone pain.
(4) Gastroscopy and colonoscopy if there is gastrointestinal invasion.
(5) CT or MRI of the area if there is extra nodal invasion
(6) Calculate the international prognostic index (IPI): the larger the value, the worse the prognosis.
(7) Pregnancy testing for women of childbearing age
(8) Discuss fertility issues and sperm storage.
(9) Lumbar puncture is required if cumulative sinus, testicular, parietal, periorbital, CNS, paravertebral, bone marrow, or HIV lymphoma itself is present.
(10) PET-CT scan is preferred if available, which can accurately understand the patient’s whole body condition, so as to clarify the staging and formulate the next treatment plan, as well as determine the efficacy and prognosis. Although diffuse large B-cell lymphoma is more sensitive to treatment, only about 40% of the disease can be cured, so it is especially important to standardize treatment for the first time. The standard of care is a combination of chemoradiotherapy.
9.Treatment
(1) Limited stage means.
Stage I: those with or without accompanying large masses (<10M); Stage II without large masses (those with large masses in Stage II have a prognosis similar to that of Stages III and IV, and are therefore classified as advanced and treated as advanced patients.)
1.For patients with stage I and II without large masses (<10M) and with adverse risk factors (age >60 years; elevated serum LDH; physical status score of 2 or more; stage II), 6-8 cycles of chemotherapy with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) regimen, combined or not with 30-36 GY radiotherapy in the involved lymphatic area are acceptable.
2.In the absence of adverse risk factors and without large masses, 4 cycles of chemotherapy with R-CHOP regimen, combined with 30-36GY radiotherapy in the involved lymphatic area, or 6-8 cycles of chemotherapy with R-CHOP regimen for those with contraindications to radiotherapy.
3.For stage I and II large masses (>10M), 6-8 cycles of chemotherapy with R-CHOP regimen, followed by 30-40GY radiotherapy to the involved lymphatic area.
(2) Late stage refers to: those with large masses in stage II, stage III, IV.
1.For stage II with large mass, 6-8 cycles of chemotherapy with R-CHOP regimen, followed by 30-40GY radiotherapy to the involved lymphatic area.
2.For stage III and IV patients with IPI 0-1, 6-8 cycles of chemotherapy with R-CHOP regimen.
(3) For patients with IPI greater than or equal to 2, it is recommended to participate in clinical studies, including high-dose therapy, and for patients who are not suitable for clinical studies, 6-8 cycles of chemotherapy with the R-CHOP regimen may be given.
(3) Rescuing treatment for patients with advanced disease.
Rescuing regimens include MNE (mesna + isocyclophosphamide + mitoxantrone + etoposide), DHAP (dexamethasone + cisplatin + cytarabine) ESDHAP (etoposide + methylprednisolone + cytarabine + cisplatin), and gemcitabine-containing regimens.
Those who have not received prior rituximab-containing therapy may be treated with rituximab-containing combination chemotherapy regimens and given high-dose therapy after remission, autologous stem cell transplantation, or enrolled in clinical studies.
10. Note
(1) Immunohistochemistry CD20(+) before applying targeted drug rituximab, such as CD20(-), then rituximab cannot be applied.
(2) Pre-radiotherapy evaluation with review of all positive results. If PET-CT scan is positive, another biopsy should be performed before starting further treatment.
(3) The R-CHOP regimen is preferred among the above treatment options, and the CHOP regimen may also be used for patients who cannot be treated with the targeted drug rituximab.
(4) For diffuse large B-cell lymphoma of the testis, bilateral testicular radiotherapy (30-36 GY) should be administered after the completion of chemotherapy.
(5) For patients who are not amenable to chemotherapy, radiation therapy to the involved area (IFRT) is recommended.
(6) In specific cases, such as sinus, testicular, epidural, and bone marrow involvement, prophylactic treatment of the central nervous system (4-8 intrathecal injections of methotrexate or cytarabine during the treatment period) should be given.
(7) Pay attention to the prevention of tumor lysis syndrome during chemotherapy, observe the PH value of urine, and give alkalinizing urine treatment.