Tamiwe Tomoka

Hodgkin lymphoma, HIV, and Epstein–Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study

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.

CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.

Plasma Epstein-Barr virus DNA for pediatric Burkitt lymphoma diagnosis, prognosis, and response assessment in Malawi.

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 log10copies/mL for BL, 4.8 log10copies/mL for cHL, and 3.4 log10copies/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 log10copies/mL versus <6 log10copies/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 log10copies/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.

Placental but Not Peripheral Plasmodium falciparum Infection During Pregnancy Is Associated With Increased Risk of Malaria in Infancy

Pregnancy-associated Plasmodium falciparum infection impacts the health of mothers and newborns, but little is known about the effects of these infections on infant susceptibility to malaria. We followed 473 mother-infant pairs during pregnancy and through 2 years of age. We observed that children born to mothers with placental malaria, but not those born to mothers with peripheral infection without evidence of placental sequestration, had increased risk of malaria during the first year of life compared with children born to mothers with no malaria during pregnancy. Malaria infections with placental sequestration have long-lasting impact on infant susceptibility to malaria infection.

Lymphoma and Pathology in Sub-Saharan Africa: Current Approaches and Future Directions

The care of patients with lymphoma relies heavily on accurate tissue diagnosis and classification. In sub-Saharan Africa, where lymphoma burden is increasing because of population growth, aging, and continued epidemic levels of human immunodeficiency virus infection, diagnostic pathology services are limited. This article summarizes lymphoma epidemiology, current diagnostic capacity, and obstacles and opportunities for improving practice in the region.

Practical Successes in Telepathology Experiences in Africa

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.

Targetable subsets of non-Hodgkin lymphoma in Malawi define therapeutic opportunities

Diagnostics and supportive care for patients with non-Hodgkin lymphoma (NHL) in lower- and middle-income countries (LMICs) are lacking. We hypothesized that high-throughput transcription-based diagnostics could classify NHL specimens from Malawi amenable to targeted therapeutics. We established tissue microarrays and classified 328 cases diagnosed by hematoxylin and eosin as NHL at University of Malawi College of Medicine using immunohistochemistry (IHC) for conventional markers and therapeutic targets. A subset was analyzed using NanoString-based expression profiling with parsimonious transcriptional classifiers. Overall, 72% of lymphomas were high-grade B-cell tumors, subsets of which were enriched for expression of MYC, BCL2, and/or PD-L1. A 21-gene transcriptional classifier, previously validated in Western cohorts, divided 96% of diffuse large B-cell lymphomas (DLBCLs) with 100% of B-cell lymphomas, unclassifiable, into 1 cluster and 88% of Burkitt lymphomas into a separate cluster. Cell-of-origin categorization of 36 DLBCLs by NanoString lymphoma subtyping test (LST) revealed 69% concordance with IHC. All discordant cases were classified as germinal center B cell-like (GCB) by LST but non-GCB by IHC. In summary, utilization of advanced diagnostics facilitates objective assessment and segregation of biologically defined subsets of NHL from an LMIC without expert review, thereby establishing a basis for the implementation of effective and less toxic targeted agents.

Frequent HIV and Young Age Among Individuals With Diverse Cancers at a National Teaching Hospital in Malawi

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.

Plasmablastic lymphoma in Malawi

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.

A tailored approach to building specialized surgical oncology capacity: Early experiences and outcomes in Malawi

Objectives Cervical cancer can often be cured by surgery alone, if diagnosed and treated early. However, of the cancer patients who live in the worlds poorest countries less that 5% have access to safe, effective and timely cancer surgery. We designed a novel, competency-based curriculum to rapidly build surgical capacity for the treatment of cervical cancer. Here we report experiences and early outcomes of its implementation in Malawi. Methods Curriculum implementation consisted of preoperative evaluation of patients and surgical video review, discussion of surgical instruments and suture material, deconstruction of the surgical procedure into critical subcomponents including trainees walking through the steps of the procedure with the master trainers, high-volume surgical repetition over a short time interval, intra-operative mentoring, post-operative case review, and mental narration. This was preceded by self-directed learning and followed by clinical mentorship through electronic communication and quarterly on-site visits. Results Between June 2015–June 2017, 28 patients underwent radical abdominal hysterectomy with bilateral pelvic lymphadenectomy. The first 8 surgeries were performed over 5 days. After the 7th case the trainee could perform the procedure alone. During and between quarterly mentoring-visits the trainee independently performed the procedure on 20 additional patients. Major surgical complications were rare. Conclusions Life-saving surgical treatment for cervical cancer is now available for the first time, as a routine clinical service, in Central/Northern, Malawi.