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High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission.

Abstract
Complete remission rates of 70-90% can be achieved following combination chemotherapy for patients with advanced-stage Hodgkin's disease (HD). Patients who present with unfavorable poor prognostic factors, however, have a 5-year disease-free survival of only 40-50%. In an attempt to improve the prognosis of 20 patients with poor-risk advanced-stage HD, we evaluated the role of early high-dose therapy (HDT) and autologous bone marrow/stem cell transplantation (ASCT) during the first complete or partial remission (CR/PR). Patients were eligible for ASCT if they either achieved a PR (defined as > 50% regression) (six patients), or achieved a CR (14 patients) but had presented with three or more of the following unfavorable features: stage IV disease with bone marrow involvement or > or = 2 extranodal sites of involvement; bulky mass > 10 cm or bulky mediastinal mass > 1/3 of mediastina/thoracic ratio; B symptoms; and elevated serum lactate dehydrogenase (LDH) level. The study included 11 men (55%) and 9 women (45%). The median age was 37 years (range 20-57). Seventeen patients (85%) had stage IV disease; 14 (70%) had B symptoms; 13 (65%) had bulky mass > 10 cm; 14 (70%) had > or = 2 extra nodal sites involvement; and eight patients (40%) had elevated LDH levels. All patients were treated with standard four or 7-8 drug combination chemotherapy regimens until they achieved maximal response prior to ASCT with a median of six cycles (range 4-11). Six patients also received involved field radiotherapy to residual bulky mass > 5 cm or bony lesions before ASCT. The median time from diagnosis to ASCT was 8.6 months (range 5.5-18.9). Preparative regimens consisted of fractionated total body irradiation (FTBI) 1200 cGy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in all patients except one who had borderline pulmonary function and received lomustine 15 mg/kg instead of FTBI. All patients engrafted and there was no transplant-related mortality. One patient developed congestive cardiomyopathy at 4 years post-ASCT. All patients remain alive and in remission at a median follow-up of 42.8 months (range, 13.2-149.2). These preliminary results suggest that HDT and ASCT can be performed safely during first CR/PR in selected patients with advanced-stage HD who have an unfavorable prognosis. Further randomized studies comparing HDT and ASCT during first CR with conventional chemotherapy and ASCT at relapse in poor-risk advanced-stage HD should be conducted. The prognostic factors and risk groups described recently by an international prognostic study can be used to identify high-risk patients who may be candidates for more intensive therapy.
AuthorsA Nademanee, A Molina, H Fung, A Stein, P Parker, I Planas, M R O'Donnell, D S Snyder, A Kashyap, R Spielberger, R Bhatia, A Krishnan, I Sniecinski, N Vora, M Slovak, A Dagis, J C Niland, S J Forman
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 5 Issue 5 Pg. 292-8 ( 1999) ISSN: 1083-8791 [Print] United States
PMID10534059 (Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Topics
  • Adult
  • Bone Marrow Transplantation
  • Combined Modality Therapy
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Hodgkin Disease (drug therapy, radiotherapy, therapy)
  • Humans
  • Male
  • Middle Aged
  • Remission Induction
  • Risk Factors
  • Survival Rate
  • Transplantation, Autologous
  • Whole-Body Irradiation

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