Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial.

BACKGROUND: Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. METHODS: In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. FINDINGS: 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. INTERPRETATION: Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.

The Contribution of Kaposi's Sarcoma-Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus-Infected Patients Being Investigated for Tuberculosis in South Africa.

BACKGROUND: Despite increasing numbers of human immunodeficiency virus (HIV)-infected South Africans receiving antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of mortality. Approximately 25% of patients treated for TB have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi's sarcoma-associated herpesvirus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for TB. METHODS: Six hundred eighty-two HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for TB, and followed for 12 weeks. KSHV serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated. RESULTS: Median CD4 count was 62 (range, 0-526) cells/µL; KSHV seropositivity was 30.7% (95% confidence interval [CI], 27%-34%); 5.8% had detectable KSHV-VL (median, 199.1 [range, 13.4-2.2 × 106] copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted odds ratio, 6.5 [95% CI, 1.3-32.4]) in patients without TB or other microbiologically confirmed coinfections (n = 159). Six patients had "possible KSHV-inflammatory cytokine syndrome" (KICS): 5 died, representing significantly worse survival (P < .0001), and 1 patient was diagnosed with KSHV-associated multicentric Castleman disease at autopsy. CONCLUSIONS: Given the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed TB, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.

Survival from childhood cancers in Eastern Africa: A population-based registry study.

Cancers occurring in children in Africa are often underdiagnosed, or at best diagnosed late. As a result, survival is poor, even for cancers considered 'curable'. With limited population-level data, understanding the actual burden and survival from childhood cancers in Africa is difficult. In this study, we aimed at providing survival estimates for the most common types of cancers affecting children aged 0-14 years, in three population-based Eastern African registries; Harare, Zimbabwe (Kaposi sarcoma, Wilms tumour (WT), non-Hodgkin lymphoma (NHL), retinoblastoma, and acute lymphocytic leukaemia (ALL)), Kampala, Uganda (Burkitt lymphoma, Kaposi sarcoma, WT, and retinoblastoma), and Nairobi, Kenya (ALL, retinoblastoma, WT, Burkitt lymphoma, and Hodgkin lymphoma). We included cases diagnosed within the years 1998-2009 and followed up till the end of 2011. We estimated the observed and relative survival at 1, 3, and 5 years after diagnosis. We studied 627 individual patient records. Median follow-up ranged from 2.2 months for children with Kaposi sarcoma in Harare to 30.2 months for children with ALL in Nairobi. The proportion of children lost to follow-up was highest in the first year after diagnosis. In Harare and Kampala, the 5-year relative survival was <46% for all cancer types. The 5-year relative survival was best for children in Nairobi, though with wider confidence intervals. Survival from childhood cancers in Africa is still poor, even for cancers with good prognosis and potential for cure. Supporting cancer detection, treatment, and registration activities could help improve survival chances for children with cancers in Africa.

Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children.

BACKGROUND: Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. METHODS: Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FINDINGS: Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. CONCLUSION: Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

[Profile of Kaposi sarcoma patients in the competence network HIV/AIDS]. / Profil der Kaposi-Sarkom-Patienten im Kompetenznetz HIV/AIDS.

BACKGROUND: Kaposi's sarcoma (KS) represents the most common AIDS-defining neoplasm. Only very few studies regarding the course and treatment of human immunodeficiency virus (HIV)-associated KS have been carried out in Germany. OBJECTIVE: In this study the course of HIV-associated KS was observed in patients from the cohort database of the competence network for HIV/AIDS. MATERIAL AND METHODS: Data from HIV-associated KS patients from 9 German core centers from 1987 to 2011 were retrospectively collected. Kaplan-Meier curves for the recurrence and survival probability were calculated. RESULTS: In 222 patients KS was diagnosed at a median age of 38.5 ± 10.1 years. Men were almost exclusively affected (97.7%). The HIV viral load at the time of diagnosis was in 7.4% <50 copies/ml. Of the patients 55.5% developed KS with a CD4 cell count of <200 cells/µl and 9.5% with >500 cells/µl. In 68 patients KS therapy consisted exclusively of the optimization or initiation of antiretroviral therapy (ART). In addition, 71 patients were treated with pegylated liposomal doxorubicin. During the median follow-up period of 8.9 ± 4.9 years, 80.2% of the patients were free of KS recurrence. Survival rates after 5 and 10 years were 96.8% and 91.3%, respectively. CONCLUSION: Even with a good immune status HIV-associated KS occurred. An effective ART was the most important mainstay of therapy. With appropriate therapy, HIV-positive patients with KS showed a good survival rate.

Updating vital status by tracking in the community among patients with epidemic Kaposi sarcoma who are lost to follow-up in sub-Saharan Africa.

BACKGROUND: Throughout most of sub-Saharan Africa (and, indeed, most resource-limited areas), lack of death registries prohibits linkage of cancer diagnoses and precludes the most expeditious approach to determining cancer survival. Instead, estimation of cancer survival often uses clinical records, which have some mortality data but are replete with patients who are lost to follow-up (LTFU), some of which may be caused by undocumented death. The end result is that accurate estimation of cancer survival is rarely performed. A prominent example of a common cancer in Africa for which survival data are needed but for which frequent LTFU has precluded accurate estimation is Kaposi sarcoma (KS). METHODS: Using electronic records, we identified all newly diagnosed KS among HIV-infected adults at 33 primary care clinics in Kenya, Uganda, Nigeria, and Malawi from 2009 to 2012. We determined those patients who were apparently LTFU, defined as absent from clinic for ≥90 days at database closure and unknown to be dead or transferred. Using standardized protocols which included manual chart review, telephone calls, and physical tracking in the community, we attempted to update vital status amongst patients who were LTFU. RESULTS: We identified 1222 patients with KS, of whom 440 were LTFU according to electronic records. Manual chart review revealed that 18 (4.1%) were classified as LFTU due to clerical error, leaving 422 as truly LTFU. Of these 422, we updated vital status in 78%; manual chart review was responsible for updating in 5.7%, telephone calls in 26%, and physical tracking in 46%. Among 378 patients who consented at clinic enrollment to be tracked if they became LTFU and who had sufficient geographic contact/locator information, we updated vital status in 88%. Duration of LTFU was not associated with success of tracking, but tracking success was better in Kenya than the other sites. CONCLUSION: It is feasible to update vital status in a large fraction of patients with HIV-associated KS in sub-Saharan Africa who have become LTFU from clinical care. This finding likely applies to other cancers as well. Updating vital status amongst lost patients paves the way towards accurate determination of cancer survival.

Outcome of second kidney transplantation in patients with previous post-transplantation Kaposi's sarcoma: A French retrospective study.

This retrospective study concerned 8 patients with post-transplantation Kaposi's sarcoma (pt-KS) after a first kidney transplant who later had a second kidney transplantation. Pt-KS was widespread, with lymph node or visceral involvement in 7 cases. Complete remission was observed in 6 cases and partial remission in 2. After the second kidney transplantation, only 2 cases showed recurrence of skin KS, one with previous complete remission of KS and one with partial remission. The mean delay between stability or complete remission of KS and retransplantation was 2.0 and 7.3 years in patients with and without relapse, respectively. Both recurrent cases showed complete KS remission after tapering immunosuppression therapy and/or switching a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. We compared these 8 cases to 24 controls who had undergone 2 kidney transplantations but did not have KS, matching on sex, age and phototype. Cases and controls did not differ in graft function or survival. A second kidney transplantation may be possible after pt-KS and has acceptable risk, especially after a long complete remission of pt-KS.

Long-term outcome for kaposiform hemangioendothelioma: A report of two cases.

Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular tumor of skin and deep soft tissues that typically presents in infancy and may be associated with a potentially life-threatening coagulopathy known as Kasabach-Merrit phenomenon (KMP). Recent advances in medical therapy have successfully treated many patients. However, our knowledge regarding the natural history of these lesions and optimum surveillance strategies remains rudimentary. We report two young women who had KHE with KMP treated in infancy and presented in adolescence with comorbidities related to their KHE tumor. This presentation supports the need for long-term surveillance in these patients.

Trends in Malignancies among Korean Patients Infected with Human Immunodeficiency Virus in the Highly Active Antiretroviral Therapy Era.

Since the introduction of highly active antiretroviral therapy, the life span of people with human immunodeficiency virus (HIV) or AIDS (PWHA) has been extended significantly. Therefore, the importance of non-AIDS-defining cancers (NADCs), as well as AIDS-defining cancers (ADCs) has increased. There is little information concerning the epidemiology of malignancies in PWHA in Korea. A descriptive epidemiologic study was conducted at a tertiary care hospital in Korea. PWHA who visited Pusan National University Hospital from January 2000 to October 2014 were included. Demographics and clinical data were obtained from the medical records and analyzed. A total of 950 PWHA were observed for 4,439.71 person-years. Forty-eight episodes (5.05%) of cancers were diagnosed in 47 patients. Mean age of the enrolled patients was 40.66 ± 12.15 years and 88% were male. Among the 48 cancer episodes, 20 (42%) were ADCs and 28 were NADCs. The most common ADCs was non-Hodgkin's lymphoma (53.6%), followed by Kaposi's sarcoma (17.9%). The most common NADCs were lung cancer (25%) and hepatocellular carcinoma (25%). The overall incidence of total cancers, ADCs, and NADCs was 10.8 (95% confidence interval [CI], 8.0-14.3), 4.5 (95% CI, 2.8-7.0), and 6.3 (95% CI, 4.2-9.1)/1,000 person-years, respectively. NADCs accounted for 12/15 (80%) of cancers among PWHA with good adherence to care. The 5-year survival rate of PWHA and NADC was 26.3%. NADCs have become the main type of malignancy among Korean PWHA with good adherence to care. Effective strategies to improve screening of NADCs among PWHA are required in Korea.

Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS).

BACKGROUND: Kaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory cytokine syndrome (KICS) distinct from KSHV-MCD was reported. METHODS: We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection. RESULTS: All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50-74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6-11), median grade of worst symptom 3 (2-4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death. CONCLUSIONS: KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted.

Effect of Non-Hodgkin Lymphoma on Survival in Patients With Malignant Fibrous Histiocytoma, Kaposi Sarcoma, and Sebaceous Carcinoma: A SEER Population-Based Study.

OBJECTIVE: To quantify the behavior of dermatofibrosarcoma protuberans (DFSP), malignant fibrous histiocytoma (MFH), Kaposi sarcoma (KS), and sebaceous carcinoma (SC) in patients with a history of non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Subjects with a diagnosis of DFSP, MFH, KS, or SC between 1990 and 2006 were identified in the Surveillance, Epidemiology, and End Results Program database. For each skin cancer type, the standardized mortality ratio (SMR) for death due to any cause and death due to skin cancer was estimated. RESULTS: From 1990 through 2006, 25,357 skin cancers were identified: 4,192 DFSP, 6,412 MFH, 10,543 KS, and 4,222 SC. For patients with a history of non-CLL NHL, SMRs for death due to any cause were 1.45 (95% confidence interval [CI], 1.03-2.04; p = 0.04) for MFH, 2.90 (95% CI, 2.50-3.36; p < 0.001) for KS, and 3.25 (95% CI, 1.84-5.75; p < 0.001) for SC and SMRs for death due to skin cancer were 0.55 (95% CI, 0.23-1.31; p = 0.18) for MFH, 2.93 (95% CI, 2.49-3.43; p < 0.001) for KS, and 4.07 (95% CI, 1.28-12.94; p < 0.001) for SC. CONCLUSION: Among patients with KS and SC, patients with a history of non-CLL NHL have a greater risk of overall and cause-specific death than expected.

Mortality Risk After AIDS-Defining Opportunistic Illness Among HIV-Infected Persons--San Francisco, 1981-2012.

OBJECTIVE: To examine whether improved human immunodeficiency virus (HIV) treatment was associated with better survival after diagnosis of AIDS-defining opportunistic illnesses (AIDS-OIs) and how survival differed by AIDS-OI. DESIGN: We used HIV surveillance data to conduct a survival analysis. METHODS: We estimated survival probabilities after first AIDS-OI diagnosis among adult patients with AIDS in San Francisco during 3 treatment eras: 1981-1986; 1987-1996; and 1997-2012. We used Cox proportional hazards models to determine adjusted mortality risk by AIDS-OI in the years 1997-2012. RESULTS: Among 20 858 patients with AIDS, the most frequently diagnosed AIDS-OIs were Pneumocystis pneumonia (39.1%) and Kaposi sarcoma (20.1%). Overall 5-year survival probability increased from 7% in 1981-1986 to 65% in 1997-2012. In 1997-2012, after adjustment for known confounders and using Pneumocystis pneumonia as the referent category, mortality rates after first AIDS-OI were highest for brain lymphoma (hazard ratio [HR], 5.14; 95% confidence interval [CI], 2.98-8.87) and progressive multifocal leukoencephalopathy (HR, 4.22; 95% CI, 2.49-7.17). CONCLUSIONS: Survival after first AIDS-OI diagnosis has improved markedly since 1981. Some AIDS-OIs remain associated with substantially higher mortality risk than others, even after adjustment for known confounders. Better prevention and treatment strategies are still needed for AIDS-OIs occurring in the current HIV treatment era.

[Historical Review of Kaposi sarcoma in pre-HAART era: evolution with different chemotherapy schedules and remission with ganciclovir use]. / Revisión histórica del sarcoma de Kaposi en la era pre-TARAA (terapia antirretroviral altamente activa): evolución con diferentes esquemas de quimioterapia y remisión con el uso de ganciclovir.

Ganciclovir has shown in vitro anti-human herpesvirus-8 activity, Kaposi sarcoma agent. We analyzed all Kaposi sarcoma patients from 1985 to 1996 pre-HAART era and identified Kaposi sarcoma/AIDS patients who achieved complete remission prior to HAART use. RESULTS: We saw 155 Kaposi sarcoma patients up to 1996, 150 with enough information, only 12 received ganciclovir, eight of them for ≥ 21 days; four died within 16 weeks of ganciclovir administration. We identified four male patients with extensive Kaposi sarcoma with complete remission achieved after ganciclovir for CMV end-organ disease. Complete remission was achieved (9, 5, 10 and 5 months) after ganciclovir, which persisted even after antiretroviral therapy failure. All received two nucleosides and indinavir was later added with irregular compliance. The CD4 counts when ganciclovir was started: 11 (4%), 60 (5%), 127 (14%), and 38 (3%) and when they achieved complete remission: 37 (4%), 109 (9%), 313 (13%) and 136 (9%), respectively. Two patients died with no Kaposi sarcoma relapse three years later, with wasting syndrome and other pulmonary-embolism seven years later. One was lost to follow-up in complete remission in the year 2000, the other was alive in 2014 with 27% 820 CD4 cells/ml. The use of ganciclovir was statistically significantly associated with Kaposi sarcoma remission p = 0.001. CONCLUSIONS: Ganciclovir use was associated to complete remission of Kaposi sarcoma in the pre-HAART era.

Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort.

Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997-2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001-2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992-1996) and early-cART (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001-2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era.

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/µL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly.

OBJECTIVE: To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis. STUDY DESIGN: An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Children's Hospital between 1995 and 2011. RESULTS: The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years). CONCLUSIONS: We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy.

Clinical characteristics and outcomes of HIV-infected children diagnosed with Kaposi sarcoma in Malawi and Botswana.

BACKGROUND: Kaposi sarcoma (KS) is the most common HIV-associated malignancy in sub-Saharan Africa. The presentation and outcomes of pediatric KS are not well understood. PROCEDURE: We performed a retrospective cohort analysis of 81 HIV-infected children with KS at the Baylor Children's Clinical Centres of Excellence in Malawi and Botswana from March 2003 to October 2009. RESULTS: Eighty-one children with KS were identified whose median age was 8.0 (inter-quartile range 5.1-11.3) years. KS lesions were presented primarily on the skin (83%), lymph nodes (52%), and oral mucosa (41%). Occasionally disease was limited to the lymph nodes only (10%). Severe immunosuppression (70%), anemia (29%), and thrombocytopenia (17%) were common laboratory findings. Highly active antiretroviral therapy (HAART) was administered to 94% of children, including 77% who received HAART plus chemotherapy. KS immune reconstitution inflammatory syndrome (IRIS) occurred in 22%. Disease status 12 months after KS diagnosis was determined for 69 children: 43% were alive and 57% had died. Severe immunosuppression was independently associated with mortality in multivariate analysis (OR = 4.3; 95% CI 1.3-14.6; P = 0.02). CONCLUSION: KS occurs in a significant number of HIV infected children in sub-Saharan Africa. Pediatric KS is distinct from KS in adults. Lymph node involvement was a common manifestation of KS in children, and severe immunosuppression was associated with the highest mortality risk. Though overall mortality was high in children with KS, patients did achieve clinical remission in settings with limited diagnostic and therapeutic resources.

Epidemiology of classic and AIDS-related Kaposi's sarcoma in the USA: incidence, survival, and geographical distribution from 1975 to 2005.

This study aimed to examine trends in incidence, geographical distribution, and survival of classic and AIDS-related Kaposi's sarcoma (KS) in the general US population using Surveillance, Epidemiology, and End Results (SEER) tumour registries with 12 066 patients diagnosed with KS between 1975 and 2005. Although the age-adjusted standardized incidence ratio (SIR) of AIDS-related KS (1·9) during 1980-2005 was not significantly higher than that of classic KS (1·4) during 1975-2005 (P = 0·78), the trends in annual SIR rates revealed distinct patterns. While the SIR for AIDS-related KS declined across all registries from the early 1990s (4·6) to late-1990s (0·3) (P = 0·05), the SIR of classic KS remained relatively steady (1·7). In both forms the SIR of KS was highest in metropolitan areas. The 5-year survival rates for patients with AIDS-related KS improved from 12·1% (1980-1995) to 54% (1996-2005) (P = 0·05). Survival rates for patients with classic KS remained stable, ranging from 75·7% to 88·6% during the 30-year period. These results may reflect improved HIV treatment.

Brain localization of Kaposi's sarcoma in a patient treated by combination antiretroviral therapy.

BACKGROUND: Central nervous system is a very rare site of Kaposi's sarcoma in acquired immunodeficiency syndrome. Kaposi's sarcoma, a neoplasm of endothelial origin, occurs mainly in the skin, but can involve many tissues, especially in patients with a poor immunity. Combination antiretroviral therapy, highly active against human immunodeficiency virus type-1, has caused a dramatic reduction of cutaneous and visceral involvements. No report of central nervous system localization of Kaposi's sarcoma is described since the introduction of combination antiretroviral therapy in the late 90's. CASE PRESENTATION: A 42 year-old Caucasian man affected by human immunodeficiency virus type-1 infection treated with combination antiretroviral therapy and showing relatively preserved immunity with low viral load presented gingival squamous cell carcinoma and visceral (lungs and lymph nodes) Kaposi's sarcoma. Chemotherapy and radiotherapy were performed with improvement of both neoplasms. Afterwards, a magnetic resonance imaging showed focal lesions of the brain. Despite new chemotherapy and radiotherapy the patient died. Histology after autopsy revealed brain lesions due to Kaposi's sarcoma with the detection of Human Herpesvirus 8 on tissue samples. CONCLUSIONS: This is the first report in the combination antiretroviral therapy era of a very rare complication of Kaposi's sarcoma, such as that of brain localization, in a patient with a relatively good control of human immunodeficiency virus infection. Therefore, Kaposi's sarcoma should be considered in differential diagnosis with other intracranial mass lesions that can occur in human immunodeficiency virus infected-patients focusing the issue of appropriate treatment for central nervous system involvement.

Electrochemotherapy in the treatment of Kaposi sarcoma cutaneous lesions: a two-center prospective phase II trial.

BACKGROUND: Electrochemotherapy (ECT) is an emerging treatment for cutaneous lesions of different tumor types. The combination of chemotherapy and electroporation enhances drug uptake into tumoral cells. However, its role in the treatment of Kaposi sarcoma (KS) has not yet been well defined, and to date, literature reports are scarce. We prospectively evaluated clinical activity and safety of ECT in KS patients. METHODS: Twenty-three patients with histologically confirmed unresectable KS, not treatable by radiotherapy or intralesional vincristine therapy, were enrolled onto the study according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines and treated with a pulse generator. RESULTS: A response to the first ECT session was obtained in all patients, with a complete response (CR) in 14 (60.9%) of 23 patients. A second ECT was performed in 5 (21.7%) and a third in 2, with a median interval between two sessions of 5.1 (range 2.5-25.5) months. Overall, a total of 15 patients (65%) experienced a CR. After a median follow-up of 1.5 years (range 2 months to 4.2 years), 16 patients maintained the response, 4 after repeated courses. Sustained local control of treated lesions was present in 20 of 23 patients. The overall survival rate was 74.4% at 2 years. CONCLUSIONS: ECT represents an additional therapeutic tool for the management of KS cutaneous lesions, characterized by a definite clinical activity and long-lasting remissions. The absence of systemic side effects and the low impact on the immune system also make this treatment suitable for elderly people, even with repeated courses.