Treatment Outcomes in CML Patients Treated With Tyrosine Kinase Inhibitors at a Tertiary Teaching Hospital in South Africa.

BACKGROUND: Chronic myeloid leukemia (CML) has become one of the most treatable hematologic neoplasms since the advent of the tyrosine kinase inhibitors (TKIs), but it was not known if similar treatment outcomes could be achieved in a resource-limited country. We tested the hypothesis that, despite challenges to access to second-generation TKIs, excellent responses could be replicated in the setting of limited resources. PATIENTS AND METHODS: Records of 58 patients with newly diagnosed CML in the chronic phase treated with TKIs at a tertiary teaching hospital in Cape Town, South Africa between 2003 and 2012 were reviewed and assessed according to European LeukemiaNet (ELN) criteria. RESULTS: After a median follow-up of 60.5 months, progression-free survival at 60 and 96 months was 79.98% and 68.4%, respectively. Overall survival at 60 and 96 months was 92.9% and 83.6%, respectively. Progression to blast phase at 60 months was associated with poorer survival (P = .0002) but progression to accelerated phase was not (P = .1456). Attainment of a complete cytogenetic response at 12 months (P = .28) or major molecular response at 18 months (P = .268) did not have prognostic significance. CONCLUSION: Despite delays in achievement of the target responses defined according to ELN criteria, the use of imatinib mesylate as a first-line treatment can still result in treatment outcomes comparable with those in developed countries. These data suggest opportunities for improvement and success might be even greater with uninterrupted access to second-generation or newer TKIs.

Molecular characterisation of gastrointestinal stromal tumours in a South African population.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.