The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We performed a pharmacokinetically (PK) guided dose-escalation feasibility study of vincristine in Kenyan children (NCT05844670). Vincristine PK exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia or malnutrition. None of the fifteen participants developed VIPN. Low vincristine exposure was seen in only one participant: a dose increase was implemented without side-effects. Average vincristine exposure was high. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

Background: In our earlier published outcomes of children with acute lymphoblastic leukemia (ALL) at Moi Teaching and Referral Hospital in Kenya (MTRH), we showed low event-free survival (EFS) with high induction mortality and abandonment. Based on this observation, the team focused on strategies to reduce both causes of poor outcomes. Intervention: We dropped doxorubicin from induction therapy as the supply of L-asparaginase became reliable, improved social and financial support for insurance coverage and transportation, promptly initiated empirical antibiotics during episodes of febrile neutropenia, and enhanced the availability of blood products. Objective: Our study compared childhood ALL outcomes before (2010-2016) and after (2017-2020) modification of induction therapy, with improved social and financial support and supportive care. Methods: We reviewed the medical records of 123 children with ALL between 2017 to 2020. Their treatment results were collected and compared to those of 136 children before the (2010-2016) modification of induction therapy, with improved social and financial support. Results: Three-year EFS estimates improved from 18.2% to 40.7%. Relapse or progressive disease decreased from 26% to 16%, and abandonment from 24% to 14%. Deaths and survival through induction did not change significantly between the two periods. Children between 1-9 years and those with white blood cell (WBC) count <50x10 9/L had better EFS. Conclusions: Treatment abandonment and relapse decreased, and EFS increased significantly. However, strategies to improve early diagnosis and supportive care are needed to reduce induction mortality. In addition, enhanced parental education and continuous counseling are required to minimize treatment abandonment further.

Pleuropulmonary blastoma (PPB) is the most common primary lung tumor of childhood and is associated with somatic or germline DICER1 variants. Recurrent PPB, especially with brain metastases, are difficult to treat and survival is poor. Comprehensive genomic analyses of PPB have been limited in number and depth. The cases presented here identified additional oncogenic drivers from tumor sequencing that could be modulating tumor progression and response to therapy outside of known DICER1 mutations highlighting the need for upfront genomic analysis on all patients with PPB.