Malignant lymphoma is a solid tumor that originates from lymphopoietic tissue and can start in lymph nodes or in extra-lymph node organs. Colorectal malignant lymphoma is an extra-nodal lymphoma and can be divided into primary and secondary. Secondary colorectal malignant lymphoma refers to lymphoma from other sites invading the colorectum and is a manifestation of systemic lymphoma, which is not described here. Primary colorectal malignant lymphoma is a group of lymphomas that originate in the submucosal lymphoreticular tissue of the colorectum, and is classified as primary malignant lymphoma of the gastrointestinal tract.
Primary colorectal malignant lymphoma is characterized by the lack of specific symptoms in early stage, difficulty in preoperative diagnosis and high clinical misdiagnosis rate, but the efficacy and prognosis are better, which is obviously different from other colorectal malignant tumors.
I. Epidemiology and etiology
(I) Epidemiology
PGIML is a non-epithelial malignant tumor that can occur at any age, with a peak age of 50-70 years, a median age of 50-55 years, and a male-to-female sex ratio of 3:1. Although the gastrointestinal tract is the most common site of extra-junctional lymphoma, PGIML is still rare clinically, accounting for only 1%-4% of gastrointestinal tumors and 5%-10% of malignant lymphomas. It is most common in the stomach, accounting for 50%-60%, followed by the small intestine, accounting for 30%-40%, and the ileum and colorectum accounting for 10%.
Malignant lymphomas originating in the colorectum are much less common, accounting for only 0.06% of all colon tumors, 0.1% of all rectal tumors, and 1%-2% of all colorectal malignancies. Primary colorectal malignant lymphoma is more likely to occur in the cecum, where lymphoid tissue is abundant, especially in children, and to a lesser extent in the rectum. In primary colorectal malignant lymphoma, the ileocecal part accounts for 71.5%, rectum accounts for 16.9%, ascending colon accounts for 6.2%, sigmoid colon and anus each accounts for 1.5%, descending colon and appendix each accounts for 0.7%.
(II) Etiology
Recent research evidence suggests that the main causative agent of malignant lymphoma is EBV infection, based on the following.
(i) Patients with lymphoma have almost average titers of antibodies to serum VCA/IgA second only to those with nasopharyngeal carcinoma;
The antibody titers are low in those with low grade malignancy and high in those with B-cell-derived lymphoma, and the antibody titers become negative as the disease improves and stabilizes;
③If the antibody titer continues to decrease, the disease is most likely to deteriorate.
③If the antibody titer continues to decrease, the disease will most likely deteriorate. ④The antibody titer will increase again when there is a relapse;
⑤ Most lymphoma cases are concentrated in the spring and summer rainy seasons, and EBV infection is associated with seasonal humidity.
Other factors involved in the development of lymphoma are.
①Immune depression: When immune function is low, then EBV latent infection (virus survives in quiescence) is transformed into active infection and may induce malignant lymphoma.
②Genetic factors: Some studies have confirmed that lymphocytosis, X chromosome genetic factor deletion, etc., can cause the body to have an incomplete immune defense against EBV and lead to active EBV infection, which in turn induces unlimited proliferation of B lymphocytes. In primary immunocompromised patients, B lymphocytes are particularly reactive to EBV, which is sufficient to induce malignant lymphoma. In addition EBV-associated nasopharyngeal carcinoma is mostly seen in southern Chinese and Burkitt’s lymphoma is mostly seen in the African Roo, both suggesting a correlation between their genetic factors and EBV-induced cancer.
③Environmental factors: It has become a recognized fact that the incidence of malignant lymphoma is high in areas with severe radioactive contamination. It is suggested that radioactive materials make immunity low, causing active EBV infection and malignant lymphoma.
④Poor environmental hygiene and too high population density are conducive to the spread of EBV epidemic and the development of malignant lymphoma.
II. Pathology
(I) Pathological characteristics
Compared with malignant tumors in other tissues of human body, the most significant feature of lymphoma is its diversity or called heterogeneity, which is mainly manifested as follows.
(1) The lymphoid tissue is widely distributed, and lymphoma is also a systemic disease. In addition to lymph nodes, lymphoma can also be seen in various organs and/or tissues throughout the body, which determines the importance of accurate clinical staging.
②There are many types of lymphoma because of the variety of lymphocyte types. Currently, lymphomas are divided into two major categories: Hodgkins disease (HD) and non-Hodgkins lymphoma (NHL). There are 4-6 histological types of HD and more than 20 types of NHL, some of which are low-grade malignant and some of which are highly malignant. There is a great difference in treatment and prognosis.
(3) Lymphocytes are immunologically active cells, and the immune response of the body involves lymphocytes, and the lymphocytes of immune response (activated lymphocytes) are similar to tumorigenic lymphocytes in terms of cell morphology, thus leading to a very difficult differentiation between tumor and non-tumor (lymphoproliferative), resulting in the current situation of high misdiagnosis rate. Currently, the pathological diagnosis of lymphoma is still the most misdiagnosed area among all tumor pathological diagnoses.
(II) Pathological staging
Pathological staging of lymphoma has always been a difficult problem, and an ideal classification has not yet been accepted. Since the 1970s, with the proliferation of monoclonal antibodies to lymphocytes and the application of genetic recombination techniques since the 1980s, the classification of lymphoma has been changed and updated again and again. In foreign countries, many medical centers have their own classification schemes, but in the literature, the working formulation is mainly used in the United States and the Kiel classification is mostly used in Europe.
In China, eight national academic conferences on lymphoma were held in just 10 years, and corresponding classification schemes were developed, among which the Shanghai classification (1982) and Chengdu classification (1985) had some influence, but they were not fully applied to daily work. In April 1993, a total of 19 lymphoma experts from the United States (7), the United Kingdom (3), Germany, Italy (2 each), France, Denmark, Spain, Belgium, and Hong Kong (1 each) met in Berlin and agreed on a new classification scheme called the REAL classification, which is currently being promoted.
WHO published a new classification in 1998, which is basically the same as the REAL classification.
REAL pathological staging of lymphoma
Clinical manifestations and staging
(I) Clinical manifestations
Primary malignant lymphoma of the colorectum lacks characteristic clinical manifestations. Its onset is insidious, and the main clinical manifestations are abdominal pain, significant weight loss and abdominal swelling. The abdominal pain is caused by the compression of the nerve plexus in the colorectal wall by lymphoma infiltration, the abdominal mass is caused by the rapid growth of tumor lymphatic tissue, and the significant weight loss is caused by the rapid growth and consumption of the malignant tumor. Other manifestations include blood in stool due to necrosis and detachment of tissues caused by tumor in the colon, as well as diarrhea, abdominal distension, partial intestinal obstruction, and non-specific symptoms such as intussusception.
(B) Auxiliary examination
1, fiberoptic colonoscopy; fiberoptic colonoscopy is the main method to diagnose the disease, endoscopic positive rate of up to 50%-80%, endoscopic lesion morphological characteristics are mainly manifested in three types.
① diffuse type: the lesion intestinal wall is obviously thickened, hardened, lost normal luster, mucosal folds hypertrophy like cerebral gyrus or irregular morphology, also visible diffuse granular or clustered small nodule-like unevenness, often accompanied by erosion or even shallow ulcers, narrowing of the intestinal lumen, restricted inflation and expansion, the lesion often involves a fairly long section of the intestinal tube;
②Polyp type: polyp-like masses with a broad base, rough and uneven surface, may be accompanied by erosions and shallow ulcers;
③Ulcer type: it can be a large and deep ulcer with malignant features, such as irregular and raised ulcer periphery in the shape of a ring dike, surrounded by giant folds or cerebral gyrus-like mucosal folds, etc.; it can also appear to be a benign multiple ulcer.
There are also shortcomings in the diagnosis of colorectal lymphoma by colonoscopy.
(1) Intestinal lymphoma is usually found in the terminal ileum and ileocecal region, and there is a large blind area in colonoscopy.
②Some patients with colorectal lymphoma have smooth intestinal masses without obvious protrusions and mucosal erosions and necrosis, and enteroscopy shows inflammatory-like changes, which is not easy to confirm the diagnosis.
③ Although intestinal malignant lymphoma has certain histological features such as heterotype of histiocytes and lymphocytes, pathological nuclear division image, and tissue structure destruction, the diagnosis is often not confirmed due to shallow sampling, too small tissue block, and extrusion during tissue clamping. Therefore, the confirmation rate of local biopsy under colonoscopy is low, only about 60%.
2.Ultrasound; ultrasound has high sensitivity for the examination of intestinal lymphoma, and the sonographic performance of lymphoma has certain characteristics, which can provide reference for clinical diagnosis and treatment, and is a better auxiliary examination method. Mass-type intestinal lymphoma has certain characteristics on ultrasound.
①The tumor is large, long oval, and the tumor spreads along the long axis of the intestine.
②Because the lymphoma starts from the lymphoid follicle in the submucosa layer, infiltrates the mucosal layer inward and reaches the muscular layer outward, often causing the mucosal folds to disappear and become flat. The mucosa of the intestinal cavity at the lesion site shows more clearly, and the internal gas is fine-lined and flatter. Compared with adenocarcinoma, lymphoma is less destructive to the mucosa. When a small amount of fluid accumulates in the intestinal lumen, it shows hydronephrosis-like changes. The plasma membrane layer showed smooth and strong light band.
(3) The echogenicity of the mass is lower than that of adenocarcinoma, with a slightly high echogenic light band, and it may show intestinal condyloma-like changes, and there are reports of lymphoma being misdiagnosed as intestinal condyloma.
Non-Hodgkin’s lymphoma is a medullary tumor, so the blood supply is rich, and the ultrasound often reveals abundant long and thick colored blood flow. The study of foreign Pavlick suggests that ultrasound endoscopy is important for estimating the depth of tumor infiltration and distinguishing benign and malignant lymph nodes.
3.X-ray imaging; barium enema examination of colorectal malignant lymphoma may show multiple submucosal bulges, large filling defects or stiff intestinal wall without narrow or slightly narrow intestinal lumen and intact mucosa, which is not easy to confirm the diagnosis.
Dual gas-barium imaging can be shown in four types.
① infiltrative type: lumen wall thickening, lumen slightly narrowed, peristalsis can still pass under fluoroscopy, mucosal folds are thick, tortuous and disorganized (huge folds).
②Mass type: sharply bounded bulging mass with irregular shape and large lesions, mostly up to 5-10 cm in diameter.
③Ulcer type: intraluminal ulceration, manifested as a filling defect in the colorectal lumen with smooth borders, within which there may be irregular niche shadows.
④Polyp type: multiple round translucent shadows, varying in size and resembling pebbles.
The superiority of abdominal CT is that it can not only clearly show the morphology of the lesion of ileocecal lymphoma, but also can clarify the extent of tumor involvement and show the invasion of the surrounding structures and lymph node metastasis that cannot be observed by barium examination.
Morphologic features of lesions on CT are divided into 4 categories.
(1) Multiple nodular type: a limited thickening of the small intestinal wall with a smooth outer wall contour;
(2) intramural infiltrative type: mostly larger intestinal wall thickening.
(3) mesenteric involvement with extraluminal mass: mesenteric lymph nodes are enlarged in a mass-like pattern;
(4) Mass type: clear boundary, smooth plasma membrane surface, lumen is obviously narrowed but not completely obstructed.
5.Immunohistochemistry method; it plays an important role in the diagnosis and cell typing of lymphoma, which helps to differentiate it from reactive lymphocytic hyperplasia, and the common clinical tests include LCA, L26, CEA, IgM, IgG, CD20, CD3, Kappa, Lambda, c-myc, etc.
6.Gene diagnosis of lymphoma; With the development of molecular biology in recent years, research has found that there are many genetic variants in lymphoma, which are meaningful for its diagnosis and detection of small residual lesions.
For example, about 90% of follicular lymphomas have t(14;18)(q32;q21) chromosomal translocations, producing bcl-2 IgH fusion genes, etc. The fusion genes generated by chromosomal translocations reflect the molecular mechanism of lymphoma pathogenesis and have important diagnostic value for some difficult cases and are also target loci for future treatment.
②Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements. Each lymphoma patient has specific gene rearrangement sequences, and the detection of rearrangement sequences by polymerase chain reaction (PCR) is useful for diagnosis in the early stage of the disease, and specific probes can be used to detect small residual lesions in the remission stage, etc. This method can be used not only for clinical diagnosis and staging, but also for subclinical and subpathological diagnosis, and its confirmation rate can reach 87.1%. Although the genetic diagnosis of lymphoma has made great progress in recent years, there are still many problems, and it is still a topic for further research in the future.
(III) Clinical staging
According to the clinical staging scheme developed at the AnnArbor meeting in 1970, extra-nodal lymphoma can be clinically classified into 4 stages, namely stage IE: the lesion invades only a single organ other than lymph nodes. Stage IIE: The lesion is confined to organs other than lymph nodes and more than one regional lymph node on the same side of the diaphragm. Stage IIIE: Involvement of an organ other than lymph nodes plus lymph nodes on both sides of the diaphragm.
Stage IVE: The lesion has invaded multiple lymph nodes and sites other than lymph nodes, such as involvement of the lung, liver and bone marrow. Most scholars now believe that it is more appropriate to stage primary colorectal lymphoma using the Blackledge staging system specific to primary gastrointestinal lymphoma. The specific grading and its comparison with other grading methods are described in Table 28-2.
Lymphoma staging
Chronic cases often present with chronic abdominal pain, diarrhea, prolonged fever, and weight loss, or with an abdominal mass. Acute cases present with severe abdominal pain with a painful abdominal mass, or with diarrhea or blood in the stool. In chronic cases, there is a history of long-term abdominal pain, diarrhea, fever, weight loss, sudden acute intestinal obstruction, peritonitis or massive blood in stool.
IV. Diagnosis and differential diagnosis
(I) Diagnostic criteria
The diagnostic criteria for primary colorectal malignant lymphoma, as suggested by Dawson et al, are.
(1) No pathological enlargement of superficial lymph nodes throughout the body, even if the enlargement is not pathologically confirmed as malignant lymphoma;
(2) Normal peripheral blood leukocyte count and no infantile leukocytes;
(3) No mediastinal lymph node enlargement on chest X-ray and CT examination;
(4) No lesions other than enlarged lymph nodes in the colorectal wall and tethered drainage area during surgery;
(5) Liver and spleen were not involved;
(6) Postoperative pathology confirmed malignant lymphoma.
Colorectal malignant lymphoma is very easy to be misdiagnosed in clinical work, and the reasons for misdiagnosis are analyzed as follows.
(1) The incidence of the disease is low;
②Lack of specific clinical symptoms and signs;
③Gastrointestinal tract imaging and fiberoptic endoscopy signs are similar to colorectal cancer;
④The positive rate of endoscopy and pathological biopsy is low. Lymphoma lesions are located in the submucosa and invade the mucosa at a later stage, so it is difficult to confirm the diagnosis through biopsy, and the confirmation rate cannot be compared with that of gastric cancer and colorectal cancer, and may be misdiagnosed as low differentiated adenocarcinoma; the receiving physicians do not know enough about this disease, lack meticulous analysis, and rely too much on special examination; pathologists are satisfied with the differentiation of benign and malignant lesions and lack vigilance for this disease.
In order to avoid misdiagnosis, clinicians should pay attention to the following aspects in their work.
① familiar with the clinical features, X-ray features, endoscopic features of the disease ;
②Master the correct biopsy and pathological diagnosis method, malignant lymphoma mainly depends on pathological diagnosis, sampling should be multi-directional and repeated in the same area until submucosa, usually 5-8 samples are taken at the edge of the ulcer;
③If the diagnosis is still unknown after routine examination, an autopsy should be performed as soon as possible;
④Immunohistochemistry and electron microscopy should be performed to differentiate the disease from undifferentiated carcinoma, pseudolymphoma, ulcer and inflammation if the disease is suspected but not confirmed by light microscopy. In conclusion, in order to avoid misdiagnosis, it is necessary to pay attention to the existence of this disease and be familiar with its clinical characteristics, and to improve the understanding of this disease in combination with X-ray and endoscopy.
(II) Differential diagnosis
Colorectal malignant lymphoma is a mesenchymal tissue tumor occurring in the colorectal wall, so it needs to be clinically distinguished from many mesenchymal tissue tumors that also originate from the intestinal wall and abdominal tumors that originate in the intestinal wall and/or invade the intestinal wall.
1. Colorectal cancer; can be differentiated from the following.
① Colorectal malignant lymphoma has mainly tumor components and less fibrotic components. Even if the wall of gastrointestinal tract is very thick, it still maintains a certain degree of expansion and softness. Careful observation of different simultaneous phases after scanning and enhancement can reveal certain changes in the morphology of colorectal wall, of course, barium meal examination is more intuitive and obvious;
②Lymphoma lesions with smooth and clear borders often show extensive thickening of the GI canal wall or huge GI masses, while there is no invasion in the vicinity or invasion is not obvious. The borders of colorectal cancer, on the other hand, are mostly blurred, with burrs and loss of fat layer or increased density;
Colorectal malignant lymphoma rarely causes narrowing of the lumen of the digestive tract or the degree of narrowing is less, even if the tumor is huge, it will not be completely obstructed, and sometimes the tumor destroys the nerves of the muscular layer of the canal wall but causes the expansion of the canal lumen; while left hemicolectomy and rectal cancer often cause narrowing of the canal lumen and the obstruction symptoms are often more severe;
When distant lymph node metastasis occurs in colorectal cancer, most of them already have liver metastasis, and the infiltration of lymphoma to liver is mostly manifested as diffuse enlargement with more uniform density, and rarely appears as single or multiple nodal lesions (mostly seen in primary lymphoma of liver).
2.Lymphatic tissue reactive hyperplasia Both can be seen as reactive follicles under light microscopy, but the center of lymphatic tissue reactive hyperplasia is surrounded by coat lymphocytes, with more plasma cell infiltration between follicles, diversity of proliferating cells, no heterogeneity of lymphocytes, and polyclonality of immunohistochemistry.
Small cell carcinoma of rectum; lymphoma cells are mostly distributed diffusely, and after invading smooth muscle, tumor cells grow along the smooth muscle gap to form wavy or embroidered carpet-like images, while small cell carcinoma of rectum has nesting phenomenon or organ-like structure, regional necrosis is seen in the middle of the nest, often with vascular infiltration and early local lymph node metastasis.
4.Colorectal mesenchymal tumor Both tumors are mesenchymal tumors originating from the colorectal wall, and both show similar clinical manifestations such as abdominal pain and abdominal masses. The differentiation of the two is mainly based on histological and immunohistochemical manifestations. Mesenchymal tumors have characteristic spindle-shaped and/or epithelial-like tumor cells histologically, and immunohistochemistry presents CD117 and/or CD34 positivity.
5.Appendiceal abscess; it is caused by appendiceal perforation, and the lesion is adjacent to the end of cecum and ileum, CT shows the area of lamellar or mass shadow, the edge is often blurred, gas shadow and calcification in the lesion are more characteristic, and lymph node enlargement is rare. Sometimes the cecum and the end of the ileum can be seen by the changes of the nudge.
6, Crohn’s disease Prevalent in the end of the ileum, small intestine, colon can develop at the same time. The affected intestinal wall thickening and intestinal lumen narrowing, multi-segmental, jumping distribution. Pathology is characterized by fissure-like ulceration and granulomatous inflammation of the intestinal wall.
CT shows varying degrees of intestinal wall hypertrophy in the ileocecal region and irregularity of the wall edges when the terminal ileum is involved. Lymphoma is a diffuse or limited thickening of a long segment of the intestinal canal wall and is more likely to cause intussusception.
V. Treatment
Lymphoma is a disease that can be easily spread throughout the body because of the focal distribution of lymphoma foci and the spread of lymphoma cells into the bloodstream through the thoracic duct, so most authors believe that the most reasonable treatment for colorectal malignant lymphoma should be combined with surgery. For limited lesions, radical surgery can be performed to remove the primary focus and regional lymph nodes, followed by radiation therapy.
For extensive lesions, palliative resection can be performed to remove the main tumor and prevent and relieve complications, followed by radiotherapy and/or chemotherapy. In recent years, the use of a molecularly targeted drug for CD20-positive lymphoma, melphalan, has brought the treatment of lymphoma to a new stage.
The ability to surgically remove the lesion is not only a major determinant of survival, but postoperative chemotherapy and/or radiation therapy can significantly improve the outcome of the disease.
The following treatment options are available.
①Surgery + post-operative chemotherapy and radiotherapy: suitable for stage I and II patients with small local tumors.
② Pre-operative chemotherapy + surgery + post-operative chemotherapy and radiotherapy: for patients with clinical stage III and IV or those with large local tumors and difficulties in surgical removal of tumors, as well as those whose tumors were not removed in the first surgery, 2-4 courses of chemotherapy should be administered first, and then the primary tumor should be radically removed as much as possible, followed by consolidation chemotherapy and adjuvant radiotherapy after surgery. For unresectable tumors, “load-reducing” surgery should be performed as far as possible, and silver rings should be placed at the sites with residual tumors or suspected residual tumors, followed by postoperative chemotherapy and radiotherapy.
(3) Chemotherapy alone: It is suitable for those who are advanced or cannot tolerate surgery, and can be supplemented with radiotherapy as appropriate.
(I) Surgery
Since intestinal lymphoma often infiltrates and spreads along its long axis under the mucosa, the surrounding boundary is often less obvious than that of intestinal cancer, while multicenter lesions are not uncommon, so the surgical procedure can be performed according to the requirements of colorectal cancer, and the surgical methods include local excision, radical excision and palliative surgery. Early stage lesions (stage I) do not infiltrate the whole intestinal wall and there is no regional lymph node metastasis and distant metastasis, so local excision can be cured.
Progressive lesions (stage II and III) without distant metastases require radical surgery, such as right hemicolectomy, Dixons surgery, etc. In advanced lesions (stage IV), distant metastases have already appeared and the opportunity for radical surgery is lost. For emergency surgery due to intestinal perforation or intestinal obstruction, different surgical methods should be selected depending on the patient’s general condition, abdominal cavity contamination and the degree of lesion, including radical resection with phase I anastomosis, phase II anastomosis, Hoffmans surgery, enterostomy, etc.
Intraoperatively, the intestinal cavity should be opened to check whether there are multiple lesions, pay attention to the residual tumor at the cut edge, and it is better to perform intraoperative frozen section to check the cut edge to avoid residual tumor, and pay attention to the clearance of regional lymph nodes. It should be noted that the tumor sometimes has infiltrative adhesions, and resection should try to achieve radical purpose.
(II) Radiotherapy
Radiotherapy is also one of the adjuvant treatment measures after surgery for colorectal malignant lymphoma. The main indications for radiotherapy are: after radical surgery for tumors that have invaded the plasma membrane surface or metastases in lymph nodes, radiotherapy can be supplemented; for cases with multicenter lesions or direct infiltration of surrounding organs for radical resection; after various palliative surgeries; and for postoperative local recurrence. In general, the total amount of radiotherapy is 4500cGy, if there are still residual tumor cells, additional 500-1000cGy per week; for those who have not been operated, radiotherapy for 6-8 weeks is 4500-5000cGy. However, most of the single radiotherapy will recur soon, and chemotherapy should be performed at the same time.
(C) Chemotherapy
Chemotherapy is an essential adjuvant therapy after surgery for colorectal malignant lymphoma, especially for patients with palliative surgery. Combination chemotherapy regimens including anthracyclines are very important for the treatment of intra- and extra-nodal lymphomas. There are many clinical chemotherapy regimens, and the CHOP regimen (cyclophosphamide, adriamycin, vincristine, prednisone) and the CPMP (cyclophosphamide, vincristine, methotrexate, prednisone) regimen are generally used in China, with an overall efficiency of 95.8%.
Two points should be noted in the treatment of malignant lymphoma of the colorectum.
(1) Colorectal malignant lymphoma has a tendency to be multiple primary. Therefore, preoperative colonoscopy should be comprehensive and meticulous, and intraoperative surgeons should carefully touch the whole gastrointestinal tract to avoid missing other primary lesions.
②Be alert to the complications of radiotherapy: radiotherapy can cause massive necrosis of tumor cells, leading to rapid rupture and shedding of tumor, which may cause the risk of intestinal hemorrhage and perforation. In addition, the rapid destruction of tumor cells can cause hyperuricemia and uremia. Therefore, when chemotherapy is administered to the primary tumor, appropriate chemotherapy regimen and drug dose should be selected, and urine should be alkalized and urine volume should be closely observed to prevent uremia caused by hyperuricemia.
Radiotherapy for primary tumor should be cautious, and radiotherapy is generally used as adjuvant irradiation for those with poor chemotherapy efficacy, and attention should be paid to low residue or residue-free diet during radiotherapy, and to keep bowel fluent to prevent intestinal bleeding and perforation.
(iv) Treatment of melphalan
Meroval is a human-mouse chimeric anti-CD20 monoclonal antibody developed by genetic engineering. The variable region is of mouse origin and specifically binds B-cell CD20. the constant region is the human k and human IgG1Fc segment, which is synergistic with human active cells and may be associated with rare host resistance reactions. The mechanism of B-lymphocyte clearance by melphalan is multifaceted and can mobilize host immunoreactive cells via the Fc segment.
The specific mechanisms are.
① Binding CD20: CD20 is expressed in normal, neoplastic pre-B cells, mature B cells, but not in hematopoietic stem cells, plasma cells and other hematopoietic cells, and is expressed in more than 90% of B-cell lymphomas. because it is not masked or modified, it is suitable for targeted therapy. Monoclonal chimeras have a more potent host effector mediating function and lower immunogenicity than murine antibodies.
(ii) Induction of antibody-mediated cytotoxic effects and complement-mediated cytotoxic effects: Complement-mediated cell death induced by melphalan was found to occur in vitro via caspase-independent mechanisms, including reactive oxygen species cluster (ROS) reproduction.
(iii) Induction of apoptosis (programmed death): anti-CD20 monoclonal antibody directly induces apoptosis and modulates the mechanism of chemotherapy-induced apoptosis. In addition, its activity is cell cycle independent and resensitizes chemotherapy-resistant lymphocytes.
Meroval was first approved in 1997 for the treatment of low-grade malignant or follicular, relapsed or recalcitrant CD20-positive B-cell NHL in the U.S. It was approved in 1998 in all European countries for the treatment of stage III/IV, follicular, chemoresistant or relapsed (greater than or equal to 2 relapses) NHL. The dose was 375 mg/m2 once a week for 4 weeks, with repeat dosing at 6 months for up to 4 courses in patients with stable disease.
The efficacy rate was 65%, with 27% in complete remission. Combination therapy with interleukin-12 (IL-12), granulocyte colony-stimulating factor (G-CSF), alpha-2a interferon, CHOP, and radiotherapy/radioimmunotherapy is expected to improve the efficacy.
The side effects caused by melphalan are mostly injection-related symptoms. Mild-moderate are mostly seen with the first injection and are mostly infusion reactions caused by the injected drug. The reactions occur 30 minutes to 2 hours after the first infusion and decrease with multiple infusions. More serious side effects include allergic reactions in some cases, such as hypotension, bronchospasm and angioedema; arrhythmias and angina pectoris in patients with a history of heart disease. Studies have shown that the mechanism of the main side effects of melphalan may be related to rapid activation of complement, lymphocytolysis and release of TNF-α.
The prognosis of colorectal malignant lymphoma is related to the tumor classification, the extent of infiltration, the presence of metastasis, whether it can be resected, and whether radiotherapy or chemotherapy is given after surgery. The prognosis of colorectal malignant lymphoma is poor if the tumor invades extensively, both mesenteric lymph nodes and supra-diaphragmatic lymphoma are invaded, radical resection is not possible and postoperative comprehensive treatment is not adopted. In general, the 5-year survival rate of colorectal malignant lymphoma is about 39%, and the 5-year and 10-year survival rates of those with surgical resection followed by chemotherapy and/or radiotherapy are 67% and 61%, respectively.