Thirty-two patients in the blastic phase of Philadelphia chromosome-positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine--prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine--prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.

Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.