Myelogenous Leukemia In Blast Phase Research Articles

Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia

Mitoxantrone is a substituted anthraquinone with considerable activity against human acute leukemia. The authors' goal was to treat patients with continuous infusion mitoxantrone in order to maintain cytotoxic steady state levels with acceptable toxicity and to assess the results. Daily mitoxantrone levels showed a mean steady state plasma level of 16.8 +/- 1.4 ng/ml (range, 9.1-25.1) with a systemic clearance of 519 +/- 47 ml/minute/m2. No drug accumulation occurred. Mitoxantrone was undetectable 24 hours postinfusion. All patients, including two patients with chronic myelogenous leukemia in blast phase, had greater than 90% reduction in leukemia cell mass (marrow cellularity X percent leukemia cells) by day 6. However, six patients received 3 days of etoposide at that point because of residual acute nonlymphocytic leukemia (ANLL). Overall four patients (36%) had a complete remission; one additional patient had a bone marrow remission but also had a persistent granulocytic sarcoma. Toxicities included severe but tolerable myelosuppression, mucositis, and hepatic dysfunction. There was no correlation between mitoxantrone levels, toxicity, or clinical response. Continuous infusion produces cytotoxic plasma mitoxantrone levels and rapid clearing of ANLL from bone marrow. Further dose escalation may be possible.

Enrichment of cell populations containing terminal deoxynucleotidyl transferase activity by free flow electrophoresis.

Terminal deoxynucleotidyl transferase (TdT) is an enzyme that has been utilized as a biochemical marker for following certain leukemia patients during treatment and remission. The potential usefulness of this enzyme in predicting the onset of relapse before any morphological indications has been demonstrated in chronic myelogenous leukemia patients in blast phase of the disease. In order to be able to detect low levels of TdT activity, especially during remission phase, we have used the technique of free flow electrophoresis to enrich cell populations containing TdT. With this technique we have achieved up to 20-fold enrichment of TdT-positive cell populations from normal human bone marrow, cells from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia in blast phase of the disease. TdT positive cells were not detected in patients with acute myelogenous leukemia and B cell lines. This technique should prove to be useful in early detection of relapse in patients in remission and for enrichment of cell populations containing other biochemical markers.

Enrichment of terminal deoxynucleotidyl transferase activity by cell separation.

Terminal deoxynucleotidyl transferase is a unique DNA polymerase that can carry out DNA synthesis on an initiator molecule in the absence of a template. The usefulness of this enzyme as a biological marker for following patients during treatment and remission has been suggested. The potential usefulness of this enzyme in predicting the onset of relapse before any morphological indications has been demonstrated in chronic myelogenous leukemia patients in blast phase of the disease. In order to be able to detect low levels of TdT activity especially during remission phase, we have used cell separation techniques which can enrich cell populations containing TdT activity. A number of cell separation techniques have been developed to separate different cell types. We have used the techniques of unit gravity sedimentation and free flow electrophoresis to achieve enrichment of TdT positive cell populations. Our results show that up to 20 fold enrichment of TdT activity in normal human bone marrow can be accomplished by using cell separation techniques. With the use of free flow electrophoresis, we have achieved enrichment of TdT positive cell populations from normal human bone marrow, cells from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia in blast phase of the disease. No TdT positive cells were detected in patients with acute myelogenous leukemia. These cell separation techniques should prove to be useful in early detection of relapse in patients in remission.

Antiserum Against Leukemia Cell Ferritin as a Diagnostic Tool for Malignant Neoplasms2

The specific antiserum against a type of ferritin that is especially common to leukemia cells and the placenta was used to test, by countercurrent immunoelectrophoresis, sera from humans with various diseases. The best results were obtained with leukemia; patients with chronic myelogenous leukemia in blastic phase, acute myelogenous leukemia, lymphogenous leukemia, and unclassifiable juvenile leukemia frequently showed a positive reaction, but patients with chronic myelogenous leukemia in static phase did not. The average incidence of positive reaction among all leukemia patients was 54.0%. Patients with other malignant tumors (i.e., multiple myeloma, malignant lymphoma and carcinomas of the stomach, rectum, and liver) also often showed a positive reaction. The average incidence of positive reaction among all the patients with malignant diseases of the hematopoietic system, except for leukemia, was 34.3%, and that among patients with nonhematologic malignant neoplasms was 36.8%. However, the incidence of a positive reaction in patients with benign diseases and healthy individuals was less than 3%.