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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 95-100

Analysis of clinical features and prognostic factors of AIDS-related lymphoma


1 Department of Obstetrics and Gynecology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
2 Department of Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning; Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
3 Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
4 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
5 Department of Infectious Diseases, Hubei AIDS Clinical Training Central, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

Date of Submission25-Jun-2021
Date of Acceptance11-Sep-2021
Date of Web Publication5-Apr-2022

Correspondence Address:
Prof. Hengning Ke
Hubei AIDS Clinical Training Central, Zhongnan Hospital of Wuhan University, Wuhan, Hubei
China
Dr. ZhiYan Lu
Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/RID.RID_5_22

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  Abstract 


OBJECTIVE: To analyze the clinical characteristics, pathological characteristics, and prognostic factors of AIDS-related lymphoma (ARL).
MATERIALS AND METHODS: This was a retrospective study of the clinical characteristics, diagnosis and treatment process, and survival status of 32 patients with ARL. The patients were divided into a survival group and nonsurvival group according to their prognosis, and the factors affecting survival were analyzed. The patients' clinical characteristics were analyzed according to symptoms, sex, age, and laboratory indicators such as the lactate dehydrogenase (LDH) concentration, number of CD4+ T cells, Ann Arbor stage, pathological typing, and international prognostic index (IPI) score. A univariate regression analysis was performed to compare the clinical characteristics of the treatment group and nontreatment group. The impact of chemotherapy and combined antiviral therapy on survival time was assessed.
RESULTS: Thirty-two patients were included in the study; 31 were male and 23 were aged >40 years. The average LDH concentration was 639.8 U/L, and the average CD4+ lymphocyte count was 167 cells/μL. Diffuse large B-cell lymphoma was present in 40.6% (13/32) of the patients; a B-lymphocyte source accounted for 90.6% (29/32) of cases, and a T-lymphocyte source accounted for 9.4% (3/32). The proportion of patients who received anti-lymphoma treatment was 84.4% (27/32). Twenty-three patients died during follow-up and nine survived. Univariate analysis showed that the prognostic factors were age, the CD4+ T-lymphocyte count, and the IPI score. The average progression-free survival (PFS) time in the highly active antiretroviral therapy (HAART) group before chemotherapy was 4.81 months, while the average PFS time without antiviral therapy before chemotherapy was about 1.91 months. This difference was statistically significant. The median 2-year survival time in patients who received antiviral therapy before chemotherapy was 33.3 months, while that in patients who did not receive antiviral therapy was 27.3 months. Early HAART therapy combined with standardized chemotherapy was shown to improve the patients' prognosis. It also improved the overall survival (OS) rate and PFS time. However, there was no significant difference in the OS rates between 1 and 2 years.
CONCLUSION: The CD4+ T-cell count and IPI score were key factors affecting the prognosis of patients with ARL. An increased LDH concentration was also a prognostic factor. A certain correlation between the disease severity and prognosis was found. The use of standard anti-lymphoma treatment can effectively improve the survival rate of patients.

Keywords: AIDS, anti-lymphoma treatment, clinical features, lymphoma, prognosis


How to cite this article:
Gong Y, Gong X, Zhang K, Song L, Li Y, Ke H, Lu Z. Analysis of clinical features and prognostic factors of AIDS-related lymphoma. Radiol Infect Dis 2021;8:95-100

How to cite this URL:
Gong Y, Gong X, Zhang K, Song L, Li Y, Ke H, Lu Z. Analysis of clinical features and prognostic factors of AIDS-related lymphoma. Radiol Infect Dis [serial online] 2021 [cited 2022 Aug 9];8:95-100. Available from: http://www.ridiseases.org/text.asp?2021/8/3/95/342622




  Introduction Top


Human immunodeficiency virus (HIV) infection causes deficiencies in the human immune system. Tumors are more likely to develop in HIV-infected patients than in healthy persons.[1] Although the use of high-efficiency antiretroviral therapy (ART) can significantly reduce the mortality of HIV-infected patients, these patients are still at high risk for tumors, especially AIDS-related lymphoma (ARL).[2] ARL, particularly non-Hodgkin's lymphoma (NHL), is the most common malignant tumor associated with HIV infection. Its incidence is 34.5 times higher than lymphoma in the general population.[3] The population of patients with ARL has rapidly grown in recent years, and such patients exhibit a variety of clinical manifestations. Furthermore, ARL can be easily misdiagnosed, leading to a poor prognosis. In this study, the clinical data of 32 patients with ARL in Zhongnan Hospital of Wuhan University were retrospectively analyzed. The clinical characteristics, survival status, and related prognostic factors of these patients were analyzed.


  Materials and Methods Top


Study design and patients

Patients with ARL who were admitted to the Zhongnan Hospital of Wuhan University from January 2016 to December 2020 and met the inclusion criteria were selected for enrollment. The two inclusion criteria were hospitalization in our hospital before the follow-up deadline (December 31, 2020) for the diagnosis of ARL or receipt of treatment and a complete treatment history available from the medical record. The collected clinical data of patients with ARL included age, sex, time of HIV diagnosis, time of the first admission to the hospital, lactate dehydrogenase (LDH) concentration, erythrocyte sedimentation rate, CD4+ T-lymphocyte count at the time of lymphoma diagnosis, ART status, international prognostic index (IPI) score, Ann Arbor stage, pathological classification, and chemotherapy status. The CHOP regimen (cyclophosphamide, doxorubicin, and vincristine) and prednisone were used together. The flow chart of the experimental design is shown in [Figure 1].
Figure 1: The flow chart of our research

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Diagnostic criteria

The diagnosis of AIDS conformed to the standards in the “Guidelines for the Diagnosis and Treatment of AIDS” issued by the Chinese Medical Association in 2015.[4] Lymphoma was classified according to the 2008 World Health Organization classification of the lymphoid hematopoietic system, and all patients' diagnoses were confirmed by histopathology and immunohistology.

Follow-up

The survival period of all patients was calculated from the date of ARL diagnosis, and the survival prognosis was evaluated based on the survival period. The survival period was defined as the time interval from the diagnosis of ARL to death or the last follow-up. Overall survival (OS) was defined as the time period from a clear diagnosis to death or the end of follow-up or, for patients who were lost to follow-up, to the last known date on which they were alive. The follow-up deadline was December 31, 2020.

CD4+ T-lymphocyte count

All samples were tested at the laboratory of the AIDS Training Center of Zhongnan Hospital of Wuhan University. The fluorescent-labeled antibody, tester, and flow cytometer used in this study were obtained from Beckman Coulter (Brea, CA, USA).

Statistical analysis

SPSS 23.0 statistical software (IBM Corp, Armonk, NY, USA) and GraphPad Prism 8.0.1 graphics software (GraphPad Software, San Diego, CA, USA) were used for statistical processing. Normally distributed measurement data are presented as mean ± standard deviation, and nonnormally distributed data are presented as median (interquartile range). The measurement data were analyzed using the Chi-square test. Fisher's probability method was used for data that did not meet the Chi-square test, and the Kaplan–Meier method and log-rank test were used for survival analysis. P < 0.05 was considered statistically significant.


  Results Top


Clinical characteristics

Most patients with ARL were male, accounting for 96.9% (31/32), and >40 years of age, accounting for 71.9% (23/32). The most common lesion site was the lymph nodes, accounting for 65.6% (21/32) of cases. Clinical symptoms included masses (14/32), abdominal pain (8/32), and scrotal swelling (3/32). At admission, 23 patients had an increased LDH concentration and 17 patients had an increased erythrocyte sedimentation rate. When the disease was diagnosed, the average CD4+ T-lymphocyte count was 167 cells/μl, and 21 patients had a count of <200 cells/μl. Most tumors originated from B-lymphocytes, accounting for 90.6% (29/32) of cases. Among them, diffuse large B-cell lymphoma (DLBCL) accounted for 40.6% (13/29) of cases. A total of 71.9% (23/32) of patients had Ann Arbor stage III to IV disease. The high-risk group (IPI score of 3–5) accounted for 59.4% (19/32) of patients [Table 1]. Eleven patients discontinued treatment and then died. During follow-up, 12 patients died, 4 were completely cured, and 9 survived.
Table 1: Comparison of clinical characteristics of 32 patients with AIDS-related lymphoma in the treatment and nontreatment groups

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Pathological features

Three cases of ARL were confirmed by examination of surgically resected specimens, 29 cases by biopsy, and 3 cases by bone marrow examination. Eighteen cases occurred only in the lymph nodes, two in the liver, three in the testis, three in the small intestine, two in the stomach, two in the brain tissue and lymph nodes, one in the nasal cavity and lymph nodes, and one in the anus. With respect to the pathological type, 29 cases of ARL originated from B lymphocytes. Thirteen cases originated from DLBCL, accounting for 40.6% (13/32); 5 cases originated from Burkitt's lymphoma, accounting for 15.6% (5/32); 5 cases originated from mucosa-associated lymphoid tissue lymphoma (5/32); 1 case originated from follicular lymphoma (1/32); and 5 cases could not be further classified (5/32). Three cases originated from T-lymphocytes: Two from peripheral T-cells and one from extramural NK/T cells.

Survival analysis of patients with AIDS-related lymphoma

Twenty-three patients died, 11 developed rapid progression, 20 underwent combined ART, and 27 were cured by chemotherapy. Univariate analysis showed that the LDH concentration, IPI score, and Ann Arbor stage were significantly different between the treatment group and nontreatment group (P < 0.05); however, there was no significant difference in the erythrocyte sedimentation rate, CD4+ T-cell count, or administration of highly active ART (HAART) between the two groups [Table 2]. progression-free survival (PFS) was significantly increased in the chemotherapy + HAART group compared to the nontreatment group [Figure 2]a. ART before chemotherapy was shown to increase the PFS time. Patients who received HAART before chemotherapy had an average PFS time of 4.81 months, whereas those who received only ART before chemotherapy had an average PFS time of only 1.91 months. There was a significant difference between the use and nonuse of HAART before chemotherapy [Table 3] and [Figure 2]b. The median survival time of patients with ARL who received ART before chemotherapy was 33.3 months, whereas that in patients who did not receive ART was 27.3 months [Table 3]. The patients were divided into four groups according to whether they were treated with ART and whether their treatment was combined with ART before chemotherapy. The OS rate was highest in the chemotherapy combined with ART group, followed in descending order by the chemotherapy only group, ART only group, and untreated group [Figure 2]a. However, the 1-year and 2-year survival rates were not significantly different among these groups [Figure 2]b.
Figure 2: Kaplan–Meier plot comparing overall survival and progression-free survival (PFS) for patients receiving different treatment regimens (a) PFS was significantly different between the chemotherapy + highly active antiretroviral therapy (HAART) group and the nontreatment group (P = 0.04). (b) PFS was significantly different between the HAART before chemotherapy group and the non-treatment group (P = 0.016)

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Table 2: Clinical characteristics and prognosis of 32 patients with AIDS-related lymphoma

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Table 3: Comparison of progression-free survival and 2-years overall survival in highly active antiretroviral therapy and nonhighly active antiretroviral therapy groups

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  Discussion Top


Patients with AIDS have an increased risk of developing malignant tumors. More than 28% of patients with AIDS die of malignancy, and more than 40% of the malignancies are ARLs. ARL is an aggressive, rapidly growing malignant tumor. Without timely administration of standardized treatment at the time of diagnosis, such patients may die within a few weeks or months. The introduction of HAART and the resultant sustained control of HIV replication and consequent immune reconstitution have dramatically decreased HIV-associated morbidity and mortality. At the time of this writing, there were more than 35 million HIV-infected people worldwide.

Most of the patients with ARL in this study were male, accounting for 96.9% (31/32) of all patients; this may be related to the higher HIV infection rate in men than in women. This finding is consistent with previous studies.[5],[6] Gopal, et al[5] found that the age of patients who received combination ART and were then diagnosed with ARL was increased by 5 years than not, with the widespread use of ART. In another study, the average age of patients with ARL from 2004 to 2008 was 39 years,[7] whereas the average age of patients with ARL in the present study was 46 years. Twenty patients in this study were treated by ART, and there was no difference in the 1-, 2-, and 3-year survival rates according to whether the patients received HAART before chemotherapy. In addition, some patients or their families who refused treatment might have also affected the OS rates. With the use of HAART before chemotherapy, the median PFS time was approximately 4.81 months, whereas that without HAART was only 1.91 months. This shows that the use of HAART before chemotherapy can significantly improve the PFS time. Therefore, combination ART should be the first choice for patients with ARL who cannot receive chemotherapy.

The pathological manifestations of ARL are heterogeneous. The most common type is NHL, among which Burkitt's lymphoma and DLBLC are the most common. The second most common type is HIV-related idiopathic lymphoma, including primary exudation lymphoma and oral plasmablastic lymphoma, among which T-cell lymphoma is rare.[8] The main pathological type of ARL in our study was B-cell-derived lymphoma, accounting for 90.6% (29/32) of cases, among which 40.6% (13/29) were DLBCL. Furthermore, 43.8% (14/32) of patients with ARL were found to be infected with HIV after they had been diagnosed with lymphoma. Lymphoma may be the first symptom of AIDS. Therefore, patients with lymphoma should be routinely screened for HIV. Patients with clinical manifestations such as fever, swollen lymph nodes, and abdominal pain that cannot be explained by common opportunistic infections should undergo a lymph node puncture, gastroscopy, colonoscopy, or biopsy. These procedures will help to diagnose HIV infection in a timely manner and facilitating smooth administration of anti-viral and anti-lymphoma treatment.

Our study suggests that a low CD4+ T-lymphocyte count is an independent risk factor for ARL; it is also an important factor affecting the prognosis.[9] The average number of CD4+ T-lymphocytes in the patients with ARL in this study was 167 cells/μL. We found that patients with ARL who had a CD4+ T-lymphocyte count of >200 cells/μL had a higher proportion of anti-NHL treatment in this study. We speculated that patients with ARL have a lower CD4+ T-cell count and cannot tolerate chemotherapy. During the anti-NHL treatment, patients were susceptible to infection and bone marrow suppression; therefore, the anti-lymphoma treatment was discontinued. An increased CD4+ T-lymphocyte count reduces the impact of AIDS-related opportunistic infections on the prognosis, enabling most patients with NHL to undergo standardized chemotherapy. Many studies have shown that starting HAART as early as possible can reduce the cancer risk by 64%. HAART can not only inhibit HIV but also inhibit cancer virus infection and reduce inflammation through other mechanisms.[10],[11]

Our study also suggests that chemotherapy combined with ART can effectively improve the OS rate and PFS time of patients with ARL. A meta-analysis by the British HIV Association[12] also showed that combination ART can significantly reduce AIDS-related DLBCL patients and improve the prognosis. However, there were no significant differences in the 2-year OS rate or PFS depending on whether ART was administered. Another retrospective study also obtained similar results.[13] The reason for this finding might be that patients who did not receive intensive chemotherapy had lower CD4+ T-cell counts, making the patients more susceptible to opportunistic infections. Although we did not dynamically detect the patients' CD4+ T-cell counts, no serious opportunistic infections were observed after chemotherapy. Recent studies have also shown that after the combined application of HAART and standardized chemotherapy in patients with ARL, the survival period was similar to that of HIV-negative patients with lymphoma.

In our study, the LDH concentration was an independent risk factor that affected the prognosis in patients with ARL. A certain correlation was found between the serum LDH concentration and AIDS-related DLBCL patients' survival, which is basically consistent with the results of other studies. The LDH concentration is among the five indicators that comprise the IPI score. LDH is considered one of the most independent and important prognostic factors. Studies have also supported the important role of LDH in lymphoma detection. A higher LDH concentration is associated with a greater tumor burden in patients with lymphoma, a higher degree of malignancy, and a worse prognosis.[14] This might be explained by the fact that patients with AIDS-related complications (e.g., tuberculosis, lymphoma) have suppressed immune function and might have multiple simultaneous infections, resulting in poor physical function.

This study had two main limitations. First, the sample size was small, and the calculation of the survival rate may not have been accurate enough. Second, most patients had advanced-stage ARL, and the mortality rate was high. In the future, the research scope will be expanded to include multiple institutions and patients with all stages of disease.


  Conclusion Top


ARL was mainly derived from B-lymphocytes in this study, and DLBCL was the most common type. The clinical symptoms were diverse and the mortality rate was higher than that of other types. The main indicators of a poor prognosis were a high LDH concentration, a high IPI score, and the pathological subtype. Early HAART combined with standardized chemotherapy could be useful for improving patients' prognosis and increasing the OS rate and PFS time.

Acknowledgment

We thank Angela Morben, DVM, ELS, from Liwen Bianji (Edanz) (www.liwenbianji.cn/) for editing the English text of a draft of this manuscript.

Ethic statement

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University. Signed informed consent was obtained from all patients before any study-specific procedure was performed.

Financial support and sponsorship

National Nature Project (31760263), Chinese Center for Disease Control and Disinfection Special Fund (201865); Science and Technology Innovation Cultivation Fund of Zhongnan Hospital of Wuhan University (znpy2018033); Key Project of Xianning Central Hospital (2020XYA002).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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