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Primary gastrointestinal lymphoma (PGIL) accounts for 30% to 40% of extranodal lymphomas, with the most common tissue subtype being diffuse large B-cell lymphoma (DLBCL).
Due to the relative rarity of PGIL, the current data guiding treatment are limited, which treatment strategy to adopt is controversial, how to determine the influencing factors of PGIL prognosis, and further optimize the existing treatment strategy remains to be explored
.
Yimaitong sincerely invited Professor Ou Jinping of Peking University First Hospital to be interviewed to share the progress of PGIL diagnosis and treatment and related research
.
Medical Pulse: PGIL is the most common type of extranodal lymphoma, mainly involving the stomach, followed by the small intestine and ileocecal part, without liver, spleen and other lymphoid tissues and lymph node involvement
.
Could you please talk about the difficulties in the diagnosis of PGIL based on your clinical experience?
Professor Ou Jinping
Because PGIL primarily affects the gastrointestinal tract, its symptoms can be easily confused with other gastrointestinal disorders, delaying diagnosis
.
The difficulties of its diagnosis are: (1) the number of outpatients in the Department of Gastroenterology is large, and there are many common types of diseases, including peptic ulcer, chronic gastritis, chronic enteritis and digestive tract tumors, etc.
, compared with the low incidence of PGIL, which means that PGIL needs to be distinguished from many more common digestive tract diseases (such as gastric cancer, bowel cancer); (2) The typical B symptoms of lymphoma, that is, fever, night sweats, and weight loss, can appear in advanced PGIL but the incidence is not high, so the diagnosis based on clinical symptoms is more difficult; (3) Some patients need to undergo pathological examination after surgery to determine the type of disease, and some patients have difficult conditions such as perforation, bleeding or intestinal obstruction before diagnosis, which affects their survival and prognosis
.
Yimaitong: It is understood that your center has conducted a number of retrospective studies to explore the factors affecting the survival of patients with PGIL and the differences
in prognosis of patients under different treatment modes.
Based on the results of the study, how do you choose treatment for PGIL patients? What do you think of the place of rituximab-containing immunochemotherapy in the treatment of PGIL?
Professor Ou Jinping
Our center has cooperated with a number of well-known domestic lymphoma diagnosis and treatment centers to carry out PGIL-related research, among which, the retrospective study for PGIL patients not only discusses the factors affecting the survival of patients and the optimization of treatment plans, but also discusses the relationship between complications such as gastrointestinal obstruction, bleeding, and perforation and the prognosis of patients [1-2].
。 Univariate analysis showed that age, group B symptoms, large masses, PGIL Lugano stage, IPI score, pathological cell type, pathological type, lesion location, and severe gastrointestinal complications could affect overall survival (OS, P value < 0.
05), and multivariate analysis showed that IPI score (relative risk [RR] 3.
848, 95% CI 2.
284-6.
482, P<0.
001), pathological cell type (RR 2.
394, 95% CI 1.
296-4.
421, P=0.
005) and lesion site (RR 1.
971, 95% CI 1.
261-3.
081, P=0.
003) were independent risk factors
for OS in patients with PGIL 。 Compared with uncomplicated patients (5-year OS rate was 72.
5%), the 5-year OS rate of patients with gastrointestinal bleeding, intestinal obstruction and organ perforation was significantly reduced (60.
1%, 56.
8%, 30.
0%, respectively), and the survival of patients with ≥ two complications was worse, with a 5-year OS rate of only 26.
1%.
For the choice of PGIL treatment regimen, the clinical more commonly used is rituximab combined with chemotherapy immunochemotherapy regimen, our center has previously carried out retrospective studies and many large centers at home and abroad have shown that the addition of anti-CD20 monoclonal antibody on the basis of chemotherapy alone significantly improves the efficacy of patients, by improving the remission rate of patients, thereby improving the survival and long-term quality of life of
patients.
Chemotherapy-related gastrointestinal complications can affect the effectiveness of treatment, and severe can affect the survival of
patients with PGIL.
Could you please talk about what preventive and therapeutic measures can be taken to intervene?
Professor Ou Jinping
Chemotherapy-related gastrointestinal complications include bleeding, perforation, intestinal obstruction and several complications combined, the more complications that occur, the worse the prognosis of patients, and the mortality rate of patients during induction chemotherapy is also increased, so how to reduce chemotherapy-related gastrointestinal complications is one of the
research hotspots in recent years.
Based on relevant literature at home and abroad and the experience of large centers, immunochemotherapy combined with surgical intervention has certain significance
in improving the prognosis of patients.
Surgery is generally not recommended before chemotherapy in patients with gastric lymphoma, but surgical intervention
is indicated if the patient develops serious complications (such as bleeding or perforation) after chemotherapy.
For intestinal lymphoma, regardless of the pathological type, it is recommended that patients undergo chemotherapy after surgical resection, or chemotherapy combined with surgery followed by chemotherapy to maintain the treatment mode, which can help patients safely pass the induction chemotherapy period, improve their tolerability and disease remission rate, and thus improve the long-term survival of patients [3].
Pharma: Your team recently published an article in the journal Clinical Epigenetics entitled "5-Hydroxymethylation alterations in cell-free DNA reflect molecular distinctions of diffuse large B cell lymphoma at different primary sites.
" [4], the differences in prognosis of DLBCL at different primary sites and the guiding significance
of 5-hydroxymethylation changes (5hmC) in this context were discussed.
Could you please explain the results of this study and its implications for clinical treatment?
Professor Ou Jinping
Although there have been more and more explorations and studies on serum cell-free DNA in tumors in recent years, there is still a certain distance
from its real application in clinical practice.
Our center analyzes the specific types of primary extranodal lymphoma, and uses 5hmC to reflect the changes of serum free DNA, which is more convenient and time-saving than the commonly used methods
.
Studies have found that the primary site is related to clinical features and is a key factor
affecting the prognosis of patients with DLBCL.
Patients with primary gastric DLBCL and lymph node involvement have a good prognosis, while patients with primary central nervous system DLBCL have the worst prognosis, followed by primary testicular DLBCL and primary intestinal DLBCL
。 In addition, 5hmC can not only reflect the different clinical characteristics of DLBCL, but also have significant molecular differences in DLBCL patients at different primary sites, so it can be used as an effective epigenetic biological marker, which may help to develop effective methods to determine the primary site of DLBCL, assist in the diagnosis of lymphoma, and judge the efficacy and prognosis of existing treatment options, including remission rate and long-term survival of patients
.
At the same time, with the in-depth study of tumor signaling pathways, we may find effective therapeutic targets or better treatment options for a certain tumor to further improve the efficacy
.
As you said, rituximab-containing immunochemotherapy regimens are an important treatment option
for patients with PGIL.
As a new anti-CD20 monoclonal antibody, have you carried out PGIL-related explorations? Please look forward
to the use of obinutarzumab in PGIL.
Professor Ou Jinping
Anti-CD20 monoclonal antibody-based immunochemotherapy regimens have become an important treatment option for patients with PGIL, and in order to further optimize this regimen, our center has organized and participated in several clinical trials
.
As the world's first individualized and glycosylated type II anti-CD20 monoclonal antibody, obinutuzumab not only reduces immunogenicity and has more stable efficacy compared to rituximab, but also enhances the killing effect of cytotoxicity, enhances antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) and induces direct cell death, which can further improve the tumor killing effect and is expected to become an important pillar of immunochemotherapy in the field of lymphoma
。
Based on its innovative mechanism of action, we have observed further efficacy
improvements in replacing rituximab with obinutarzumab in some patients with relapsed and refractory PGIL.
One of the patients with follicular lymphoma converted to DLBCL had been given rituximab multiple times in the past, and after treatment with obinutuzumab combined with gemcitabine, cisplatin, and dexamethasone (GDP) when it progressed again, the patient achieved significant remission, and after four courses of PET/CT evaluation of complete molecular response (CMR), indicating that the new anti-CD20 monoclonal antibody obinutuzumab still has a good efficacy in refractory cases of rituximab
。 At the same time, our center is conducting relevant long-term research and looks forward to the publication of relevant research results
in the future.
brief summary
Since PGIL mainly affects the gastrointestinal tract, its symptoms are easily confused with other digestive tract diseases, and there are many difficulties in diagnosis
.
In the treatment of PGIL, the significance of surgery should be emphasized, surgery combined with immunochemotherapy is the preferred regimen for intestinal lymphoma, and comprehensive management of complications is an important way to improve the remission rate and survival rate
.
Anti-CD20 monoclonal antibody-based immunochemotherapy is a common treatment option for PGIL, and how to reduce chemotherapy-related complications remains to be further explored
.
As a new anti-CD20 monoclonal antibody, obinutuzumab has certain application prospects in PGIL patients, and it is expected that more research results will be published in the future to prove its benefit
.
Professor Ou Jinping
Doctor of Medicine, Deputy Chief Physician, Graduate Supervisor, Deputy Director of Department of Hematology, Peking University First Hospital
He used to be a youth committee member of the Beijing Hematology Branch of the Chinese Medical Association
Member of Beijing Hematology Branch of Chinese Medical Doctor Association
Member of the Expert Committee of the Hematological Oncology Professional Committee of the Chinese Anti-Cancer Association, and the Chinese Working Group on Myelodysplastic Syndrome and Myeloproliferative Tumors
Member of Lymphoma Branch of Chinese Medical Education Association
Member of the lymphoid hematology group of the Early Cancer Screening Committee of the Beijing Anti-Cancer Association
Medical expert of Beijing Medical Association
Reviewer of several Chinese Medical Association journals
References
1.
Haiyan Yang, Meng Wu, Ye Shen, et al.
Treatment Strategies and Prognostic Factors of Primary Gastric Diffuse Large B Cell Lymphoma: A Retrospective Multicenter Study of 272 Cases from the China Lymphoma Patient Registry.
Int.
J.
Med.
Sci.
2019, Vol.
16:1023-31.
2.
Shen Y, Ou J, et al.
Influence of Severe Gastrointestinal Complications in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.
Cancer Manag Res.
2021 Feb 4; 13:1041-1052.
3.
Moran Wang, Shengling Ma.
et al.
Surgery shows survival benefit in patients with primary intestinal diffuse large B-cell lymphoma: A population-based study.
Cancer Medicine.
2021; 10: 3474–3485.
4.
Shen Y, Ou J, et al.
5‑Hydroxymethylation alterations in cell‑free DNA refect molecular distinctions of diffuse large B cell lymphoma at different primary sites.
Clin Epigenet 14, 126 (2022).
Edited by Chole: Reviewed by Evelyn: Crafted by Moly: Cherry
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