J. H. Tjio

PERSISTENT MITOSIS OF TRANSFUSED HOMOLOGOUS LEUKOCYTES IN CHILDREN RECEIVING ANTILEUKEMIC THERAPY.

Temporary homologous bone marrow grafts were observed in three patients with acute leukemia, receiving intensive antileukemic treatment, following transfusion of peripheral blood cells from donors with chronic myelocytic leukemia. Persistent mitosis of the transfused cells, containing the Philadelphia chromosome marker, were detected by cytogenetic techniques 19, 39, and 52 days after transfusion.

STUDIES OF THE PHILADELPHIA CHROMOSOME IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA

The Philadelphia chromosome (Ph’) is present in myeloid cells in the majority of patients with chronic myelogenous leukemia (CML) and has not been found in other diseases. It has been assumed that the Ph’ chromosome is present only in these cells since it has not been found in cultured skin of patients with CML. This study is concerned with the effects of treatment on the clinical, hematologic, and cytogenetic abnormalities of patients with CML and with the tissue distribution of the Ph’ chromosome. Serial clinical, hematologic, biochemical, and cytogenetic observations were made during 32 drug trials in 24 patients with CML. None of these patients were in the “acute” or “blast” phase of the disease. The treatment employed and the results in terms of clinical and hematological parameters are presented in TABLE 1. Complete remission is defined as: complete abatement of symptoms; disappearance of palpable splenomegaly and lymphadenopathy; return of hemoglobin, platelet count, white-cell count, and differential to normal; and return of the mye1oid:erythroid ratio in the bone marrow to less than 4: 1. For partial remission, the white-cell count must have decreased to the normal range and improvement, not necessarily complete, must have occurred in symptoms and physical findings. Complete remissions occurred in the majority of patients receiving “conventional” therapy, i.e., busulfan, 6-mercatopurine, diacetylmethylcolchicine. The other agents were less effective. Leukocyte alkaline phosphatase (LAP) in the peripheral blood was measured by the biochemical method of Peacock et al. In FIGURE 1 the LAP is plotted with respect to response to therapy. The horizontal stippled bar represents the lower limit of normal. The LAP increased to normal in only 2 of 10 patients who achieved a partial remission, but the majority of patients (1 1 out of 15) who achieved complete clinical and hematologic remissions had normalization of their LAP. The cytogenetic analyses were performed on the bone marrow using the direct, air-dry technique without prior in v i m culture (Tjio and Whang). The results with respect to response to treatment are presented in TABLE 2. Thirty of the 32 patients included in the study were Ph‘ positive. All of the Ph’ positive patients had the Ph’ chromosome present in 90 to 100 per cent of the marrow metaphases. Eight of the 11 patients who achieved a partial remission had chromosome studies, and all 8 were Ph’ positive, the Ph’ chromosome being present in 96-100 per cent of the metaphases scored. This was also true for patients achieving complete remission. Not only was the Ph’ chromosome present in quantity in all patients achieving remission; but in addition, it continued to be present in prolonged (up to six mo.) remissions. A summary of the relative effects of chemotherapy on these various parameters of CML is presented in TABLE 3. Fifteen of 22 patients achieved a complete remission, and 13 of these 15 had normalization of their LAP. Leukocyte acid production and hydrogen ion concentration has been found to be normal in patients with CML by Block rt a/. These improved in 31 per cent of patients treated. However, the Ph’ chromosome persisted in quantity in all patients.

THE EFFECT OF TREATMENT IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA. HEMATOLOGIC AND CYTOGENETIC STUDIES.

Excerpt Chemotherapy or X irradiation produces improvement in the clinical and hematologic abnormalities in the majority of patients with chronic myelogenous leukemia (CML) (1-5). Return of the leu...

Reaction of Human Sera with Mammalian Chromosomes Shown by Fluorescent Antibody Technique

Certain human sera, including sera from five patients with lupus erythematosus, react with mammalian chromosomes. If chromosomal preparations are exposed first to the serum and then to horse antihuman globulin conjugated with fluorescein, the chromosomes will fluoresce. Sera having this activity appear to react with all the chromosomes of the cell.