Bone marrow transplantation has become an accepted form of therapy for malignant disorders and potentially lethal hematologic disorders. Although hematologic reconstitution in transplanted patients occurs between ten and 21 days after bone marrow transplantation, platelet recovery is the last to occur. Some patients never again attain a normal platelet count. These patients may have a worse prognosis. Little is known concerning the mechanism of delayed platelet recovery after bone marrow transplantation. The delayed platelet recovery may be due to inadequate transfusion of megakaryocyte progenitors, failure of these progenitors to seed the recipient's bone marrow, failure of a hormonal response to sustain megakaryocytopoiesis or an inhibitor to megakaryocytopoiesis. With the aid of in vitro culture cloning techniques for hematopoietic progenitor cells in semisolid media, platelet-megakaryocyte reconstitution in patients undergoing bone marrow transplantation will be studied including the humoral response associated with decreased platelet count. Specifically, the following will be studied: 1) the number of megakaryocyte progenitors in the donor bone marrow, 2) the number of megakaryocyte progenitors in recipients during engraftment and recovery from bone marrow transplantation, 3) the level of megakaryocyte-stimulating activity in the sera of post bone marrow transplantation patients (The adequacy of the increased activity will be assessed in relation to the number of megakaryocytes in their bone marrow.), 4) the presence of serum inhibitors of megakaryocytopoiesis and 5) the megakaryocyte stimulating activity present in the serum of these patients, isolated by classic protein fractionation techniques. The completion of this study will provide a better understanding of bone marrow reconstitution and platelet recovery. It will document the relationships between megakaryocyte stimulating activity and the presence of megakaryocytes in the bone marrow. It also will provide reasonably pure preparations of the controlling hormone for future studies. Lastly, the better understanding of megakaryocytopoiesis should allow bone marrow transplant clinicians to develop better bone marrow transplantation regimens in the future.
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