Application of the linear-quadratic model to myelotoxicity associated with radioimmunotherapy. 1996

R B Wilder, and G L DeNardo, and S Sheri, and J F Fowler, and B W Wessels, and S J DeNardo
Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California 95817, USA.

The purposes of this study were: (1) to use the linear-quadratic model to determine time-dependent biologically effective doses (BEDs) that were delivered to the bone marrow by multiple infusions of radiolabeled antibodies, and (2) to determine whether granulocyte and platelet counts correlate better with BED than administered radioactivity, which does not take stem cell repopulation, i.e., time, into consideration. Twenty patients with B-cell malignancies that had progressed despite intensive chemotherapy and who had a significant number of malignant cells in their bone marrow were treated with multiple 0.7-3.7 GBq/m2 (18-100 mCi/m2) intravenous infusions of Lym-1, a murine monoclonal antibody that binds to a tumour-associated antigen, labeled with iodine-131. Granulocyte and platelet counts were measured in order to assess bone marrow toxicity. BEDs were calculated according to the formula: BED=D(1+gD/(alpha/beta))-0.693(Tn-Tk)/alphaTp, where D represents the absorbed dose of radiation delivered to the red marrow by penetrating emissions of 131I throughout the whole body and nonpenetrating emissions of 131I in the blood and bone marrow, g is a factor that depends on the duration of irradiation relative to the repair half-life of human bone marrow, alpha is the coefficient of nonrepairable damage per Gy, beta is the coefficient of repairable damage per Gy2, Tn is the time required to reach the granulocyte or platelet count nadir after an 131I-Lym-1 infusion, Tk is the time at which bone marrow proliferation begins after the start of treatment and Tp is the doubling time of the bone marrow after the granulocyte or platelet count nadir has been reached. The cumulative 131I-Lym-1 radioactivity administered to each patient was calculated. Biologically effective doses from multiple 131I-Lym-1 infusions were summated in order to arrive at a total BED for each patient. There was a weak association between granulocyte and platelet counts and radioactivity (the correlation coefficients were -0.23 and -0.60, respectively). Likewise, there was a weak association between granulocyte and platelet counts and BED (the correlation coefficients were -0.27 and -0.40, respectively). The attempt to take bone marrow absorbed doses and overall treatment time into consideration with the linear-quadratic model did not produce a stronger association than was observed between peripheral blood counts and administered radioactivity. The association between granulocyte and platelet counts and BED may have been weakened by several factors, including variable bone marrow reserve at the start of 131I-Lym-1 therapy and the delivery of heterogeneous absorbed doses of radiation to the bone marrow.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008228 Lymphoma, Non-Hodgkin Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease. Non-Hodgkin Lymphoma,Diffuse Mixed Small and Large Cell Lymphoma,Diffuse Mixed-Cell Lymphoma,Diffuse Small Cleaved-Cell Lymphoma,Diffuse Undifferentiated Lymphoma,Lymphatic Sarcoma,Lymphoma, Atypical Diffuse Small Lymphoid,Lymphoma, Diffuse,Lymphoma, Diffuse, Mixed Lymphocytic-Histiocytic,Lymphoma, High-Grade,Lymphoma, Intermediate-Grade,Lymphoma, Low-Grade,Lymphoma, Mixed,Lymphoma, Mixed Cell, Diffuse,Lymphoma, Mixed Lymphocytic-Histiocytic,Lymphoma, Mixed Small and Large Cell, Diffuse,Lymphoma, Mixed-Cell,Lymphoma, Mixed-Cell, Diffuse,Lymphoma, Non-Hodgkin's,Lymphoma, Non-Hodgkin, Familial,Lymphoma, Non-Hodgkins,Lymphoma, Nonhodgkin's,Lymphoma, Nonhodgkins,Lymphoma, Pleomorphic,Lymphoma, Small Cleaved Cell, Diffuse,Lymphoma, Small Cleaved-Cell, Diffuse,Lymphoma, Small Non-Cleaved-Cell,Lymphoma, Small Noncleaved-Cell,Lymphoma, Small and Large Cleaved-Cell, Diffuse,Lymphoma, Undifferentiated,Lymphoma, Undifferentiated, Diffuse,Lymphosarcoma,Mixed Small and Large Cell Lymphoma, Diffuse,Mixed-Cell Lymphoma,Mixed-Cell Lymphoma, Diffuse,Non-Hodgkin's Lymphoma,Reticulosarcoma,Reticulum Cell Sarcoma,Reticulum-Cell Sarcoma,Sarcoma, Lymphatic,Sarcoma, Reticulum-Cell,Small Cleaved-Cell Lymphoma, Diffuse,Small Non-Cleaved-Cell Lymphoma,Small Noncleaved-Cell Lymphoma,Undifferentiated Lymphoma,Diffuse Lymphoma,Diffuse Lymphomas,Diffuse Mixed Cell Lymphoma,Diffuse Mixed-Cell Lymphomas,Diffuse Small Cleaved Cell Lymphoma,Diffuse Undifferentiated Lymphomas,High-Grade Lymphoma,High-Grade Lymphomas,Intermediate-Grade Lymphoma,Intermediate-Grade Lymphomas,Low-Grade Lymphoma,Low-Grade Lymphomas,Lymphatic Sarcomas,Lymphocytic-Histiocytic Lymphoma, Mixed,Lymphocytic-Histiocytic Lymphomas, Mixed,Lymphoma, Diffuse Mixed-Cell,Lymphoma, Diffuse Undifferentiated,Lymphoma, High Grade,Lymphoma, Intermediate Grade,Lymphoma, Low Grade,Lymphoma, Mixed Cell,Lymphoma, Mixed Lymphocytic Histiocytic,Lymphoma, Non Hodgkin,Lymphoma, Non Hodgkin's,Lymphoma, Non Hodgkins,Lymphoma, Nonhodgkin,Lymphoma, Small Non Cleaved Cell,Lymphoma, Small Noncleaved Cell,Lymphosarcomas,Mixed Cell Lymphoma,Mixed Cell Lymphoma, Diffuse,Mixed Lymphocytic-Histiocytic Lymphoma,Mixed Lymphocytic-Histiocytic Lymphomas,Mixed Lymphoma,Mixed Lymphomas,Mixed-Cell Lymphomas,Non Hodgkin Lymphoma,Non Hodgkin's Lymphoma,Non-Cleaved-Cell Lymphoma, Small,Non-Hodgkins Lymphoma,Noncleaved-Cell Lymphoma, Small,Nonhodgkin's Lymphoma,Nonhodgkins Lymphoma,Pleomorphic Lymphoma,Pleomorphic Lymphomas,Reticulosarcomas,Reticulum Cell Sarcomas,Reticulum-Cell Sarcomas,Sarcoma, Reticulum Cell,Small Cleaved Cell Lymphoma, Diffuse,Small Non Cleaved Cell Lymphoma,Small Non-Cleaved-Cell Lymphomas,Small Noncleaved Cell Lymphoma,Small Noncleaved-Cell Lymphomas,Undifferentiated Lymphoma, Diffuse,Undifferentiated Lymphomas
D010976 Platelet Count The number of PLATELETS per unit volume in a sample of venous BLOOD. Blood Platelet Count,Blood Platelet Number,Platelet Number,Blood Platelet Counts,Blood Platelet Numbers,Count, Blood Platelet,Count, Platelet,Counts, Blood Platelet,Counts, Platelet,Number, Blood Platelet,Number, Platelet,Numbers, Blood Platelet,Numbers, Platelet,Platelet Count, Blood,Platelet Counts,Platelet Counts, Blood,Platelet Number, Blood,Platelet Numbers,Platelet Numbers, Blood
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D006098 Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS. Granulocyte
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000380 Agranulocytosis A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS). Granulocytopenia,Agranulocytoses,Granulocytopenias
D013921 Thrombocytopenia A subnormal level of BLOOD PLATELETS. Thrombopenia,Thrombocytopenias,Thrombopenias

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