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Chemotherapy Drug Scheduling for the 
Induction Treatment of Patients With 
Acute Myeloid Leukemia 
Leukemia is an immediately life-threatening cancer wherein immature blood cells are 
overproduced, accumulate in the bone marrow (BM) and blood and causes immune and 
blood system failure. Treatment with chemotherapy can be intensive or nonintensive and 
can also be life-threatening since only relatively few patient-specific and leukemia-specific 
factors are considered in current protocols. We have already presented a mathematical 
model for one intensive chemotherapy cycle with intravenous (IV) daunorubicin (DNR), and 
cytarabine (Ara-C) [1]. This model is now extended to nonintensive subcutaneous (SC) Ara- 
C and for a standard intensive chemotherapy course (four cycles), consistent with clinical 
practice. Model parameters mainly consist of physiological patient data, indicators of tumor 
burden and characteristics of cell cycle kinetics. A sensitivity analysis problem is solved and 
cell cycle parameters are identified to control treatment outcome. Simulation results using 
published cell cycle data from two acute myeloid leukemia patients [2] are presented for a 
course of standard treatment using intensive and nonintensive protocols. The aim of 
remission–induction therapy is to debulk the tumor and achieve normal BM function; by 
treatment completion, the total leukemic population should be reduced to at most 
10$^{9}$ cells, at which point BM hypoplasia is achieved. The normal cell number should be 
higher than that of the leukemic, and a 3-log reduction is the maximum permissible level of 
population reduction. This optimization problem is formulated and solved for the two patient 
case studies. The results clearly present the benefits from the use of optimization as an 
advisory tool for treatment design.

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Chemotherapy drug scheduling for the induction treatment of patients with acute myeloid leukemia

  • 1. Chemotherapy Drug Scheduling for the Induction Treatment of Patients With Acute Myeloid Leukemia Leukemia is an immediately life-threatening cancer wherein immature blood cells are overproduced, accumulate in the bone marrow (BM) and blood and causes immune and blood system failure. Treatment with chemotherapy can be intensive or nonintensive and can also be life-threatening since only relatively few patient-specific and leukemia-specific factors are considered in current protocols. We have already presented a mathematical model for one intensive chemotherapy cycle with intravenous (IV) daunorubicin (DNR), and cytarabine (Ara-C) [1]. This model is now extended to nonintensive subcutaneous (SC) Ara- C and for a standard intensive chemotherapy course (four cycles), consistent with clinical practice. Model parameters mainly consist of physiological patient data, indicators of tumor burden and characteristics of cell cycle kinetics. A sensitivity analysis problem is solved and cell cycle parameters are identified to control treatment outcome. Simulation results using published cell cycle data from two acute myeloid leukemia patients [2] are presented for a course of standard treatment using intensive and nonintensive protocols. The aim of remission–induction therapy is to debulk the tumor and achieve normal BM function; by treatment completion, the total leukemic population should be reduced to at most 10$^{9}$ cells, at which point BM hypoplasia is achieved. The normal cell number should be higher than that of the leukemic, and a 3-log reduction is the maximum permissible level of population reduction. This optimization problem is formulated and solved for the two patient case studies. The results clearly present the benefits from the use of optimization as an advisory tool for treatment design.