PATTERNS OF FAILURE FOLLOWING HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION WITH INVOLVED FIELD RADIOTHERAPY FOR RELAPSED REFRACTORY HODGKINS-DISEASE

Purpose: To evaluate the patterns of failure and outcome of patients undergoing high-dose chemotherapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease with emphasis on the impact of involved-field radiotherapy. Method and Materials: Fifty-four adult patients with refractory (25) or relapsed (29) Hodgkin's disease underwent high-dose chemotherapy with either autologous bone marrow (32) or peripheral stem cell (23) transplantation. Twenty patients received involved-field radiotherapy either prior to (7) or following (13) high-dose chemotherapy. Patients treated prior to the high-dose chemotherapy received radiation to bulky or symptomatic sites, and those treated following the transplantation were treated to sites of disease persistence (10) or to consolidate a complete response (3). Twenty-six patients had purely nodal disease, 10 had lung involvement, 7 liver, 5 bone, and 3 bone marrow. A total of 147 sites were present prior to high-dose chemotherapy. Nineteen were bulky (greater than or equal to 5 cm), and 42 arose in a previous radiotherapy field. Results: Twenty-five of the 54 patients (46.3%) relapsed. Seventeen (68.0%) relapsed in sites of disease present prior to high-dose chemotherapy. Patients treated with involved-field radiotherapy had a lower rate of relapse in sites of prior disease involvement (26.3 vs. 42.8%) (p < 0.05) than those not treated with radiotherapy. Twenty-one patients had disease persistence following high-dose chemotherapy, of which 10 received involved-field radiotherapy and were converted to a complete response. Patients with disease persistence who received involved-held radiotherapy had a better progression-free survival (40.0 vs. 12.1%) (p = 0.04) than those who did not. Moreover, the patients converted to a complete response had similar progression-free and cause-specific survival as those patients achieving a complete response with high-dose chemotherapy alone. Of the initial 147 sites, 143 (97.3%) were amenable to involved-field radiation therapy, The addition of involved-field radiotherapy improved the 5-year local control of all sites (p = 0.008), nodal sites (p = 0.01), and sites of disease persistence (p = 0.0009). Conclusions: Patients with relapsed/refractory Hodgkin's disease undergoing high-dose chemotherapy and autologous bone marrow rescue have a high rate of relapse in sites of prior disease involvement, Involved-field radiotherapy is capable of improving the control of these sites, the majority of which are amenable to radiotherapy. In addition, the use of radiotherapy to sites of disease persistence following high-dose chemotherapy may improve the outcome of these patients.