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

Auayporn Nademanee, Arturo Molina, Henry Fung, Anthony Stein, Pablo Parker, Ina Planas, Margaret R. O'Donnell, David S. Snyder, Ashwin Kashyap, Ricardo Spielberger, Ravi Bhatia, Amrita Krishnan, Irena Sniecinski, Nayana Vora, Marilyn Slovak, Andrew Dagis, Joyce C. Niland, Stephen J. Forman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 ≥2 extranodal sites of involvement; bulky mass >10 cm or bulky mediastinal mass >1/3 of mediastinal/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 ≥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.

Original languageEnglish
Pages (from-to)292-298
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume5
Issue number5
DOIs
StatePublished - Oct 1 1999

Keywords

  • 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
  • Humans
  • Male
  • Middle Aged
  • Remission Induction
  • Risk Factors
  • Survival Rate
  • Transplantation, Autologous
  • Whole-Body Irradiation

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