Abstract
Kaposi sarcoma (KS) is the most common cancer in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS). In 1994, Chang and Moore discovered Kaposi sarcoma associated herpesvirus for the first time in KS lesions in AIDS patients. KS is a low-grade mesenchymal neoplasm of blood and lymphatic vessels that primarily affects the skin, although the disease may become disseminated to the lymphatic system, lungs, airways, or abdominal viscera. In this research, clinical characteristics and treatment of patients of Kaposi sarcoma were retrospectively analyzed in Hotan District, Xinjiang China. We look into the clinical traits, prognosis, and therapy of Kaposi sarcoma. From May 2017 to August 2022, 32 patients were treated in the People’s Hospital of Hotan District, Xinjiang Uygur Autonomous Region, China. Twenty-two of these were classic Kaposi sarcomas (cKS), and 10 of these were Kaposi sarcomas linked to AIDS (AIDS-KS). The majority of KS patients were Uyghur. In terms of age at onset, AIDS-KS patients were younger than cKS patients. cKS and AIDS-KS are most frequently manifested in the feet and lower limbs. Ten patients with AIDS-KS have treated with combination antiretroviral therapy (combination antiretroviral therapy) combination chemotherapy, 5 of 10 patients had a complete response, 2 patients achieved partial response, the overall effective rate was 70%, and CD4 + T cells were greater than before. For cKS and AIDS-KS, the median overall survival was 56 and 50.8 months, respectively (P > .05). As a result, antiviral combination chemotherapy can also improve the prognosis of AIDS-KS patients.
Keywords: chemotherapy, clinical features, combination antiretroviral therapy, Kaposi sarcoma, prognosis
1. Introduction
Kaposi sarcoma (KS) is the most common cancer in individuals living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) today.[1] In Africa, where Kaposi sarcoma associated herpesvirus (KSHV) and HIV infections are highly prevalent, KS is among the most common cancer type in men overall.[2] KSHV was first isolated from KS lesions in patients with AIDS by Chang and Moore in 1994[3] and was later established to be the etiologic agent for KS in several epidemiologically distinct populations.[4] Subsequent studies showed primary effusion lymphoma, an unusual lymphoma associated with AIDS, and KSHV- multicentric Castleman disease were also associated with and caused by KSHV.[5,6] Here we report and summarize the clinical features of 32 cases of Kaposi sarcoma in Hotan district of Xinjiang Uygur Autonomous of China. The primary endpoint of this study was overall survival (OS), and secondary endpoints included overall efficacy and toxicity.
2. Material and methods
Patients selection Patients data in the People’s Hospital of Hotan District, Xinjiang Uygur Autonomous Region of China were retrospectively reviewed. We enrolled 22 cases of classic Kaposi sarcoma (cKS) patients and 10 cases AIDS-related Kaposi sarcoma (AIDS-KS) with complete follow-up from May 2017 to August 2022. Most cases, human herpesvirus type 8 (HHV-8) detection was completed by PCR with ORF-K1, ORF26. All patients were diagnosed based on pathological examination.
2.1. Data collection
Patient baseline and clinical data, including age, sex, laboratory tests (blood routine; blood metabolic panel: liver and kidney function) and imaging examination [ultrasound (Philips EPIQ Elite; Philips Medical Systems B.V.) for superficial lymph nodes, computerized tomography (CT; Siemens 08098027; Siemens AG) for chest, abdomen, and pelvic]. Changes in the number of CD4 + T lymphocytes in patients with AIDS-KS including before and after treatment. The Brambilla staging system divides KS into 4 stages; Patchy nodular stage; Infiltrative phase; Florid stage for exuberant; Disseminated stage. All patients gave written informed consent, and approval for the study was obtained from the Institutional Review Board, which conformed to the standards of the Declaration of Helsinki.
2.2. Treatment of classic Kaposi sarcoma
Twenty-two cKS patients underwent the following treatment; Chemotherapy: Chemotherapy cycles was 4 to 6 (Ifosfamide 2g/m2 d1–3 combined with liposomal doxorubicin 20 mg/m2 d1, 28 days a cycle); Radiotherapy: low-dose radiotherapy, with a total amount of 30 Gy; Immunotherapy: Interferon-alpha 600 IU intramuscularly every other day, prednisone 10 to 15 mg/day, thalidomide 50 mg twice/day for at least 3 to 6 months; Support for symptomatic treatment: Red cell suspensions are transfused in patients with anemia.
2.3. Treatment of AIDS-related Kaposi sarcoma
Ten of AIDS-KS patients were treated with chemotherapy for 4 to 6 cycles (Ifosfamide 2g/m2 d1–3 combined with liposomal doxorubicin20mg/m2 d1, 28 days a cycle) combination antiretroviral therapy (Zidovudine/Tenofovir + Lamivudine + Efavirenz/Kaletra).
2.4. Efficacy and adverse effects
Thirty days after all treatment, the PET-CT was utilized to evaluate the treatment efficacy. Based on the NCCN 2021 guideline, the treatment response of KS is divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive diseases (PD). According to the WHO standard, the acute and subacute adverse cancer drug reactions were also applied to evaluate the adverse effects.
2.5. Statistical analysis
All data were analyzed by the SPSS version 18.0 software (SPSS, Chicago, IL). The survival curves were constructed by the Kaplan–Meier method. OS was defined as the interval from the diagnosis of KS to death or the end of follow-up.
3. Results
3.1. Baseline characteristics
The histopathological diagnoses of all KS cases were confirmed through the examination of archived hematoxylin and eosin slices (Fig. 1). Of the 22 patients with cKS, 16 were Uyghurs and 6 were Han patients, of whom 18 were males and 4 were females. The age ranged from 33 to 81 with the median of 60 years old. Among the 10 AIDS-KS patients, there were 9 Uyghurs and 1 Han patients, including 9, 9 males, and 1 female, the age ranged from 25 to 75 with the median of 50 years old (Table 1). Both types of KS Patients were more likely to be male than female. HIV transmission is mainly through homosexual (8 cases) and heterosexual (2 cases).
Figure 1.
Histopathology of KS lesions (H&E staining at (A) x100 and (B) x200 magnification). KS = Kaposi sarcoma.
Table 1.
Distribution of skin lesions and age.
| Group | Foot (%) | lower limbs(%) | Hands (%) | Upper limbs (%) | Trunk (%) | Face and neck (%) | Mouth (%) | Organ (%) | Age | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 21–30 (%) | 31–40 (%) | 41–50 (%) | 51–60 (%) | 61–70 (%) | 71–80 (%) | 81–90 (%) | |||||||||
| cKS | 13 (40) | 6 (19) | 5 (16) | 4 (13) | 2 (6) | 1 (3) | 0 (0) | 4 (13) | 0 (0) | 2 (6) | 4 (13) | 4 (13) | 8 (25) | 3 (9) | 1 (3) |
| AIDS-KS | 6 (19) | 4 (12) | 3 (9) | 2 (6) | 5 (16) | 3 (9) | 2 (6) | 3 (9) | 1 (3) | 2 (6) | 2 (6) | 4 (13) | 0 (0) | 1 (3) | 0 (0) |
| Total | 19 (59) | 10 (31) | 8 (25) | 6 (19) | 7 (22) | 4 (13) | 2 (6) | 7 (3) | 1 (13) | 4 (19) | 6 (22) | 8 (25) | 8 (25) | 4 (13) | 1 (3) |
AIDS = acquired immunodeficiency syndrome, AIDS-KS = Kaposi sarcomas linked to AIDS, cKS = classic Kaposi sarcomas, KS = Kaposi sarcoma.
3.2. Clinical features of the patients
Common symptoms in KS patients were pain, itching and limb edema. Pain was the most common symptom accompanying KS patients, followed by enlarged lymph nodes. In terms of tumor location, the most common site was the foot, with approximately 59% of patients involving foot lesions, followed by the lower limbs (31%), hands (25%), upper limbs (19%), trunk (22%), face and neck (13%), and mouth (6%). The proportion of AIDS-KS patients with lesions on the trunk, head, face and neck, and oral cavity was higher than that of cKS patients (Table 1). Especially with oral lesions, the proportion of AIDS-KS patients was radically higher than cKS. The skin lesions of AIDS-KS patients were more likely to involve multiple sites and were more diffuse. Organs were involved in 4 of 22 cKS patients (1 involved intestinal tract, another for liver, the other 2 cases were lymph node and lung involvement respectively). Three of 10 patients with AIDS-KS had visceral organ involvement (1 involved intestinal tract, another for liver, the other involved lung). The incidence of involvement of internal organs was higher in patients with AIDS-KS than cKS. Patients with cKS and AIDS-KS were most often in stage III, followed by stage II. The proportion of AIDS-KS patients with stage IV (30%) was higher than that of cKS patients (18%). In all cases, 1 patient was infected with HHV-8.
3.3. Changes in CD4 + T lymphocytes
The median CD4 + T lymphocytes/mm3 of AIDS-KS patients before and after chemotherapy was 260 cells/mm3 and 510 cells/mm3 respectively.
3.4. Patients treatment outcome
3.4.1. Treatment of classic Kaposi sarcoma.
Of the 22 cKS patients, 19 cases (staged stage II–IV) underwent immunotherapy combined with chemotherapy, the other 3 patients with stage I underwent radiotherapy. The median course of chemotherapy was 4 (2–6). After treatment, 13 patients with CR, 4 patients with PR, 3 patients with SD, 2 patients with PD, and the total effective rate was 77 percent.
3.4.2. Treatment of AIDS-related Kaposi sarcoma.
10 patients (stage II–IV) underwent chemotherapy (2–6 cycles) with antiretroviral. After treatment, 5 patients were CR, 2 patients with PR, 1 patients with SD, 2 patients with PD, the total effective rate was 70 percent.
3.5. Survival outcome
Thirty-two patients were followed up until February 2023, and 2 were lost to follow-up. The percentage of loss to follow-up was 6.25 percent. The median follow-up months was 28 months (18–60 months). To the end of follow-up, in patients with cKS, 2 patients died. One died of cerebral hemorrhage, another died of disease progression. Among patients with AIDS-KS, 2 patients died of pulmonary infection. The median OS for cKS and AIDS-KS respectively were 56 and 50.8 months (P > .05, Fig.2).
Figure 2.
The five-year overall survival (A) cKS (B) AIDS-KS. AIDS = acquired immunodeficiency syndrome, AIDS-KS = Kaposi sarcomas linked to AIDS, cKS = classic Kaposi sarcomas, KS = Kaposi sarcoma.
3.6. Adverse effects related to the treatment
During therapy, III to IV grade myelosuppression occurred in 24 patients. With normalization of leucocytes after administration of human granulocyte colony-stimulating factor. Adverse reactions of the digestive system, such as nausea and vomiting, occurred in 29 patients.
4. Discussion
Kaposi sarcoma is a multifocal vascular proliferative tumor characterized by spindle cell proliferation and angiomatous structure. KS was first described in 1872 as a tumor of the lower limbs commonly found in older men, the disease is common in the Mediterranean region and among Jews of German and is known as classic KS,[7] in addition to classical KS, there are African (common in men and children in Central Africa), iatrogenic (mainly in transplant patients and associated with long-term use of immunosuppressive drugs), and AIDS-related KS.[8] The advent of antiretroviral combination therapy has greatly reduced the incidence of Kaposi sarcoma in AIDS patients. The pathogenesis of KS may be related to KSHV. According to the International Committee on Taxonomy of Viruses, the official name of KSHV is HHV-8.[9] The highest seropositivity of HHV-8 was found in Africa and Amazon region of Brazil (>50%), in contrast, North America and Asia have a lower rate of HHV-8 seropositivity (<5%).[10] Geographical differences in HHV-8 positivity also explain differences in the prevalence of KS in different regions. Previous study have reported that the positive rate of HHV-8 in Xinjiang Uygur Autonomous Region is remarkably higher than that in other parts of China.[11] But in our study, the rate of HHV-8 positivity was not high, with only 1 case of HHV-8 positivity. In the Mediterranean region, 0.03% of HHV-8-infected men over 50 years developed cKS, while 0.01 to 0.02% of HHV-8-infected women over 50 years developed cKS.[12] HHV-8 is an important causative factor in KS and other factors affecting tumourigenesis include hypoxia, epigenetic modifications, immunosuppression and hyperglycemia. HHV-8 supports both angiogenesis and cell proliferation, the 2 main histological features of Kaposi sarcoma.[13] Genetic predisposition can increase the risk for a KSHV-infected individual to develop KS. The genetic defects all appear to compromise an efficient T-cell response to KSHV, indicating that genetically determined, as well as iatrogenic (for posttransplant KS) and infection-related (for AIDS-KS) T-cell defects can predispose to KS development. In addition, a mutation altering the protein sequence of STAT4 was identified in a family in which 5 members, most of them women, developed classic KS at an advanced age.[14] Although HHV-8 is an important causative factor for KS, the positivity rate of HHV-8 was not high in this study. It may be related to the small sample size.
There is a markedly difference in the proportion of KS between males and females, males have a higher incidence than females.This was similar to the primary tumor profile found in our study. cKS is a geriatric disease, researchers in the United States and Europe reported that the median age at diagnosis was about 70 years, that only 4% to 8% of patients were under the age of 50, AIDS-KS patients are younger than cKS.[15] In our research, the mean age of cKS patients was 60 years (33–81 years) and the mean age of AIDS-KS patients was 50 years (25–75 years), which is generally consistent with other reports.
KS lesions typically involve the skin or mucosal surfaces. They are purplish, reddish blue or dark brown/black macules, plaques, and nodules that may bleed and ulcerate easily. With extensive spread, KS lesions may become cosmetically disfiguring and associated with lymphedema, pain, and secondary infection. In this study, cKS lesions were most commonly found on the foot, while oral lesions were higher in patients with AIDS-KS, AIDS-KS tend to involve multiple organs simultaneously, but cKS mostly involve only a single organ. In previous studies, the lower extremity and foot were the most common locations for cKS and AIDS-KS,[11] in our study, cKS lesions were more limited, whereas AIDS-KS lesions were more extensive.
As KS manifests in many forms, therapies should also be divided into multiple application scenarios. The goal of KS specific therapy in all patients with KS is symptom palliation and improved quality of life. State of the art combination antiretroviral therapy (cART) and monitoring of its efficacy are essential in the treatment of AIDS-KS. Cytotoxic chemotherapy represents the standard of care for KS. Consequently, cART combined with chemotherapy is the preferred regimen for AIDS-KS. In this study, 10 patients with AIDS-KS were treated with cART combination chemotherapy, 5 patients were CR, 2 patients with PR, the total effective rate was 70 percent, CD4 + T lymphocytes were higher than before. When the body is infected with HIV, the HIV virus destroys the body’s CD4 + T lymphocytes, resulting in a decrease in the number and function of CD4 + T lymphocytes, and eventually the development of AIDS. The occurrence of opportunistic infections or tumors is one of the hallmarks of AIDS patients and is also a major cause of death in AIDS patients. After chemotherapy with cART, the number of CD4 + T lymphocytes in AIDS-KS patients increased significantly. Chemotherapy combined with cART can control tumor progression, on the other hand, improve the immune status of patients and delay the disease process in AIDS.
Chemotherapy regimens include liposomal doxorubicin, which were currently recommended by the 2021 NCCN guidelines for patients with KS. liposomal doxorubicin is a formulation of the anthracycline doxorubicin in which the drug is encapsulated in PEG-coated liposomes. This alters the pharmacokinetic properties of doxorubicin, prolonging circulation time and enhancing localization to tumors. Liposomal doxorubicin is one of the best chemotherapeutic options for KS, due to its high antitumor effect and low toxicity in nontarget organs.[16] Interferon-alpha was evaluated in patients with classic Kaposi sarcoma was evaluated in 71% of patients with very good partial response rates, and was used for classic Kaposi sarcoma as routine treatment.[17] Little reported that thalidomide had a significant anti-KS response in a significant proportion of patients in a clinical study, demonstrating the clinical relevance of thalidomide in the treatment of KS.[18] In our research, 22 cases of cKS, 19 cases underwent chemotherapy combined with interferon-alpha, prednisone, thalidomide, 3 patients with stage I underwent radiotherapy. An overall efficiency was 77%. In 10 patients with AIDS-KS, the total effective rate was 70%. Both groups were treated with a chemotherapy-based regimen (same chemotherapy) and there was no significant difference in the overall efficiency between the 2 groups. Hengge et al[19]reported that long-term use of liposomal doxorubicin was safe, with a clinical benefifit of 85% in AIDS-KS. In our study, the overall effectiveness of chemotherapy combined with prednisone, interferon and thalidomide in cKS and AIDS-KS was not as high as reported in previous literature. Our low treatment efficacy may be related to the older age of the patients in this study.
The major adverse effect of chemotherapy in both groups was grade III to IV myelosuppression, Leukocytes were got to normal after administration of human granulocyte colony-stimulatin factor. With the continuous research on the pathogenesis of KS, many new drugs such as angiogenesis inhibitors, tyrosine kinase inhibitors and matrix metalloproteinases (MMP) inhibitors are being used in the clinical treatment of KS. MMP are highly expressed in KS lesions and may contribute to angiogenesis via degradation of extracellular matrix. A Phase II study of the MMP inhibitor COL-3 demonstrated a 41% overall response rate.[20] More new drugs will be available in the future for the treatment of KS.
The prognosis of Kaposi sarcoma is closely related to the clinical classification. Classic Kaposi sarcoma is a slow-growing tumor of low malignant potential. In this study, to the end of follow-up, the medain OS of AIDS-KS and cKS was not different (50.8 and 56 months). Hence, a good prognosis can also be achieved for AIDS-KS patients with antiviral combination chemotherapy. Two patients with AIDS-KS died of pulmonary infection. One study reported that AIDS-cKS were poorly treated and cause death.[11] However, in this study, the low mortality rate of AIDS-cKS may be related to cART combined chemotherapy treatment. The first principle of treatment for patients with AIDS-KS is to control their primary disease and to provide effective antiviral therapy (viral load reduction and CD4 + lymphocyte increase) in order to better control KS. Patients with AIDS-KS should be monitored for changes in CD4 + T lymphocyte counts and aggressive prevention of infections in the lung and other organs.
The mechanisms of KS are not yet fully understood and need to be further investigated and discussed. As a large number of molecular pathways and mechanisms of action are being elucidated, many new drugs and methods are gradually being applied for the treatment of KS.[21] The specific efficacy and potential adverse effects of these drugs remain to be seen and require more in-depth clinical studies to prove.
5. Conclusion
Kaposi Sarcoma will continue to be seen in people living with HIV/AIDS. It remains the most common cancer in regions that were endemic for KSHV. But the prognosis for KS is good, treatment can improve the patient’s prognosis. In the future, an improved understanding of KSHV-mediated oncogenesis is providing opportunities for development of targeted and immune-modulatory treatment approaches in each of the major KSHV-associated malignancies that employ small molecules or monoclonal antibodies.
Author contributions
Conceptualization: Feng He.
Data curation: Aibibai Jielili, Zhi Yong Cui, Hai Tao Guo.
Investigation: Hong Liang Yang.
Resources: Zhi Rong Zhang, Jin Hua Wang.
Writing – original draft: Hong Liang Yang.
Abbreviations:
- AIDS
- acquired immunodeficiency syndrome
- AIDS-KS
- Kaposi sarcomas linked to AIDS
- cART
- combination antiretroviral therapy
- cKS
- classic Kaposi sarcomas
- CR
- complete response
- HHV-8
- human herpesvirus type 8
- HIV
- human immunodeficiency virus
- KS
- Kaposi sarcoma
- KSHV
- Kaposi sarcoma associated herpesvirus
- MMP
- matrix metalloproteinases
- OS
- overall survival
- PD
- progressive diseases
- PR
- partial response
- SD
- stable disease
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Funding Funded by Tianjin Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A).
The article was a retrospective study and had been approved by the Medical Ethics Committee of People’s Hospital of Hotan District, Xinjiang Uygur Autonomous Region (approval no. 2022009).
The authors have no conflicts of interest to disclose.
How to cite this article: Yang HL, He F, Jielili A, Zhang ZR, Cui ZY, Wang JH, Guo HT. A retrospective study of Kaposi’s sarcoma in Hotan region of Xinjiang, China. Medicine 2023;102:41(e35552).
Contributor Information
Feng He, Email: heaven@tju.edu.cn.
Zhi Rong Zhang, Email: 2524505648@qq.com.
Zhi Yong Cui, Email: cuizhiyong1972@163.com.
Jin Hua Wang, Email: 3354798507@qq.com.
Hai Tao Guo, Email: 1298974656@qq.com.
References
- [1].Simard EP, Pfeiffer RM, Engels EA. Cumulative incidence of cancer among individuals with acquired immunodeficiency syndrome in the United States. Cancer. 2011;117:1089–96. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [2].Jemal A, Bray F, Forman D, et al. Cancer burden in Africa and opportunities for prevention. Cancer. 2012;118:4372–84. [DOI] [PubMed] [Google Scholar]
- [3].Chang Y, Ziegler J, Wabinga H, et al. Kaposi’s sarcoma-associated herpesvirus and Kaposi’s sarcoma in Africa. Uganda Kaposi’s sarcoma study group. Arch Intern Med. 1996;156:202–4. [PubMed] [Google Scholar]
- [4].Iftode N, Rădulescu MA, Aramă SS, et al. Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8)-review. Rom J Intern Med. 2020;58:199–208. [DOI] [PubMed] [Google Scholar]
- [5].David HM, Mutsvunguma LZ, Jennifer T, et al. A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits. Vaccine. 2019;37:4184–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Celeste L, Garbe C, Stratigos AJ, et al. Diagnosis and treatment of Kaposi’s sarcoma: European consensusbased interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019;114:117–27. [DOI] [PubMed] [Google Scholar]
- [7].Kaloterakis A, Papasteriades C, Filiotou A, et al. HLA in familial and nonfamilial Mediterranean Kaposi’s sarcoma in Greece. Tissue Antigens. 1995;45:117–9. [DOI] [PubMed] [Google Scholar]
- [8].Charlotte W-G, Forbes HJ, Elizabeth W, et al. Human herpesvirus infections and dementia or mild cognitive impairment: a systematic review and meta-analysis. Sci Rep. 2019;9:4743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Rachele B, Landis JT, An H. Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci USA. 2018;115:E11379–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Vangipuram R, Tyring SK. Epidemiology of Kaposi sarcoma: review and description of the nonepidemic variant. Int J Dermatol. 2019;58:538–42. [DOI] [PubMed] [Google Scholar]
- [11].Wu XJ, Pu XM, Kang XJ, et al. One hundred and five Kaposi sarcoma patients: a clinical study in Xinjiang, Northwest of China. J Eur Acad Dermatol Venereol. 2014;28:1545–52. [DOI] [PubMed] [Google Scholar]
- [12].Schwartz RA, Micali G, Nasca MR, et al. Kaposi sarcoma: a continuing conundrum. J Am Acad Dermatol. 2008;59:179–206; quiz 207–8. [DOI] [PubMed] [Google Scholar]
- [13].Dupin N. Update on oncogenesis and therapy for Kaposi sarcoma. Curr Opin Oncol. 2020;32:122–8. [DOI] [PubMed] [Google Scholar]
- [14].Mervi A, Kaasinen E, Nieminen JK, et al. 2015 Whole-genome sequencing identifies STAT4 as a putative susceptibility gene in classic Kaposi sarcoma. J Infect Dis. 2015;211:1842–51. [DOI] [PubMed] [Google Scholar]
- [15].David S, Bessaoud F, Meftah N, et al. A comparative study of classic and HIV-viremic and aviremic AIDS Kaposi sarcoma. AIDS. 2021;35:399–405. [DOI] [PubMed] [Google Scholar]
- [16].Ramya R, Uldrick TS, Polizzotto MN, et al. A pilot study of liposomal doxorubicin combined with bevacizumab followed by bevacizumab monotherapy in patients with advanced Kaposi Sarcoma. Clin Cancer Res. 2019;25:4238–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Isabelle R, Catherine L, Régine D, et al. Interferon therapy for Kaposi sarcoma associated with acquired immunodeficiency syndrome: still a valid treatment option? AIDS Patient Care STDS. 2013;27:537–8. [DOI] [PubMed] [Google Scholar]
- [18].Little RF, Wyvill KM, Pluda JM, et al. Activity of thalidomide in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 2000;18:2593–602. [DOI] [PubMed] [Google Scholar]
- [19].Hengge UR, Esser S, Rudel HP, et al. Long-term chemotherapy of HIV-associated Kaposi’s sarcoma with liposomal doxorubicin. Eur J Cancer. 2001;37:878–83. [DOI] [PubMed] [Google Scholar]
- [20].Bruce JD, Krown SE, Lee JY, et al. Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi’s sarcoma: an AIDS Malignancy Consortium Study. J Clin Oncol. 2006;24:1389–94. [DOI] [PubMed] [Google Scholar]
- [21].Mani R, Reza V, Hourvash H. Kaposi sarcoma after allogeneic hematopoietic stem cell transplant: a rare complication. Exp Clin Transplant. 2021;19:173–5. [DOI] [PubMed] [Google Scholar]