A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: Analysis by intent to treat and development of a prognostic model Journal Article


Authors: Moskowitz, C. H.; Nimer, S. D.; Zelenetz, A. D.; Trippett, T.; Hedrick, E. E.; Filippa, D. A.; Louie, D.; Gonzales, M.; Walits, J.; Coady-Lyons, N.; Qin, J.; Frank, R.; Bertino, J. R.; Goy, A.; Noy, A.; O'Brien, J.; Straus, D.; Portlock, C. S.; Yahalom, J.
Article Title: A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: Analysis by intent to treat and development of a prognostic model
Abstract: Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT. © 2001 by The American Society of Hematology.
Keywords: adolescent; adult; cancer survival; child; school child; treatment outcome; disease-free survival; middle aged; survival rate; human cell; major clinical study; salvage therapy; cisplatin; dose response; drug efficacy; multimodality cancer therapy; drug megadose; carboplatin; models, biological; etoposide; antineoplastic combined chemotherapy protocols; drug administration schedule; relapse; recurrence; cyclophosphamide; stem cell transplantation; hematopoietic stem cell transplantation; carmustine; ifosfamide; hodgkin disease; stem cell; radiation dose fractionation; dose fractionation; regression analysis; lymph node irradiation; leukemia remission; autotransplantation; lymphatic irradiation; humans; prognosis; human; male; female; priority journal; article
Journal Title: Blood
Volume: 97
Issue: 3
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2001-02-01
Start Page: 616
End Page: 623
Language: English
DOI: 10.1182/blood.V97.3.616
PUBMED: 11157476
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Joachim Yahalom
    407 Yahalom
  2. Carol Portlock
    181 Portlock
  3. Craig Moskowitz
    375 Moskowitz
  4. Ariela Noy
    208 Noy
  5. James O'Brien
    17 O'Brien
  6. Diane C Louie
    49 Louie
  7. Richard C Frank
    21 Frank
  8. Eric E Hedrick
    16 Hedrick
  9. Joseph Bertino
    270 Bertino
  10. Jing Qin
    86 Qin
  11. Nancy Coady Lyons
    8 Lyons
  12. Andrew D Zelenetz
    556 Zelenetz
  13. Stephen D Nimer
    345 Nimer
  14. Daniel A Filippa
    102 Filippa
  15. David J Straus
    213 Straus
  16. Andre Goy
    28 Goy
  17. Janine   Walits
    2 Walits