Retrospective analysis of pediatric patients with Burkitt lymphoma treated in Tanzania following the implementation of the 2016 National Treatment Guidelines: Poor outcomes to current standard-of-care therapy.

BACKGROUND: Despite the excellent outcomes achieved in the treatment of pediatric Burkitt lymphoma (BL) in high-income countries (HICs), outcomes remain poor in low- and middle-income countries (LMICs). Efforts to improve BL outcomes in Tanzania included the creation of National Treatment Guidelines in 2016. However, disease outcomes in Tanzania following the creation of these guidelines have not been reported to date. PROCEDURE: Historical records from 2016 to 2021 for patients 0-18 years of age with a diagnosis of BL and seen at Bugando Medical Centre (BMC), in Mwanza, Tanzania, were curated into an electronic database and analyzed descriptively. Patients in this cohort were treated per the Tanzanian National Treatment Guidelines, which include six cycles of cyclophosphamide, vincristine, and methotrexate (COM) chemotherapy with intrathecal methotrexate and cytarabine. RESULTS: In total, 92 BL patients' records were eligible for analysis. Patients in this cohort were most commonly Murphy stage II (28%) or stage III (34%). Nearly all, 91%, met International Network for Cancer Treatment and Research (INCTR) high-risk criteria at presentation. Forty-two percent of patients did not receive a biopsy and were treated with a presumed diagnosis of BL alone. A 1-year event-free survival of 29.6% (95% confidence interval [CI]: 20.3%-39.5%) and a 1-year overall survival of 38.5% (95% CI: 28%-48.9%) were observed. A high rate of treatment abandonment (34%) was also observed. CONCLUSION: In a historical cohort of pediatric patients with BL treated per the 2016 Tanzanian National Treatment Guidelines, we observed poor outcomes and a high rate of abandonment. These outcomes appear inferior to those achieved in the INCTR clinical trial that informed the guidelines' creation, and highlights the importance of "real-world" outcomes data in LMICs. These data reinforce the idea that continued clinical research and capacity building efforts are necessary to improve BL outcomes in LMICs.

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

BACKGROUND: Patient-reportedoutcomes (PROs) that assess health-related quality of life (HRQoL) are increasingly important components of cancer care and research that are infrequently used in sub-Saharan Africa (SSA). METHODS: We administered the Chichewa Pediatric Patient-Reported Outcome Measurement Information System Pediatric (PROMIS)-25 at diagnosis, active treatment, and follow-up among pediatric lymphoma patients in Lilongwe, Malawi. Mean scores were calculated for the six PROMIS-25 HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference). Differences in HRQoL throughout treatment were compared using the minimally important difference (MID) and an ANOVA analysis. Kaplan-Meier survival estimates and Cox hazard ratios for mortality are reported. RESULTS: Seventy-five children completed PROMIS-25 surveys at diagnosis, 35 (47%) during active treatment, and 24 (32%) at follow-up. The majority of patients died (n = 37, 49%) or were lost to follow-up (n = 6, 8%). Most (n = 51, 68%) were male, median age was 10 (interquartile range [IQR] 8-12), 48/73 (66%) presented with advanced stage III/IV, 61 (81%) were diagnosed with Burkitt lymphoma and 14 (19%) Hodgkin lymphoma. At diagnosis, HRQoL was poor across all domains, except for Peer Relationships. Improvements in HRQoL during active treatment and follow-up exceeded the MID. On exploratory analysis, fair-poor PROMIS Mobility <40 and severe Pain Intensity = 10 at diagnosis were associated with increased mortality risk and worse survival, but were not statistically significant. CONCLUSIONS: Pediatric lymphoma patients in Malawi present with poor HRQoL that improves throughout treatment and survivorship. Baseline PROMIS scores may provide important prognostic information. PROs offer an opportunity to include patient voices and prioritize holistic patient-centered care in low-resource settings.

The crystal structure of pyrimidine/thiamin biosynthesis precursor-like domain-containing protein CAE31940 from proteobacterium Bordetella bronchiseptica RB50, and evolutionary insight into the NMT1/THI5 family.

We report a 2.0 Å structure of the CAE31940 protein, a proteobacterial NMT1/THI5-like domain-containing protein. We also discuss the primary and tertiary structure similarity with its homologs. The highly conserved FGGXMP motif was identified in CAE31940, which corresponds to the GCCCX motif located in the vicinity of the active center characteristic for THi5-like proteins found in yeast. This suggests that the FGGXMP motif may be a unique hallmark of proteobacterial NMT1/THI5-like proteins.