Medical Research Interview: Dr. Daniel Thomas MD PhD FRACP FRCPA Program Leader, Blood Cancer Precision Medicine Theme at the South Australia Health Medical Research Institute Clinical Hematologist, Royal Adelaide Hospital Associate Professor, Adelaide Medical School, The University of Adelaide MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of CMML? Response: Chronic myelomonocytic leukemia (CMML) is a rare, but increasingly frequent, clonal stem cell disorder that results in hyperproliferation of inflammatory monocytes, a form of white blood cells. It features both myelodysplasia and myeloproliferation. CMML is most often found in older adults and leads to anemia, decreased quality of life, and an increased risk of acute myeloid leukemia (AML). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates production, growth, differentiation, activation, and function of myeloid cells (monocytes, neutrophils, and eosinophils). In the presence of RAS-pathway mutations, a greater sensitivity to GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML).  In CMML, greater sensitivity to GM-CSF stimulates excessive monocytic precursor proliferation. The PREACH-M Trial, which stands for PREcision Approach to CHronic Myelomonocytic Leukemia, assesses the efficacy of lenzilumab in addition to azacitidine in treatment-naïve CMML participants with RAS-pathway mutations (KRAS, NRAS, CBL) and separately high dose ascorbate in participants with TET2 mutations who do not have RAS-pathway mutations. The study is currently underway and actively enrolling.  It is being conducted and funded by the South Australian Health and Medical Research Institute (SAHMRI).  (more…)