Non-Hodgkin’s lymphoma



OVERVIEW

Definition

Non-Hodgkin lymphoma (NHL) is a collective term for all lymphomas except Hodgkin lymphoma (HL), which is one of the most common malignant tumors of lymphohematopoietic tissues.

According to histopathological changes, lymphomas can be divided into two categories: HL and NHL.

Staging and classification

In the WHO classification, NHL is divided into three major categories based on the origin and properties of tumor cells:

Precursor lymphocyte tumors

That is, precursor B-cell and T-cell tumors, a class of highly aggressive tumors of immature precursor lymphocyte (also known as lymphoblastoid) origin.

The two main types include: B-lymphoblast leukemia/lymphoma (B-ALL) and T-lymphoblast leukemia/lymphoma (T-ALL), both of which have a similar cellular morphology and clinical prognosis.

Mature B-cell tumors

About 85% of NHLs are mature B-cell tumors, and the two most common types are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

DLBCL: are diffusely proliferating large B-cell malignant tumors, a heterogeneous group of aggressive lymphomas that account for 30% to 40% of all NHLs and are the most common type of NHL.

FL: It is a follicle center B-cell occurring lymphoma. The incidence is low in China and other Asian countries, accounting for 5-10% of NHL.

Mature T-cell and NK-cell tumors

Originate from mature T cells, post-thymic T cells, or NK cells.

Mainly include:

Peripheral T-cell lymphoma, nonspecific type.

Angioimmunoblastic T-cell lymphoma.

NK/T-cell lymphoma.

Mycosis fungoides/Sezary syndrome.

[Special reminder] According to the pathological morphology of immune cells, immunophenotypic and genetic features and clinical characteristics, each type of NHL can be further divided into more than ten different pathological subtypes, please consult your clinician for specific typing.

Incidence

Percentage of classification: The distribution of pathological types of lymphoma in China is different from that in Europe and the United States, with NHL accounting for about 90% of the cases, of which the T-cell type accounts for 20% to 25%, and the B-cell type accounts for about 80%.

The NHL with the highest incidence of adult lymphoma in China is DLBCL.

In children and adolescents it is acute lymphoblastic leukemia/lymphoma, Burkitt’s lymphoma and interstitial large cell lymphoma.

The main extranodal lymphomas are mucosa-associated lymphoid tissue lymphoma and nasal-type NK/T-cell lymphoma.

Site of origin: 2/3 originated in lymph nodes, 1/3 originated in organs or tissues outside lymph nodes, such as digestive tract, respiratory tract, skin, salivary glands, thyroid gland and central nervous system.

Causes

Causes

The etiology and pathogenesis of NHL have not been fully elucidated, and may be related to a variety of factors as listed below.

Infections

Infections from pathogens may increase the risk of developing NHL, common pathogens include:

EBV

Research suggests that EBV is the cause of Burkitt’s lymphoma.EBV is also strongly associated with T-cell lymphoma and immunodeficiency-related lymphoma.

Retroviruses

Human T-cell leukemia/lymphoma virus (HTLV) has been shown to be the cause of adult T-cell leukemia/lymphoma.

Another retrovirus, HTLV-II, has recently been implicated in the development of T-cell cutaneous lymphoma (mycosis fungoides).

The risk of developing NHL in HIV-infected individuals is 60 to 100 times higher than in the general population.

HHV-8

Human herpesvirus-8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus, is a pro-lymphotropic DNA virus that has been associated with a less common type of NHL, characteristic body cavity lymphoma/primary exudative lymphoma.

Helicobacter pylori.

Gastric mucosal lymphoma is a B-cell mucosa-associated lymphoid tissue (MALT) lymphoma, the presence of Helicobacter pylori antigen is strongly associated with its development, and anti-Helicobacter pylori therapy improves its condition; Helicobacter pylori may be the cause of this type of lymphoma.

Immunocompromised

The patient’s immunocompromise is related to the development of lymphoma.

Lymphoma is more common in patients with hereditary or acquired immunodeficiency than in normal people, and 1/3 of the malignant tumors occurring in patients with long-term application of immunosuppressants after organ transplantation are lymphomas.

The incidence of lymphoma is higher in patients with dry syndrome than in the general population.

Lymphoma in patients with immunodeficiency is mostly related to EBV infection.

Environmental factors and occupational exposure

Such as the use of insecticides, herbicides, fungicides, etc., as well as long-term exposure to solvents, leather, dyes and radiation are associated with the development of NHL.

Genetic factors

NHL is also associated with clustering of family members. Siblings and first-degree relatives of patients with lymphoma or other hematologic tumors have a mildly elevated risk of developing NHL.

Pathogenesis

The pathogenesis of NHL is unknown and may be the result of a combination of internal and external environmental factors.

Symptoms

Common Symptoms

Enlarged lymph nodes

Lymph node enlargement is the most common first clinical manifestation, especially painless progressive enlargement of cervical and supraclavicular lymph nodes, followed by axillary and inguinal lymph nodes.

Low-grade malignant lymphoma: lymph node enlargement is mostly scattered, non-adherent, easily movable multiple lymph nodes.

Aggressive or highly aggressive lymphoma: in the case of rapid progression, the lymph nodes tend to be fused into clusters, sometimes adherent to the basement and skin, and may show local soft tissue infiltration, compression, and edema.

Localized compression symptoms

Enlarged lymph nodes may compress neighboring organs and cause corresponding symptoms.

Mediastinal and hilar lymph node mass may cause chest tightness, chest pain, dyspnea, superior vena cava compression syndrome.

Intra-abdominal masses may cause abdominal pain, abdominal mass, intestinal obstruction, ureteral obstruction, pyelonephrosis, etc.

Symptoms of extra-nodal involvement of lymph nodes

NHL is seldom confined to the lymph nodes, and it is common to see involvement of organs outside the lymph nodes, resulting in a range of symptoms.

Pharyngeal lymphatic ring

Pharyngeal lymphatic ring lesions account for 10% to 15% of NHL. The most common sites are the soft palate and tonsils, followed by the nasal cavity and sinuses.

The main symptoms are dysphagia, nasal congestion, rhinorrhea and large submandibular lymph nodes.

Chest

The chest is most commonly involved in the hilum and mediastinum, and half have pulmonary infiltrates or pleural effusion.

The main symptoms are chest pain, dyspnea and dry cough.

Gastrointestinal tract

NHL involves the gastrointestinal tract more than the small intestine, more than half of which is the ileum, followed by the stomach, and the colon is rarely involved.

The main symptoms include abdominal pain, diarrhea and abdominal masses, and even intestinal obstruction or massive bleeding.

Bone

Bone damage is most common in the thoracic and lumbar spine, followed by the femur, ribs, pelvis and skull.

The main symptom is bone pain at the site of damage.

Skin

Skin involvement manifests as lumps, subcutaneous nodules, infiltrative plaques, ulcers and so on.

Systemic symptoms

There are mainly systemic symptoms such as fever, lethargy, night sweats, etc., which are mostly seen in the late stage.

Itching of the skin, but generalized itching is rare.

Consultation

Department of Medicine

Department of Hematology

If there are unexplained fever, night sweats, weight loss, fatigue and other manifestations, or the appearance of painless progressive enlargement of the swelling, you should consult a doctor promptly.

Department of Oncology

If the patient is diagnosed with this disease, he/she can go to the Department of Oncology or Medical Oncology.

Preparation for medical treatment

Consultation: Registration, Preparation of Information, Frequently Asked Questions

Tips for medical treatment

Wear loose fitting clothes to make it easier for the doctor to conduct the examination.

Large medical institutions usually have consultation centers, so those who cannot confirm the diagnosis or have doubts can be consulted first.

The disease has no specific symptoms in the early stage and can be easily overlooked. Therefore, those with a family history of lymphoma should undergo regular medical checkups for cancer prevention.

Preparation Checklist for Medical Consultation

Symptom list

Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.

Are there painless lymph node enlargement or localized lumps?

Any unexplained persistent fever?

Any recent localized or generalized itching of the skin?

Any recent unexplained weight loss or fatigue?

Medical History Checklist

Is there any family history of lymphoma or other malignant tumors?

Any history of radiation therapy?

Any history of infection with EBV, Helicobacter pylori (Hp), etc.?

Any drug or food allergies?

Checklist

Test results in the last six months, which can be brought to the doctor’s office.

Specialized tests: Tumor markers, blood tests (routine blood tests, blood smears, etc.), bone marrow tests

Pathologic examination: lymph node biopsy pathology.

Imaging examination: ultrasound, CT, magnetic resonance imaging (MRI), PET-CT and other imaging examinations.

Other tests: blood biochemistry tests, etc.

Diagnosis

Diagnosis is based on

Medical history

The patient may have the following medical history:

History of pathogenic infections such as EBV, H. pylori infection, etc.

Family history of hematologic malignancies.

Immunocompromised.

Long-term occupational exposure to solvents, leather, dyes, and radiation that have been associated with the development of NHL.

Clinical manifestations

Patients may have several clinical manifestations as described below:

Most are painless progressive enlargement of cervical or supraclavicular lymph nodes (60% to 70% of cases), followed (about 30%) by axillary lymph node enlargement.

The enlarged lymph nodes may be mobile or adherent to each other, fusing into a mass with a cartilaginous sensation on palpation.

There may be masses on the skin, chest and abdomen.

There may be enlargement of the liver and spleen.

Bone pressure may be present.

There are systemic symptoms such as fever, lethargy, and night sweats.

Laboratory Tests

Blood and bone marrow tests

Supportive Diagnosis: NHL white blood cell counts are mostly normal, and lymphocyte counts may be increased, decreased, or normal.

Determination of disease progression: In advanced stage complicating acute lymphoma cell leukemia, leukemia-like blood and bone marrow picture may be presented.

Laboratory tests

To determine prognosis: elevated serum lactate dehydrogenase suggests a poor prognosis.

To determine disease progression: when serum alkaline phosphatase activity or blood calcium is increased, it suggests skeletal involvement.

Secondary diagnosis: B-cell NHL may be complicated by hemolytic anemia with a positive or negative anti-human globulin test and, in rare cases, monoclonal IgA or IgM.

Imaging

Commonly used imaging methods: computed tomography (CT), magnetic resonance imaging (MRI), positron emission computed tomography (PET-CT), ultrasound and endoscopy.

CT examination

CT is currently the most commonly used imaging tool in lymphoma patients.

It can be used as the most common imaging method for lymphoma staging, restaging, efficacy evaluation and follow-up. For patients without contraindications to iodine contrast, enhanced CT scans should be used whenever possible.

Generally all NHL patients need to have CT of the neck, chest, abdomen, pelvis and other relevant areas before, during and after treatment.

CT can clearly show the size and density of the lymph nodes in each area, their relationship with the surrounding blood vessels and organs, and can also show extra-nodal lesions.

MRI examination

MRI should be preferred for lesions in the central nervous system, bone marrow and muscle areas.

MRI can be chosen or preferred for parenchymal organ lesions such as liver, spleen, kidney, uterus, etc., especially for those who are not suitable for enhanced CT scanning, or as a further examination after suspected lesions are detected by CT.

PET-CT examination

PET-CT is currently the best examination method for the staging and restaging of lymphoma, evaluation of therapeutic efficacy and prognosis prediction, except for inert lymphoma.

PET-CT is costly and is recommended for the following conditions when available:

It can be used as a routine test for pre-treatment staging as well as re-staging of NHL subtypes with high fluorodeoxyglucose (FDG) affinity.

For most DLBCL, a bone marrow biopsy is not necessary if PET-CT suggests definite bone marrow involvement.

It can be used as a basis for biopsy site selection in the transformation of inert lymphoma to a more aggressive pathologic type.

PET-CT is better than other methods for efficacy and prognosis prediction and can be used selectively.

Ultrasound

It can be used for the diagnosis and review of superficial lymph nodes and superficial organ (e.g., testis, thyroid, breast, etc.) lesions, but is generally not used for the staging diagnosis of lymphoma.

It can be used selectively for abdominal and pelvic lymph node examination.

For the evaluation of abdominal and pelvic substantial organs such as liver, spleen, kidney, uterus, etc., it can be used as a supplement to CT and MRI, especially when enhanced CT scanning cannot be performed.

In superficial lymph node dissection biopsy, selective ultrasound detection of sonographically abnormal lymph nodes can help improve the accuracy of the biopsy.

Ultrasound-guided puncture biopsy is also used in the diagnosis of lesions in the deep lymph nodes, liver, and mediastinum.

Isotope bone scan

Bone scan is better than CT for follow-up observation and prognosis assessment after treatment of primary bone lymphoma.

Gastrointestinal barium angiography

Gastrointestinal barium contrast is a commonly used method to diagnose gastrointestinal NHL.

Gastric NHL: the gastric mucosa shows “cobblestone-like” changes, the lesions are mainly located in the submucosa, and gastric peristalsis still exists when the lesions are extensive. This feature is the main basis for distinguishing gastric NHL from gastric cancer.

NHL of the small intestine: scattered scattered well-defined filling defects in the small intestine, or coexistence of stenosis and dilatation of the intestinal lumen.

Colorectal NHL: It is more common in the rectum and cecum, and is characterized by nodular or mass filling defects and narrowing and thickening of the intestinal wall.

Pathologic examination

Pathologic examination is the mainstay of NHL diagnosis.

Methods of obtaining specimens

Resection of lymph node lesions

Intact lymph nodes should be removed whenever possible.

If the lymph node lesions are superficial, cervical, supraclavicular and axillary lymph nodes should be selected whenever possible.

Hollow-core needle aspiration

Use only in patients in whom resection or excision of diseased tissue cannot be obtained effectively and safely.

In recurrent patients, if resected or excised tissue specimens cannot be obtained, pathological diagnosis can be made from lesions obtained by hollow-core needle aspiration.

Diagnostic methods

The pathologic diagnosis of NHL requires a combination of morphology, immunohistochemistry (IHC), genetic and molecular biology techniques, and flow cytometry, and no single method can be defined as the “gold standard.

Morphology: Very important in the pathologic diagnosis of NHL. Different types have characteristic and diagnostic morphological features.

Immunohistochemistry.

Can be used to identify the immunophenotype of lymphoma cells, such as B or T/NK cells, differentiation and maturation of tumor cells.

Differential diagnosis of different pathologic subtypes is performed by combining relevant immunohistochemical markers.

Fluorescence in situ hybridization (FISH) detection technology

It can detect specific chromosome breaks, translocations or amplifications, etc., which is of guiding significance for the auxiliary diagnosis of lymphomas associated with specific chromosomal abnormalities.

For example, t(8;14) translocation associated with Burkitt’s lymphoma and t(14;18) translocation associated with follicular lymphoma.

Lymphocyte antigen receptor gene rearrangement detection technology

Monoclonal rearrangements of lymphocyte receptor genes are a major feature of lymphoma cells.

It can be used to assist in identifying the monoclonal versus polyclonal nature of lymphocyte proliferation, as well as lymphomas that cannot be diagnosed by IHC, and is an important complement to morphological and IHC tests.

Others: These include in situ hybridization, second generation sequencing (NGS), and flow cytometry, which are useful complements to conventional pathologic diagnostic methods.

Staging

Correct staging is important for judging prognosis and selecting treatment.

Ann-Arbor staging is the current universal staging system to describe NHL.

The Ann-Arbor (revised by Cotswolds) staging system is as follows:

Staging

Stage I: invasion of one lymph node area (I), or invasion of a single extra-lymph node organ or site (IE).

Stage II: invasion of two or more lymph node areas on one side of the diaphragm (II) or plus limited invasion of a single extra-nodal organ or site (IIE).

Stage III: invaded lymph node areas on both sides of the diaphragm (III) or plus limited invasion of one extranodal organ or site (IIIE) or the spleen (IIIS) or both (IIIES).

Stage IV: diffuse or disseminated invasion of one or more extranodal organs with or without lymph node invasion.

Recording symbols

The following symbols may be used to record the site of involvement:

E: Extranodal, lymphoma involving organs outside the lymph nodes.

When a single extranodal site is involved and the lesion invades an organ/tissue that is directly connected to a lymph node/lymphoid tissue, it is not recorded as stage IV.

The letter “E” should be entered after each stage (e.g., if the lesion infiltrates into the skin connected to the left cervical lymph node, it is recorded as “IE”).

X: Large mass, tumor diameter > 1/3 of chest width or fusion mass > 7.5 cm in diameter.

Others: M (bone marrow), S (spleen), H (liver), O (bone), D (skin), P (pleura), L (lung).

Grouping

Each stage can be subdivided into Group A and Group B according to the presence or absence of systemic symptoms.

Group A: no systemic symptoms.

Group B: Systemic symptoms, including unexplained fever (>38°C for 3 consecutive days or more), night sweats (e.g., profuse sweating during sleep requiring change of bed sheets or covers for 7 consecutive days or more), or weight loss (loss of 10% or more within 6 months with no other explainable cause).

Special Reminder.

It is difficult to apply Ann-Arbor staging to certain NHLs with extranodal lymph node origin, such as chronic lymphocytic leukemia, cutaneous T-cell lymphoma, primary extranodal nasal-type NK/T-cell lymphoma, and primary gastric, intestinal, and central nervous system lymphomas.

These NHLs, which originate in specific extranodal organs and sites, usually have their own staging system.

Detailed consultation with the physician is recommended for specific staging.

Differential Diagnosis

In addition to the need to differentiate the various subtypes of NHL from each other, Hodgkin’s lymphoma also needs to be differentiated from non-lymphoma diseases.

Lymphoma is a systemic disease and therefore needs to be differentiated from many diseases, especially those that occur outside of the lymph nodes, and from diseases at the corresponding sites.

The final diagnosis of most lymphomas requires pathology to be determined, and some may require molecular testing for final characterization.

Hodgkin’s Lymphoma

The differentiation of Hodgkin’s lymphoma from non-Hodgkin’s lymphoma relies primarily on pathologic testing. In general, Hodgkin’s lymphoma can be found in lymph nodes or extra-nodal tissues such as bone marrow, lungs, or skeletal tissues, where R-S cells can be found.

In addition, Hodgkin’s lymphoma is often confined to a specific group of lymph nodes and infrequently involves extranodal sites, whereas non-Hodgkin’s lymphoma often spreads to more than one group of lymph nodes and often involves extranodal sites.

Enlargement of superficial lymph nodes

Acute lymphadenitis

Generally, there are obvious redness, swelling, heat and pain locally, which are often painful and confined lymph node enlargement, the skin may be flushed, the texture is soft to moderately hard, there is spontaneous pain and pressure pain, the surface is smooth, without adhesion, the enlargement will stop to a certain extent, and it is related to the location of the primary lesion.

In patients with non-Hodgkin’s lymphoma, the symptoms of superficial lymph node enlargement will progressively worsen and are usually painless.

Chronic lymphadenitis

Commonly, scattered lymph nodes are enlarged in the lateral neck or submandibular region, about the size of green beans to fava beans, flat, medium-soft, smooth surface, and movable. There may be light or no pressure pain.

If it is difficult to make a clear diagnosis for a while, antibiotic treatment can be tried, and if the lumps shrink significantly, lymphadenitis is more likely.

If necessary, needle aspiration cytology examination can be done, chronic inflammatory cells can be seen, and lymph node biopsy can confirm the diagnosis.

Lymph node metastatic cancer

When lymph node metastasis occurs in cancer, it can also lead to enlarged lymph nodes. For example, breast cancer often has enlarged lymph nodes in the axilla of the same side.

However, patients usually have clinical manifestations of primary tumor lesions, and lymph node biopsy can help to identify them.

Diseases causing prolonged fever

Lymphoma with fever as the main manifestation needs to be differentiated from tuberculosis, sepsis, connective tissue disease, necrotizing lymphadenitis and hemophagocytic lymphohistiocytosis.

Generally, it needs to be judged together with medical history and relevant examination results, and pathological diagnosis is needed to confirm the diagnosis if necessary.

Extranodal lymphoma

Lymphoma of non-lymph nodes needs to be differentiated from other malignant tumors of corresponding organs or sites. Pathologic diagnosis is usually required to confirm the diagnosis.

For example, MALT lymphoma and DLBCL need to be differentiated from gastric cancer and gastrointestinal mesenchymal tumor.

Treatment

Principles of treatment

At present, NHL is mainly treated with comprehensive treatment including internal medicine, radiotherapy and surgery. Among them, internal medicine treatments include chemotherapy, targeted therapy, and bioimmunotherapy.

The goal of treatment is to maximize clinical cure or long-term progression-free survival of the disease and maximize the improvement of patients’ quality of life.

Therapeutic means

According to the patient’s age, physical condition, lymphoma subtype, lesion site, stage and other factors, standardized, comprehensive and individualized treatment is the key to obtaining a good therapeutic effect under the premise of following the guidelines and treatment principles.

Chemotherapy

Chemotherapy, or chemotherapy for short, is a treatment method that uses chemically synthesized drugs to kill tumor cells and inhibit their growth.

Chemotherapy is the main treatment for non-Hodgkin’s lymphoma. Multi-drug combination chemotherapy program is mostly used.

According to the characteristics of lymphoma cell growth cycle, the combination of cell cycle specific and cell cycle non-specific drugs are used.

Commonly used chemotherapy drugs for lymphoma

Anthracyclines: doxorubicin, epirubicin, etc.

Alkylating agents: cyclophosphamide, isocyclophosphamide, etc.

Dihydrofolate reductase inhibitors: methotrexate, etc.

Antibiotics: bleomycin, etc.

Plant-based drugs: etoposide, vincristine, etc.

Note: Adequate intensity and duration of drug dosage are essential to achieve satisfactory efficacy.

Commonly used chemotherapy regimens

CHOP regimen: cyclophosphamide + doxorubicin + vincristine + prednisone. It is the standard treatment regimen for aggressive NHL.

R-CHOP regimen: i.e. CHOP regimen with rituximab before chemotherapy.

DHAP regimen: dexamethasone + high-dose cytarabine + cisplatin. Commonly used in second-line treatment.

Special Reminder

Drug treatment, especially chemotherapy, is recommended to choose the appropriate program under the guidance of the doctor, do not self-medication.

Radiotherapy

Tumor radiation therapy, referred to as radiotherapy, is a local treatment that can be used to eradicate and eliminate local primary tumors or metastatic lesions, and can treat tumors alone.

Lymphoma is one of the most common radiosensitive tumors, and radiotherapy plays an important role in local control, consolidation and palliative reduction of lymphoma.

Role of radiotherapy in lymphoma treatment

Radical effect: For certain early stage lymphomas, radiotherapy alone can achieve radical effect.

Consolidation: For some aggressive lymphomas, adding radiotherapy on top of chemotherapy can further consolidate the treatment effect.

Reducing symptoms: for patients with poor tolerance to chemotherapy, especially those who have received too many courses of chemotherapy in the past or elderly patients. Radiotherapy can reduce local symptoms, slow down disease progression, prolong survival time and improve quality of life.

Rescue treatment: for the spinal cord compression and gastrointestinal obstruction caused by certain lymphoma, local radiotherapy can rapidly release or reduce the compression, relieve the symptoms, and finally achieve the effect of rescue treatment.

Adverse reaction of radiotherapy

Acute toxic reactions caused by radiotherapy: mucosal reactions (ulceration, leukoplakia, pain, etc.), gastrointestinal reactions (nausea, lack of appetite, vomiting) and bone marrow suppression.

Post-radiotherapy complications: radiation pneumonitis, pericarditis, myelitis, hypothyroidism, etc.

In children and adolescents, special attention also needs to be paid to the fact that radiotherapy may affect bone development.

Patients who have undergone expanded field high-dose irradiation have an increased likelihood of developing a second tumor in the radiotherapy field and need to be followed up closely at regular intervals.

Hematopoietic stem cell transplantation (HSCT)

HSCT involves the intravenous infusion of normal human hematopoietic stem cells into patients who have undergone pretreatment (chemotherapy/radiotherapy) to rebuild the patient’s hematopoietic and immune functions for the purpose of treating certain diseases.

Classification

HSCT is classified according to the source of hematopoietic stem cells: bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT).

According to donor genetics, it can be classified into autologous hematopoietic stem cell transplantation (AHSCT), homozygous HSCT between identical twins, and allogeneic HSCT.

Allogeneic HSCT

In the following cases, autologous or allogeneic HSCT may be attempted after high-dose combination chemotherapy with the aim of maximizing tumor cell killing and achieving longer-term remission and disease-free survival.

Age under 55 years;

Normal function of vital organs;

Short remission period;

Aggressive lymphoma that is refractory and prone to relapse;

Those who can achieve more than 3/4 lymph node shrinkage with 4 CHOP regimens.

Autologous peripheral blood HSCT

When autologous peripheral blood HSCT is used for lymphoma treatment, there is less chance of graft contamination by lymphoma cells, faster recovery of hematopoietic function, and is indicated for patients with bone marrow involvement or after pelvic irradiation.

Surgical treatment

As a systemic hematologic malignancy, surgical resection of non-Hodgkin’s lymphoma is mostly not used as a routine treatment.

Surgical intervention is still required in some special cases, mainly including:

For enlarged lymph nodes or suspected invading organs to perform surgical excision (or resection) biopsy, in order to clarify the pathologic diagnosis.

For early primary gastrointestinal lymphoma, surgical resection can be given followed by chemoradiotherapy for consolidation.

For the complications such as spinal cord compression syndrome and cavity organ obstruction caused by lymphoma compression, decompensated surgery is feasible.

For those with hypersplenism, splenectomy can be performed if there is an indication for splenectomy, so as to improve the blood image and create favorable conditions for future chemotherapy.

Biological therapy

Monoclonal antibody

Most of NHL is B-cell, 90% express CD20.

Application: All CD20-positive B-cell lymphomas can be treated with CD20 monoclonal antibody (e.g. rituximab).

Improve chemotherapeutic efficacy: Applied before each cycle of chemotherapy, it can significantly improve the complete remission rate and disease-free survival time of inert or aggressive B-cell lymphoma.

Improvement of transplantation outcome: in vivo purification of B-cell lymphoma with rituximab prior to HSCT may improve the efficacy of transplantation therapy.

Interferon.

Interferon has antiviral and antitumor activity and immunomodulatory effects.

It has a partial palliative effect on mycosis fungoides, etc.

Anti-Hp drugs

Gastric MALT lymphoma is treated with anti-Hp therapy in some patients with improvement of symptoms and disappearance of lymphoma.

CAR-T therapy

CAR-T (chimeric antigen receptor T-cell) cellular immunotherapy, i.e. chimeric antigen receptor T-cell immunotherapy, is effective in the treatment of refractory/recurrent B-cell lymphoma.

Treatment of common NHL

The treatment of NHL is closely related to the pathologic subtype, and only a brief description of the treatment strategy is given here. For specific treatment directions, please refer to the terminology related to the pathologic subtypes of lymphoma.

Inert Lymphoma

Inert lymphomas develop slowly and are effectively treated with chemotherapy and radiation, but do not resolve easily.

Common subtypes

B-cell inert lymphoma: includes small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, and FL.

T-cell inert lymphoma: refers to mycosis fungoides/Sezary syndrome.

Staging

Stage I and II

Survival after radiation or chemotherapy can be up to 10 years, and some patients have spontaneous tumor regression, so the palliative care principle of watch and wait is advocated.

If the disease progresses, oral monotherapy with nitrogen mustard phenylbutyrate or cyclophosphamide can be used.

Stage III and IV

The median survival time after chemotherapy can be up to 10 years, although there will be many relapses, and the combination chemotherapy can be used with COP regimen or CHOP regimen.

FC (fludarabine, cyclophosphamide) regimen can be tried for those whose progression cannot be controlled.

Aggressive lymphoma

Aggressive lymphoma should be mainly treated with chemotherapy regardless of the stage. For those with residual mass after chemotherapy, localized huge mass or central nervous system involvement, local radiotherapy with extended irradiation can be used as a supplement to chemotherapy.

Common subtypes

B-cell aggressive lymphoma: including primitive B lymphocyte lymphoma, primitive immune cell lymphoma, condyloma, DLBCL and Burkitt lymphoma.

T-cell aggressive lymphoma: including primitive T-cell lymphoma, angioimmunoblastic T-cell lymphoma, mesenchymal large cell lymphoma and peripheral T-cell lymphoma, etc.

Treatment regimen

CHOP regimen: cyclophosphamide + doxorubicin + vincristine + prednisone. It is the standard treatment regimen for aggressive NHL.

R-CHOP regimen: i.e. CHOP regimen with rituximab before chemotherapy, which can get better efficacy and is the classic regimen for diffuse large B-cell lymphoma treatment.

Prognosis

Survival

NHL is a heterogeneous group of lymphomas, and the International Prognostic Index (IPI) is now commonly used as a prognostic stratification evaluation for DLBCL.

International Prognostic Index (IPI)

ECOG (Eastern Cooperative Oncology Group) score

III or IV

Number of extra-nodal invasion sites＜2≥2

Number of extranodal invasion sites

＜2

≥2

Normal elevation of lactate dehydrogenase (LDH)

Lactate dehydrogenase (LDH)

Normal

Elevated

Risk Grouping and Survival

Risk Grouping Number of IPIs 2-year survival 5-year survival

Low risk 0 or 184% 73%

Low risk

0 or 1

84 percent

73%

Low-moderate risk 266% 50%

Low-Medium Risk

2

66% 50%

50%

High-Medium Risk 354% 43

High-Medium Risk

3

54% High-Medium Risk

43 percent

High-risk 4 or 534% 26%

High-risk

4 or 5

34% 26

26%

Special Reminder

The overall survival time of cancer patients can be roughly predicted by the 5-year survival rate, which refers to the proportion of patients whose tumors survive for more than 5 years after various comprehensive treatments.

The probability of recurrence after 5 years is very low and is generally regarded as clinical cure.

Statistics such as 2-year survival rate and 5-year survival rate are only used for clinical research and do not represent the specific survival period of an individual. The individual survival period of a patient needs to be determined by a combination of factors, and it is recommended to consult with the consulting physician.

Prognostic factors

The prognosis of NHL depends on the type of pathology, clinical stage, and a combination of other factors.

The prognosis for different pathological types of lymphoma varies widely.

Daily

Daily management

Mindfulness and Emotional Adjustment

A good mood and mindset cannot be replaced by drugs.

After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death.

Family members should pay attention to listen to the patient’s heart, improve the patient’s mental ability and relieve anxiety symptoms.

Encourage the patient’s family to give support so that the patient can face the surgery and other treatments positively with a good mindset.

During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores that are within their ability, so as to reintegrate into their social roles.

Living

The living environment should be kept clean, with sufficient ventilation, sufficient sunlight and suitable greenhouse temperature. Disinfect the room regularly to avoid infection.

Maintain good hygiene and cleanliness to prevent accidental bodily injury. Rinse your mouth with saline solution and use a soft-bristled toothbrush after meals and before bedtime.

Maintain a positive and optimistic state of mind, reduce tension and anxiety, and avoid excessive activity and trauma for those prone to bleeding. If the lesion is in the lower limbs, try not to get out of bed to avoid fracture.

Dietary regulation

Balanced dietary structure, diversified food types and rich nutrition. Pickled, fried and deep-fried food should be avoided.

Eat more vitamin-rich vegetables and fruits, such as broccoli, tomatoes, celery, lettuce, kiwi, apples and bananas.

Eat more protein-rich foods, such as eggs, milk, lean meat and fish.

It is recommended not to eat foods that stimulate the secretion of stomach acid, such as foods that are too sweet and spicy.

Rest and Exercise

Pay attention to rest, avoid staying up late or straining, and ensure sufficient sleep and rest to reduce physical exertion and promote recovery.

When the condition improves, start with low intensity exercise such as walking and gradually resume normal activities.

Review and Follow-up