Clonality studies in myelodysplasia and acute myeloid leukemia

In adult humans, the production of blood cells or hematopoiesis is mainly restricted to the bone marrow. A small number of pluripotent stem cells, which are capable of selfrenewal, can generate committed progenitor cells. The latter are ineversibly committed to the granulocytic, monocytic, erythroid, megakaryocytic or the lymphoid cell lineage. After proliferation and differentiation, the mature blood cells entcr the circulation. The granulocytic and monocytic cells may be designated as myeloid cells; the erythroid cells are sometimes also included in this group. The blood cell formation is regulated by hematopoietic growth factors and cellular interactions e.g. with bone marrow stromal cells. Malignant transformation of hematopoietic cells results in ineffective hematopoiesis. Progenitor and/or precursor cells may accumulate due to a maturation arrest. Depending on the cell lineage involved, these disorders are refelTed to as myeIodysplastic syndrome, acute myeloid or lymphoblastic leukemia, myeloproliferative or lymphoproIiferative disease. The myelodyspIastic syndrome and acute myeloid leukemia are the subjects of investigation of this thesis

Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called "remainder of the body" to the bone marrow