Introduction: South Africa has the highest global burden of human immunodeficiency virus (HIV). The HIV seropositive population is at increased risk of developing non-Hodgkin lymphoma, particularly high grade aggressive subtypes such as Burkitt- and Burkittlike lymphoma (also known as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma). Methods: Ten year retrospective review of clinico-pathological features and survival of adults with newly diagnosed Burkitt- and Burkitt-like lymphoma at a tertiary hospital in South Africa. Results: Burkitt lymphoma (BL) (n=109) was more frequent than Burkitt-like lymphoma (BLL) (n=41) and at presentation there were no significant differences in HIV prevalence (86% vs 78%); median CD4 count (213 vs 207 cells/μL); bone marrow involvement (49% vs 34%), leukaemic dissemination (37% vs 27%) and most frequent site of diagnosis (abdomen/pelvis; 26% vs 29%), respectively. There were significant differences in median age (34 vs 41 years, p=0.0319), median lactate dehydrogenase levels (2052 vs 869 U/l, p=0.0011) and cerebrospinal fluid involvement (12% vs 0%, p=0.046). 43% of patients with an available HIV viral load result showed virological supression defined as lower than detectable limit (LDL) with the median value also being LDL. The patients that received high dose chemotherapy including high dose methotrexate (112/150; 75%) showed a one-year survival of 62% with no significant difference between Burkitt and Burkitt-like lymphoma (66 months versus 51 months, respectively; p=0.267). Patients with leukaemic presentation showed a significantly lower mean survival of 24 months compared to those without (72 months; p< 0.001). The 2 year survival for the whole group, regardless of type of treatment received, was 40% (95% CI, 32-48%) with a median survival of 7.5 months. Conclusion: This is the largest cohort of Burkitt- and Burkitt-like lymphoma patients described in South Africa. There was a high HIV prevalence. The majority received intensive chemotherapy and survival was comparable to certain well-resourced countries. Leukaemic presentation was frequent and associated with less favourable survival.

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CML is a haematological malignancy that is characterized by the BCR-ABL fusion oncogene that encodes a constitutively active tyrosine kinase. The treatment of choice for CML is a tyrosine kinase inhibitor and molecular monitoring of patients forms an integral part of disease management. When the expected response to tyrosine kinase inhibitor is not achieved within internationally accepted time frames, acquired resistance to tyrosine kinase inhibitors is suspected. Acquired resistance to tyrosine kinase inhibitors is primarily due to mutations in the BCR-ABL kinase domain. Types of mutations include single base mutations, insertions, deletions as well as duplications. Characterization of these mutations is important for treatment, since the type and position of the mutation may have an effect on how the patient responds to treatment. Although several methods have been described for detecting mutations, DNA sequencing is mostly used. Sequencing is currently the only technique that can simultaneously detect single base mutations, insertions and deletions in the BCR-ABL kinase domain. However, sequencing is costly as some patient samples do not have mutations and the lack of response to treatment is due to non-compliance. Thus, a screening method to exclude samples without mutations would make mutational analysis more cost-effective. High resolution melting (HRM) is a relatively new technique that is being used to screen for mutations, prior to sequencing. HRM has recently been used to screen the region of BCR-ABL encoding for the kinase domain for single base mutations. However, it was unknown whether HRM could be used to identify insertions, deletions or duplications in the kinase domain. This study has shown that HRM can be used to screen for mutations including insertions, deletions and duplications the region of BCR-ABL encoding for the kinase domain, prior to sequencing. HRM was performed on 40 patient samples, 10 of which had confirmed mutations in BCR-ABL in the region of the kinase domain. Of the 10 samples with mutations, three had single base mutations, one with a previously described insertion, seven had novel deletion variants. Furthermore, HRM detected a tandem duplication of the kinase domain in two patient samples that was not previously been possible with sequencing. There was 100% congruency between the detection of mutations using HRM and sequencing results, indicating similar sensitivity. HRM proved successful to indicate the presence of deletion variants. However, the deletion variants were detected in the HRM region preceding the area affected by the deletion. It was confirmed that the detection of the deletion variants was due to the PCR extension of HRM 1 amplicon into the HRM area of the deletion. It has been suggested that the insertion, deletions and duplications detected in this study may result in acquired resistance to tyrosine kinase inhibitor. In conclusion, this was the first study to use high-resolution melting to detect insertions, deletions and duplications in the region of BCR-ABL encoding for the kinase domain, indicating the suitability of the assay for screening for mutations prior to sequencing.