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This mathematical model delves into the dynamics of the immune system during Chronic Myeloid Leukemia (CML) therapy with imatinib. The focus lies in elucidating the allergic reactions induced by imatinib, specifically its impact on T helper (Th) cells and Treg cells. The model integrates cellular interactions, drug pharmacokinetics, and immune responses to unveil the mechanisms underlying the dominance of Th2 over Th1 and Treg cells, leading to allergic manifestations. Through a system of coupled delay differential equations, the interplay between healthy and leukemic cells, the influence of imatinib on T cell dynamics, and the emergence of allergic reactions during CML therapy are explored.

The advances in the mathematical explanation of the dynamics underlying treated cancer has opened the door to the mathematical design of optimal therapies. In parallel, the improvements and cost reductions in experimentation and data analysis techniques have made the formulation of personalized therapies possible. However, the design of cancer therapies making use of optimal control theory has not fully considered this possibility in detail. In this paper we contribute to the existing literature by analyzing the diverse alternatives that optimal therapy models offer to design personalized treatments. Taking as the starting point the Chronic Myeloid Leukemia (CML) optimal therapy model in [25], we design personalized optimal therapy models for patients with: CML; CML with intrinsic and/or induced resistance to the administered drug; CML and suffering high drug toxicity and/or allergy to the administered drug; and CML with presence of adverse factors. Along the paper we show that the clinical and medical applicability -the ultimate objective of this biomathematical research- of our proposed personalized models relies on the joint and proper use of the implemented calibration, simulation, and mathematical approaches and techniques. All the theoretical results generated by our personalized optimal therapy models are corroborated by clinical evidence.

Background: Gastrointestinal stromal tumour (GIST) is the commonest mesenchymal malignancy of the gastrointestinal tract. Patient demographics and outcomes following imatinib therapy in South Africa are unknown. Aim: To establish the patient demographics of GIST and the clinical outcomes following imatinib therapy. Setting: Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa. Methods: A quantitative, retrospective, descriptive chart review study was conducted. The study population included patients with a histologic diagnosis of GIST who presented between January 2005 and December 2015 to the facility. Only patients who received imatinib were included in the clinical outcome analysis. Results: Sixty-nine patients were seen during the study period. The mean (SD) age at diagnosis was 57.3 (13.5) years. The male gender (53.6%) was predominant, the black ethnic group (53.6%) was the commonest and the stomach (69.6%) was the most common disease site. Localised disease (53.6%) was the commonest disease category, while high risk (29.7%) and intermediate risk (29.7%) were the majority risk categories. Thirty-six (52.2%) patients received imatinib with a median (IQR) follow-up time of 20.5 (38) months. Eighty-one per cent of patients with localised disease remained in remission after adjuvant imatinib, and 18.2% developed metastatic recurrence. Among patients with locally advanced disease, 81.8% attained partial response on neoadjuvant imatinib, while 9.1% had stable disease. Most (75%) patients with metastatic disease attained partial response as the best response to imatinib. The most common adverse effects were anaemia and fluid overload. Conclusion: At IALCH, GIST is more common in the male gender, black ethnic group and in the stomach. The majority of localised and locally advanced GIST patients have favourable outcomes on imatinib. However, most metastatic GIST patients eventually develop resistance to imatinib necessitating further treatment options.

Imatinib mesylate, as treatment for gastrointestinal stromal tumors (GIST), has dramatically changed the prognosis for survival – not only because it is efficacious, but also because it attracted attention to this malignant disease. GIST is now a well-known disease entity and a paradigm for targeted therapies in malignant diseases. A now 74-year-old patient presented with recurrence of a primary duodenal GIST (initial diagnosis and primary resection in 1998; diameter 10 cm, KIT exon 11 mutation, PM V559D) and liver metastasis after a second surgical resection was performed in 2000. Conventional chemotherapy with adriamycin and ifosfamide failed to control growth of the relapsed tumor and liver metastasis. In July 2001, compassionate use of imatinib was started. Tumor regression was observed at continuous follow-ups (every 2 months for the first 6 months, and 6 months thereafter) and persisted until now. The patient’s physical performance has remained in good condition. Side effects consisted of periorbital edema and sudden muscle cramps of toes and fingers, pain of bones and joints, an intentional tremor, a paler color of the skin, as well as a slight anemia. Imatinib is the first orally administered anticancer drug. Our case shows that a sustained response is possible with continuous therapy over a long time, if the drug is well tolerated. This implies a high compliance of the patient and suggests that resistance to imatinib does not have to develop. Exon 11 (point) mutation might not only represent a positive predictor for imatinib response in general, but especially for imatinib response on long-term.