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BACKGROUND: Breast cancer incidence in sub-Saharan Africa (SSA) is increasing, and SSA has the highest age-standardized breast cancer mortality rate worldwide. However, high-quality breast cancer data are limited in SSA. MATERIALS AND METHODS: We examined breast cancer patient and tumor characteristics among women in Lilongwe, Malawi and evaluated risk factor associations with patient outcomes. We consecutively enrolled 100 women ≥ 18 years with newly diagnosed, pathologically confirmed breast cancer into a prospective longitudinal cohort with systematically assessed demographic data, HIV status, and clinical characteristics. Tumor subtypes were further determined by immunohistochemistry, overall survival (OS) was estimated using Kaplan-Meier methods, and hazards ratios (HR) were calculated by Cox proportional hazard analyses. RESULTS: Of the 100 participants, median age was 49 years, 19 were HIV-positive, and 75 presented with late stage (III/IV) disease. HER2-enriched and triple-negative/basal-like subtypes represented 17% and 25% tumors, respectively. One-year OS for the cohort was 74% (95% CI 62-83%). Multivariable analyses revealed mortality was associated with HIV (HR, 5.15; 95% CI 1.58-16.76; p = 0.006), stage IV disease (HR, 8.86; 95% CI 1.07-73.25; p = 0.043), and HER2-enriched (HR, 7.46; 95% CI 1.21-46.07; p = 0.031), and triple-negative subtypes (HR, 7.80; 95% CI 1.39-43.69; p = 0.020). CONCLUSION: Late stage presentation, HER2-enriched and triple-negative subtypes, and HIV coinfection were overrepresented in our cohort relative to resource-rich settings and were associated with mortality. These findings highlight robust opportunities for population- and patient-level interventions across the entire cascade of care to improve breast cancer outcomes in low-income countries in SSA.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Humanos , Imuno-Histoquímica , Incidência , Estudos Longitudinais , Malaui/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Adulto JovemRESUMO
Kaposi sarcoma (KS) is among the most common childhood malignancies in central, eastern, and southern Africa. Although its unique clinical features have been established, biological mechanisms related to the causative agent, KS-associated herpes-virus (KSHV), have yet to be explored in children. We performed a prospective observational pilot study to explore associations between KSHV viral load (VL), human interleukin-6 (IL-6) and IL-10 levels, and clinical characteristics of 25 children with KS in Lilongwe, Malawi from June 2013-August 2015. The median age was 6.4 years. Lymphadenopathy was the most common site of KS involvement (64%), followed by skin and oral mucosa (44% each), woody edema (12%), and pulmonary (8%). Baseline samples for plasma KSHV VL, IL-6 and IL-10 analyses were available for 18/25 patients (72%) at time of KS diagnosis. KSHV VL was detectable at baseline in 12/18 (67%) patients, the median baseline IL-6 level was 8.53 pg/mL (range 4.31-28.33), and the median baseline IL-10 level was 19.53 pg/mL (range 6.91-419.69). Seven (39%) patients presented with an IL-6 level > 10 pg/mL (exceeding twice the upper limit of normal). Detectable KSHV VL was significantly associated with lymphadenopathic KS (p = 0.004), while having undetectable KSHV VL was associated with a higher likelihood of presenting with hyperpigmented skin lesions (p = 0.01). Detectable KSHV VL and elevated IL-6 levels are present in a subset of children with KS. Lytic activation of KSHV and associated elevation in KSHV VL may contribute to the unique clinical manifestations of pediatric KS in KSHV-endemic regions of Africa.
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Infecções por HIV/metabolismo , Infecções por Herpesviridae/metabolismo , Interleucina-6/metabolismo , Sarcoma de Kaposi/metabolismo , Carga Viral , Adolescente , Criança , Pré-Escolar , Doenças Endêmicas , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/fisiologia , Humanos , Lactente , Malaui/epidemiologia , Masculino , Projetos Piloto , Estudos Prospectivos , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/virologia , Ativação Viral/fisiologiaRESUMO
Outcomes for diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa (SSA) are poorly described. We report mature data from one of the first prospective SSA cohorts. Patients aged ≥18 years with DLBCL were enrolled in Malawi 2013-2017. Participants were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy and concurrent antiretroviral therapy (ART) if positive for human immunodeficiency virus (HIV+). Eighty-six participants (mean age 47 years, standard deviation 13) were enrolled: 54 (63%) were male and 51 (59%) were HIV+, of whom 34 (67%) were on ART at DLBCL diagnosis. Median CD4 count was 0·113 cells × 109 /l (interquartile range [IQR] 0·062-0·227) and 25 (49%) had HIV viral load <400 copies/µl. Participants received median six cycles CHOP (IQR 4-6). No patients were lost to follow-up and the 2-year overall survival was 38% (95% confidence interval 28-49). In multivariable analyses, Eastern Cooperative Oncology Group performance status (PS) ≥2 and lactate dehydrogenase (LDH) >2× upper limit of normal (ULN) were associated with mortality. HIV status was not associated with mortality. A simplified prognostic model of LDH >2× ULN and PS ≥2 performed at least as well as the age-adjusted International Prognostic Index. DLBCL can be successfully treated in SSA and outcomes did not differ by HIV status. A simplified prognostic model prognosticates well and may be easier to use in resource-limited settings but requires validation.
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Antirretrovirais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Soropositividade para HIV , HIV-1 , Linfoma Difuso de Grandes Células B , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/mortalidade , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Malaui/epidemiologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Prospectivos , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
BACKGROUND: Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype. However, an accurate understanding of melanoma in this part of the world is hindered by the very limited nature of prior publications. The aim of this study was to determine the epidemiological profile, anatomical distribution and histopathological features of melanoma presenting in Africans at a tertiary referral hospital in Malawi. METHODS: This is a retrospective study that characterized melanoma cases diagnosed from January 2012 to December 2017, at a cancer referral centre in Malawi. All confirmed, malignant melanoma cases during the study period were retrieved. Data abstracted included age, sex, anatomic site and whether it was a primary or metastatic site. Breslow thickness in millimetres, Clark level of invasion, presence of ulceration and melanoma subtype were also evaluated. RESULTS: One hundred thirty-two cases were included in the study, 81 (61%) were female and 26 (20%) were from a metastatic site. The mean age was 57 years (sd = 15) with the majority in the age group 60-69 years. Males presented at an older age than females. Ninety five percent of cutaneous melanomas were located on acral sites, most commonly the foot (87%) and the most common histopathological subtype was acral lentiginous. Eighty four percent presented with a Breslow thickness over 4 mm (median 9 mm). CONCLUSION: Our study shows that malignant melanoma occurs in black people in Malawi and may be an under-appreciated malignancy. While long term clinical follow-up was not available, most patients presented at late stages of the disease, supporting a poor prognosis. These results suggest that increased awareness of melanoma in black Africans and earlier intervention may have meaningful impacts on outcomes and survival.
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Point-of-care tools are needed in sub-Saharan Africa (SSA) to improve pediatric Burkitt lymphoma (BL) diagnosis and treatment. We evaluated plasma Epstein-Barr virus (pEBV) DNA as a pediatric BL biomarker in Malawi. Prospectively enrolled children with BL were compared to classical Hodgkin lymphoma (cHL) and nonlymphoma diagnoses. Pediatric BL patients received standardized chemotherapy and supportive care. pEBV DNA was measured at baseline, mid-treatment, and treatment completion. Of 121 assessed children, pEBV DNA was detected in 76/88 (86%) with BL, 16/17 (94%) with cHL, and 2/16 (12%) with nonlymphoma, with proportions higher in BL versus nonlymphoma (p < 0.001) and similar in BL versus cHL (p = 0.69). If detected, median pEBV DNA was 6.1 log10 copies/mL for BL, 4.8 log10 copies/mL for cHL, and 3.4 log10 copies/mL for nonlymphoma, with higher levels in BL versus cHL (p = 0.029), and a trend toward higher levels in BL versus nonlymphoma (p = 0.062). pEBV DNA declined during treatment in the cohort overall and increased in several children before clinical relapse. Twelve-month overall survival was 40% in the cohort overall, and for children with baseline pEBV detected, survival was worse if baseline pEBV DNA was ≥6 log10 copies/mL versus <6 log10 copies/mL (p = 0.0002), and also if pEBV DNA was persistently detectable at mid-treatment versus undetectable (p = 0.041). Among children with baseline pEBV DNA detected, viremia was the only significant risk factor for death by 12 months in multivariate analyses (adjusted hazard ratio 1.35 per log10 copies/mL, 95% CI 1.04-1.75, p = 0.023). Quantitative pEBV DNA has potential utility for diagnosis, prognosis, and response assessment for pediatric BL in SSA.
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Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/virologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Plasma/virologia , Biomarcadores Tumorais/genética , Linfoma de Burkitt/patologia , Criança , DNA Viral/genética , Infecções por Vírus Epstein-Barr/patologia , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Malaui , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Carga Viral/métodosRESUMO
BACKGROUND: Extranodal NK/T-cell lymphoma (ENKTCL) reports from sub-Saharan Africa (SSA) are remarkably rare, despite early childhood acquisition and high prevalence of the causative infectious agent, Epstein-Barr virus (EBV), and frequent occurrence of other lymphoproliferative disorders causally associated with EBV. CASE PRESENTATIONS: At a national teaching hospital in Malawi, three patients of African descent were seen with ENKTCL between 2013 and 2014. Patients were aged between 29 and 60 years, two with craniofacial involvement and one with a primary abdominal tumor, and all were HIV-negative. All had systemic B symptoms, and two severely impaired performance status. On histologic review, morphology and immunophenotyping demonstrated classical ENKTCL features in all cases, including diffuse proliferations of intermediate-to-large atypical lymphocytes with high mitotic activity and extensive background necrosis, positivity for CD3 and CD56, and negativity for CD20. By in situ hybridization, all three tumors were positive for EBV-encoded RNA (EBER). Baseline plasma EBV DNA was also markedly elevated for all three patients. Due to radiotherapy and chemotherapy limitations, patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with rapid disease progression. All three patients died from progressive lymphoma within 3 months of initial diagnosis. CONCLUSIONS: Our experience with these three patients in Malawi can highlight that ENKTCL does indeed occur in SSA, increase familiarity with ENKTCL among clinicians and pathologists throughout the region, and emphasize the need for better diagnosis and treatment for this neglected population.
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Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Ciclofosfamida/uso terapêutico , DNA Viral , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Imunofenotipagem/métodos , Linfoma Extranodal de Células T-NK/etiologia , Linfoma Extranodal de Células T-NK/metabolismo , Malaui , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. METHODS: We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. RESULTS: Among 31 patients with confirmed cHL, the median age was 19 years (range, 2-51 years) and 22 (71%) were male. Sixteen patients (52%) had stage III/IV, 25 (81%) B symptoms, and 16 (52%) performance status impairment. Twenty-three patients (74%) had symptoms >6 months, and 11 of 29 (38%) had received empiric antituberculosis treatment. Anemia was common with median hemoglobin 8.2 g/dL (range, 3.1-17.1 g/dL), which improved during treatment. No children and 5 of 15 adults (33%) were HIV+. All HIV+ patients were on antiretroviral therapy for a median 15 months (range, 2-137 months), with median CD4 count 138 cells/µL (range, 23-329 cells/µL) and four (80%) having undetectable HIV. EBV was present in 18 of 24 (75%) tumor specimens, including 14 of 20 (70%) HIV- and 4 of 4 (100%) HIV+. Baseline plasma EBV DNA was detected in 25 of 28 (89%) patients, with median viral load 4.7 (range, 2.0-6.7) log10 copies/mL, and subsequently declined in most patients. At 12 months, overall survival was 75% (95% confidence interval [CI], 55%-88%) and progression-free survival 65% (95% CI, 42%-81%). Baseline plasma EBV DNA and persistent viremia during treatment were associated with poorer outcomes. CONCLUSION: cHL in Malawi is characterized by delayed diagnosis and advanced disease. Most cases were EBV associated and one-third of adults were HIV+. Despite resource limitations, 12-month outcomes were good.
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Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/epidemiologia , Adolescente , Adulto , Contagem de Linfócito CD4 , Criança , Pré-Escolar , DNA Viral/sangue , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/complicações , Feminino , Infecções por HIV/complicações , HIV-1/genética , Herpesvirus Humano 4/genética , Doença de Hodgkin/complicações , Humanos , Estudos Longitudinais , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Carga Viral , Viremia/virologia , Adulto JovemRESUMO
Burkitt lymphoma (BL) is the most common paediatric cancer in sub-Saharan Africa (SSA). Anthracyline-based treatment is standard in resource-rich settings, but has not been described in SSA. Children ≤18 years of age with newly diagnosed BL were prospectively enrolled from June 2013 to May 2015 in Malawi. Staging and supportive care were standardized, as was treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for six cycles. Among 73 children with BL, median age was 9·2 years (interquartile range 7·7-11·8), 48 (66%) were male and two were positive for human immunodeficiency virus. Twelve (16%) had stage I/II disease, 36 (49%) stage III and 25 (34%) stage IV. Grade 3/4 neutropenia occurred in 17 (25%), and grade 3/4 anaemia in 29 (42%) of 69 evaluable children. Eighteen-month overall survival was 29% (95% confidence interval [CI] 18-41%) overall. Mortality was associated with age >9 years [hazard ratio [HR] 2·13, 95% CI 1·15-3·94], female gender (HR 2·12, 95% CI 1·12-4·03), stage (HR 1·52 per unit, 95% CI 1·07-2·17), lactate dehydrogenase (HR 1·03 per 100 iu/l, 95% CI 1·01-1·05), albumin (HR 0·96 per g/l, 95% CI 0·93-0·99) and performance status (HR 0·78 per 10-point increase, 95% CI 0·69-0·89). CHOP did not improve outcomes in paediatric BL compared to less intensive regimens in Malawi.
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Antraciclinas/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/mortalidade , Criança , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Malaui/epidemiologia , Masculino , Estadiamento de Neoplasias , Prednisona/uso terapêutico , Estudos Prospectivos , Fatores Sexuais , Resultado do Tratamento , Vincristina/uso terapêuticoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hiperplasia do Linfonodo Gigante/mortalidade , Infecções por HIV/complicações , HIV/isolamento & purificação , Adulto , Antirretrovirais , Estudos de Casos e Controles , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/virologia , Quimioterapia Combinada , Feminino , Seguimentos , HIV/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs.
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Introduction: Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by systemic inflammation, lymphadenopathy, and cytopenias. MCD caused by Kaposi sarcoma herpesvirus (MCD-KSHV) frequently arises in the context of HIV. It can be associated with immune reconstitution inflammatory syndrome (IRIS), but MCD-IRIS is rarely reported in sub-Saharan Africa (SSA) where HIV and KSHV infection are common. Case description: A 36-year-old woman in Malawi with HIV on antiretroviral therapy (ART) for nine years presented with fatigue, weight loss, and lymphadenopathy. Lymph node biopsy was consistent with HIV lymphadenitis without evident KSHV-MCD and HIV RNA was 4,244 copies/mL. She switched to second-line ART and returned four months later with worsening lymphadenopathy, fever, night sweats, weight loss, and anemia. A repeat lymph node biopsy demonstrated unequivocal KSHV-MCD features not present on the original biopsy. Her repeat HIV viral load was undetectable and she received chemotherapy with subsequent remission on continued ART for 24 months. Discussion: This is among the first reported cases of MCD-IRIS from SSA, which has implications for a region where HIV and KSHV are highly prevalent. MCD-IRIS may contribute to early mortality after ART initiation in SSA, and increased awareness alongside improved diagnostic and treatment capacity are needed.
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Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.
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Linfoma de Burkitt , Infecções por HIV , Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Antirretrovirais/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Malaui/epidemiologiaRESUMO
BACKGROUND: There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi. METHODS: This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per µL or higher (if HIV-positive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 109 cells per L or higher, a platelet count of 100 × 109 platelets per L or higher, a serum creatinine concentration of 132·60 µmol/L or less, a total bilirubin concentration of 34·21 µmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum 2 mg/m2), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710. FINDINGS: Between Aug 1, 2016, and July 31, 2019, 76 patients were screened, of whom 37 were eligible for the study and received R-CHOP. The median age of patients was 44 years (IQR 39-49) and 16 (43%) were women. Of all 37 patients, 20 (54%) had stage III or IV DLBCL, and the age-adjusted international prognostic index was 2 or higher in 25 (68%) patients. 27 (73%) patients were HIV-positive, with a median CD4 count of 208 cells per µL (IQR 144-422), and 21 (78%) patients were receiving ART at enrolment. Patients completed a median of six cycles (IQR 4-6). Grade 3 or 4 non-haematological toxic effects were reported in 12 (32% [95% CI 19-49]) patients, the most common of which was infection (nine [24%] patients). Of 16 (43%) deaths, ten were due to progression of DLBCL, four were due to treatment-related complications, and two were due to other causes, yielding a treatment-related mortality of 11% (95% CI 4-26%). Grade 3 or 4 neutropenia was observed in 26 (70%) patients, and grade 3 or 4 anaemia was observed in 11 (29%) patients. A total of 22 (59%) patients had a complete response. Overall survival was 68% (95% CI 50-80) at 12 months and 55% (37-70) at 24 months, and progression-free survival was 59% (42-73) at 12 months and 53% (35-68) at 24 months. INTERPRETATION: R-CHOP could be feasible, safe, and efficacious in patients with DLBCL in Malawi. This is the first completed clinical trial on DLBCL focused on sub-Saharan African populations. Given the paucity of data on treatment of DLBCL from this region, these results could inform emerging cancer treatment programmes in sub-Saharan Africa. FUNDING: The University of North Carolina Lineberger Comprehensive Cancer Center.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoAssuntos
Medula Óssea/patologia , Eosinófilos/patologia , Linfoma/patologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Contagem de Leucócitos , Linfoma/sangue , Malaui , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto JovemRESUMO
Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA.
Assuntos
Biomarcadores Tumorais/sangue , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por HIV/complicações , Herpesvirus Humano 4/genética , Linfoma Relacionado a AIDS/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , DNA Viral/genética , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , HIV/isolamento & purificação , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma Relacionado a AIDS/sangue , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/virologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/virologia , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Aggressive non-Hodgkin lymphoma (NHL) is among the most common cancers in sub-Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16-63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9-460), and nine (82%) had suppressed HIV RNA < 400 copies/mL. Patients received a median of six cycles (range 2-8) and median follow-up was 14 months (range 2-34) among patients still alive. Grade 3/4 neutropenia was observed in 26% of cycles and in 65% of patients. Sixteen (94%) responded to EPOCH and 10 (59%) achieved a complete response. One-year overall survival (OS) was 62% (95% confidence interval [CI], 42%-91%). Five patients (29%) died from progressive NHL and three (18%) from treatment-related complications. These data suggest EPOCH with setting-appropriate modifications may be a practical, safe, and effective option for improving high-risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infecções por HIV/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Neutropenia/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Contagem de Linfócito CD4 , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/mortalidade , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Intervalo Livre de Progressão , RNA Viral/sangue , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
Purpose Cancer surveillance provides a critical evidence base to guide cancer control efforts, yet population-based coverage in Africa is sparse. Hospital-based registries may help fill this need by providing local epidemiologic data to guide policy and forecast local health care needs. We report the epidemiology of patients with cancer recorded by a de novo hospital-based cancer registry at Kamuzu Central Hospital, Malawi, the sole provider of comprehensive oncology services for half the country and location of a high-volume pathology laboratory. Methods We conducted active case finding across all hospital departments and the pathology laboratory from June 2014 to March 2016. Patient demographics, tumor characteristics, treatment, and HIV status were collected. We describe epidemiology of the cancer caseload, registry design, and costs associated with registry operations. Results Among 1,446 registered patients, Kaposi sarcoma and cervical cancer were the most common cancers among men and women, respectively. Burkitt lymphoma was most common cancer among children. The current rate of pathology confirmation is 65%, a vast improvement in the diagnostic capacity for cancer through the hospital's pathology laboratory. Among leading cancer types, an alarming proportion occurred at young ages; 50% of Kaposi sarcoma and 25% of esophageal, breast, and cervical cancers were diagnosed among those younger than 40 years of age. A systematic, cross-sectional assessment of HIV status reveals a prevalence of 58% among adults and 18% among children. Conclusion We report a high caseload among typically young patients and a significant burden of HIV infection among patients with cancer. In low- and middle-income countries with intermittent, sparse, or nonexistent cancer surveillance, hospital-based cancer registries can provide important local epidemiologic data while efforts to expand population-based registration continue.
Assuntos
Infecções por HIV/epidemiologia , HIV/patogenicidade , Feminino , Hospitais de Ensino , Humanos , Malaui , Masculino , Pessoa de Meia-IdadeRESUMO
Across much of Africa, there is a critical shortage of pathology services necessary for clinical care. Even in settings where specialty-level clinical care, such as medical oncology, is available, access to anatomic pathology services has often lagged behind. Pathology laboratories in the region are challenging to establish and maintain. This article describes the successful implementation of telepathology services in Malawi and reviews other successful programs developed to support diagnostic pathology in resource-limited settings.
Assuntos
Patologia Clínica , Telepatologia , África , Diagnóstico por Imagem , Humanos , InternetRESUMO
Plasmablastic lymphoma (PBL) clinical descriptions are scarce from sub-Saharan Africa (SSA) where both HIV and EBV are highly endemic. We identified 12 patients with pathologically confirmed PBL from a prospective cohort in Lilongwe, Malawi. Median age was 46 (range 26-71), seven (58%) were male, and six (50%) were HIV-positive. Eight patients were treated with CHOP and four with a modified EPOCH regimen. One-year overall survival was 56% (95% CI 24-79%), without clear differences based on HIV status. PBL occurs in Malawi in HIV-positive and HIV-negative individuals and can be treated successfully with curative intent, even in a low-resource setting in SSA.