In the present study, the activity and side effects of high-dose
cytosine arabinoside (HD-
Ara-C) in combination with
mitoxantrone (
mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory
Hodgkin's disease.
Therapy consisted of HD-
Ara-C 3 g/m2 every 12 hours days 1 and 2 and
mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-
Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and
mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from
infections during treatment-induced
cytopenia. The predominant toxicity was severe myelosuppression in all patients with major
infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory
Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-
drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic
growth factors will be evaluated in subsequent trials.