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

Craig H. Moskowitz, Stephen D. Nimer, Andrew D. Zelenetz, Tania Trippett, Eric E. Hedrick, Daniel A. Filippa, Diane Louie, Maria Gonzales, Janine Walits, Nancy Coady-Lyons, Jing Qin, Richard Frank, Joseph Bertino, Andre Goy, Ariela Noy, James P. O'Brien, David Straus, Carol S. Portlock, Joachim Yahalom

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)616-623
Number of pages8
JournalBlood
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2001

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Chemoradiotherapy
Etoposide
Stem cells
Hodgkin Disease
Refractory materials
Ifosfamide
Carboplatin
Fractionation
Chemotherapy
Disease-Free Survival
Radiotherapy
Stem Cell Transplantation
Survival Rate
Salvaging
Carmustine
Peptide Initiation Factors
Regression analysis
Cyclophosphamide
Dosimetry
Toxicity

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Moskowitz, Craig H. ; Nimer, Stephen D. ; Zelenetz, Andrew D. ; Trippett, Tania ; Hedrick, Eric E. ; Filippa, Daniel A. ; Louie, Diane ; Gonzales, Maria ; Walits, Janine ; Coady-Lyons, Nancy ; Qin, Jing ; Frank, Richard ; Bertino, Joseph ; Goy, Andre ; Noy, Ariela ; O'Brien, James P. ; Straus, David ; Portlock, Carol S. ; Yahalom, Joachim. / 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. In: Blood. 2001 ; Vol. 97, No. 3. pp. 616-623.
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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.",
author = "Moskowitz, {Craig H.} and Nimer, {Stephen D.} and Zelenetz, {Andrew D.} and Tania Trippett and Hedrick, {Eric E.} and Filippa, {Daniel A.} and Diane Louie and Maria Gonzales and Janine Walits and Nancy Coady-Lyons and Jing Qin and Richard Frank and Joseph Bertino and Andre Goy and Ariela Noy and O'Brien, {James P.} and David Straus and Portlock, {Carol S.} and Joachim Yahalom",
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Moskowitz, CH, Nimer, SD, Zelenetz, AD, Trippett, T, Hedrick, EE, Filippa, DA, Louie, D, Gonzales, M, Walits, J, Coady-Lyons, N, Qin, J, Frank, R, Bertino, J, Goy, A, Noy, A, O'Brien, JP, Straus, D, Portlock, CS & Yahalom, J 2001, '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', Blood, vol. 97, no. 3, pp. 616-623. https://doi.org/10.1182/blood.V97.3.616

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. / Moskowitz, Craig H.; Nimer, Stephen D.; Zelenetz, Andrew D.; Trippett, Tania; Hedrick, Eric E.; Filippa, Daniel A.; Louie, Diane; Gonzales, Maria; Walits, Janine; Coady-Lyons, Nancy; Qin, Jing; Frank, Richard; Bertino, Joseph; Goy, Andre; Noy, Ariela; O'Brien, James P.; Straus, David; Portlock, Carol S.; Yahalom, Joachim.

In: Blood, Vol. 97, No. 3, 01.02.2001, p. 616-623.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease

T2 - Analysis by intent to treat and development of a prognostic model

AU - Moskowitz, Craig H.

AU - Nimer, Stephen D.

AU - Zelenetz, Andrew D.

AU - Trippett, Tania

AU - Hedrick, Eric E.

AU - Filippa, Daniel A.

AU - Louie, Diane

AU - Gonzales, Maria

AU - Walits, Janine

AU - Coady-Lyons, Nancy

AU - Qin, Jing

AU - Frank, Richard

AU - Bertino, Joseph

AU - Goy, Andre

AU - Noy, Ariela

AU - O'Brien, James P.

AU - Straus, David

AU - Portlock, Carol S.

AU - Yahalom, Joachim

PY - 2001/2/1

Y1 - 2001/2/1

N2 - 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.

AB - 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.

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