Feasibility of upfront mobile money transfers for transportation reimbursement to promote retention among patients receiving lymphoma treatment in Malawi.

BACKGROUND: Cancer outcomes in sub-Saharan Africa (SSA) remain suboptimal, in part due to poor patient retention. Many patients travel long distances to receive care, and transportation costs are often prohibitively expensive. These are well-known and established causes of delayed treatment and care abandonment in Malawi and across SSA. METHODS: We sent visit reminder texts and offered upfront money to cover transportation costs through a mobile money transfer (MMT) platform to lymphoma patients enrolled in a prospective cohort in Malawi. The primary aim was to test the feasibility of upfront MMTs. RESULTS: We sent 1034 visit reminder texts to 189 participating patients. Of these texts, 614 (59%) were successfully delivered, with 536 (52%) responses. 320/536 (60%) MMTs were sent to interested patients and 312/320 (98%) came to their appointment on time. Of 189 total patients, 120 (63%) were reached via text and 84 (44%) received MMTs a median of three times (IQR 2-5). Median age of reachable patients was 41 (IQR 30-50), 75 (63%) were male, 62 (52%) were HIV+ and 79 (66%) resided outside of Lilongwe. CONCLUSION: MMTs were a feasible way to cover upfront transportation costs for patients reachable via text, however many of our patients were unreachable. Future studies exploring barriers to care, particularly among unreachable patients, may help improve the efficacy of MMT initiatives and guide retention strategies throughout SSA.

Risk factors and reasons for treatment abandonment among children with lymphoma in Malawi.

PURPOSE: Lymphoma is the commonest pediatric cancer in sub-Saharan Africa (SSA). Frequent treatment abandonment contributes to suboptimal outcomes. We examined risk factors and reasons for treatment abandonment for this population in Malawi. METHODS: We conducted a mixed methods study among children < 18 years old with newly diagnosed lymphoma, prospectively enrolled during 2013-2016. All children received standardized diagnosis and treatment, and were followed for up to 2 years. Treatment abandonment was defined as failure to attend prescribed chemotherapy within 4 weeks, or post-treatment visit within 3 months. Child, guardian, and household characteristics associated with treatment abandonment were assessed. Semi-structured interviews were conducted with primary caregivers of children experiencing treatment abandonment. RESULTS: Of 121 children with newly diagnosed lymphoma, 72 (60%) had complete information regarding child, guardian, and household characteristics. Of these, 56 (78%) had Burkitt's and 16 (22%) Hodgkin's lymphoma. Forty-nine (68%) were male, median age was 10.6 years (interquartile range [IQR] 7.9-13.0), and 26 (36%) experienced treatment abandonment. Lack of guardian education and travel time ≥ 4 h to clinic were independently associated with treatment abandonment, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5-8.9, p = 0.005] and aHR 2.9 (95% CI 1.2-6.9, p = 0.019), respectively. Commonest reasons for treatment abandonment endorsed by 15 guardians were community influence, suboptimal clinic environment, logistical challenges, transport costs, treatment toxicities, loss of hope, alternative healers, and beliefs about cure. CONCLUSIONS: These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA.

Identifying opportunities to bridge disparity gaps in curing childhood cancer in Malawi: Malignancies with excellent curative potential account for the majority of diagnoses.

The majority of African children with cancer die without access to resources. We describe efforts to build a public treatment program with curative intent for childhood cancer in Lilongwe, Malawi despite severe limitations in diagnostic and therapeutic resources. We retrospectively analyzed a cohort of childhood cancer patients at Kamuzu Central Hospital from 12/2011-6/2013. Consistently available chemotherapeutic agents were limited to cyclophosphamide, vincristine, doxorubicin, bleomycin, methotrexate, and prednisone. Of 258 newly diagnosed childhood malignancies, 17 patients with retinoblastoma were excluded from clinical analyses due to insufficient clinical data. Among the remainder of the cohort (n = 241), 42% were female with median age 8.4 years (range 0.6-17.9). Forty-six (19%) were HIV-infected (42 Kaposi sarcoma, 3 Burkitt lymphoma, 1 Hodgkin lymphoma). The most common clinical presentations were palpable abdominal mass (41%), peripheral lymphadenopathy (33%), and jaw mass (17%). Nearly two-thirds of total diagnoses were accounted for by Burkitt lymphoma (n = 74), Kaposi sarcoma (n = 52), Hodgkin lymphoma (n = 21), and Wilms tumor (n = 19). Twelve-month overall survival for these 4 most common diagnoses was 54% (95% confidence interval 46-61) versus 19% (95% confidence interval 11-30) for all other diagnoses (median follow-up 19 months). Treatment-related mortality was highest in patients with non-Wilms solid tumors of the abdomen (48% versus 10% for the overall cohort, p < 0.001), while treatment abandonment was highest in patients with bone and soft-tissue sarcomas (29% versus 14% overall, p = 0.05). Childhood cancers with excellent curative potential accounted for the majority of patients, establishing an opportunity to build treatment programs with curative intent despite severe limitations.

Beyond Endemic Burkitt Lymphoma: Navigating Challenges of Differentiating Childhood Lymphoma Diagnoses Amid Limitations in Pathology Resources in Lilongwe, Malawi.

Background. Although Burkitt lymphoma (BL) is the most common childhood lymphoma in sub-Saharan Africa, Hodgkin lymphoma (HL) and other non-Hodgkin lymphomas occur. Diagnosing non-jaw mass presentations is challenging with limited pathology resources. Procedure. We retrospectively analyzed 114 pediatric lymphomas in Lilongwe, Malawi, from December 2011 to June 2013 and compared clinical versus pathology-based diagnoses over two time periods. Access to pathology resources became more consistent in 2013 compared with 2011-2012; pathology interpretations were based on morphology only. Results. Median age was 8.4 years (2.1-16.3). The most common anatomical sites of presentation were palpable abdominal mass 51%, peripheral lymphadenopathy 35%, and jaw mass 34%. There were 51% jaw masses among clinical diagnoses versus 11% in the pathology-based group (P < .01), whereas 62% of pathology diagnoses involved peripheral lymphadenopathy versus 16% in the clinical group (P < .01). The breakdown of clinical diagnoses included BL 85%, lymphoblastic lymphoma (LBL) 9%, HL 4%, and diffuse large B-cell lymphoma (DLBCL) 1%, whereas pathology-based diagnoses included HL 38%, BL 36%, LBL 15%, and DLBCL 11% (P < .01). Lymphoma diagnosis was pathology confirmed in 19/66 patients (29%) in 2011-2012 and 28/48 (60%) in 2013 (P < .01). The percentage of non-BL diagnoses was consistent across time periods (35%); however, 14/23 (61%) non-BL diagnoses were pathology confirmed in 2011-2012 versus 16/17 (94%) in 2013. Conclusions. Lymphomas other than Burkitt accounted for 35% of childhood lymphoma diagnoses. Over-reliance on clinical diagnosis for BL was a limitation, but confidence in non-BL diagnoses improved with time as pathology confirmation became standard. Increased awareness of non-BL lymphomas in equatorial Africa is warranted.

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 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.

Quantifying bias in survival estimates resulting from loss to follow-up among children with lymphoma in Malawi.

Pediatric lymphoma is common in sub-Saharan Africa, where survival estimates are often based on limited follow-up with incomplete retention, introducing potential for bias. We compared follow-up and overall survival (OS) between passive and active tracing within a prospective cohort of children with lymphoma in Malawi. Median follow-up times were 4.4 months (interquartile range [IQR] 2.0-9.4) and 10.8 months (IQR 6.2-20.6) in passive and active follow-up, respectively. Twelve-month overall survival (OS) was 69% (95% confidence interval [CI] 54-80) in passive and 44% (95% CI 34-54) in active follow-up. Passive follow-up significantly overestimated the OS and underestimated the mortality. Efforts to improve retention in regional studies are needed.

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

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.

Accurate Real-Time Diagnosis of Lymphoproliferative Disorders in Malawi Through Clinicopathologic Teleconferences: A Model for Pathology Services in Sub-Saharan Africa.

OBJECTIVES: The incidence of lymphoproliferative disorders (LPDs) is increasing in sub-Saharan Africa (SSA) due to population growth, aging, and human immunodeficiency virus (HIV). Despite significant burden, resources for diagnosis and treatment of LPDs are limited, with little infrastructure to deliver modern pathology services. Diagnostic and therapeutic decisions are therefore frequently made without tissue confirmation, leading to high rates of misdiagnosis and inappropriate treatment. METHODS: We have established a laboratory in Malawi to support clinical and research efforts at a national teaching hospital. Consensus real-time diagnoses are rendered by local pathologists after weekly clinicopathologic teleconferences involving clinicians and pathologists from the United States and Malawi. Additional ancillary studies are then performed in the United States prior to final diagnosis. RESULTS: We report our first 2 years' experience and demonstrate high concordance between real-time diagnoses in Malawi and final diagnoses in the United States (5% major discordance rate for formalin-fixed, paraffin-embedded samples). In addition, we describe characteristics of pathologically confirmed LPDs in Malawi, highlighting differences by HIV status. CONCLUSIONS: Our multidisciplinary approach can be a model for strong pathology services that provide direct, real-time support to clinical care and research in SSA.

Recruiting the social contacts of patients with STI for HIV screening in Lilongwe, Malawi: process evaluation and assessment of acceptability.

OBJECTIVES: To explore acceptability of recruiting social contacts for HIV and sexually transmitted infection (STI) screening in Lilongwe, Malawi. METHODS: In this observational study, three groups of 'seed' patients were enrolled: 45 HIV-infected patients with STI, 45 HIV-uninfected patients with STI and 45 community controls, who were also tested for HIV as part of the study. Each seed was given five coupons and asked to recruit up to five social contacts to the STI clinic. Seeds were told the programme for contacts would include HIV testing, STI screening and general health promotion. Seeds were asked to return after 1 month to report on the contact recruitment process. Seeds received $2 for each successfully recruited contact. RESULTS: Eighty-nine seeds (66%) returned for 1-month follow-up with no difference between the three seed groups (p=0.9). Returning seeds reported distributing most of their coupons (mean=4.1) and discussing each feature of the programme with most contacts-HIV testing (90%), STI screening (87%) and health promotion (91%). Seeds reported discussing their own HIV status with most contacts (52%), with a lower proportion of HIV-infected seeds discussing their HIV status (22%) than HIV-uninfected seeds (81%) or community seeds (64%) (p<0.001). Contact recruitment did not vary with socioeconomic status. CONCLUSIONS: Most seeds distributed all coupons and reported describing all aspects of the programme to most contacts. Patients with STI are able to act as health promoters within their social networks and may be a critical link to increasing STI and HIV status awareness among high-risk groups.

Outcomes for paediatric Burkitt lymphoma treated with anthracycline-based therapy in Malawi.

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.