Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma

Patrick J. Stiff, Joseph M. Unger, James R. Cook, Louis S. Constine, Stephen Couban, Douglas A. Stewart, Thomas C. Shea, Pierluigi Porcu, Jane N. Winter, Brad S. Kahl, Thomas P Miller, Raymond R. Tubbs, Deborah Marcellus, Jonathan W. Friedberg, Kevin P. Barton, Glenn M. Mills, Michael LeBlanc, Lisa M Rimsza, Stephen J. Forman, Richard I. Fisher

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Abstract

BACKGROUND: The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. METHODS: We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. RESULTS: Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P = 0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P = 0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation.

Original languageEnglish (US)
Pages (from-to)1681-1690
Number of pages10
JournalNew England Journal of Medicine
Volume369
Issue number18
DOIs
StatePublished - 2013

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Autologous Transplantation
Non-Hodgkin's Lymphoma
Transplantation
Control Groups
Disease-Free Survival
Stem Cell Transplantation
Induction Chemotherapy
Survival Rate
Survival
Confidence Intervals
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Disease Progression
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stiff, P. J., Unger, J. M., Cook, J. R., Constine, L. S., Couban, S., Stewart, D. A., ... Fisher, R. I. (2013). Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. New England Journal of Medicine, 369(18), 1681-1690. https://doi.org/10.1056/NEJMoa1301077

Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. / Stiff, Patrick J.; Unger, Joseph M.; Cook, James R.; Constine, Louis S.; Couban, Stephen; Stewart, Douglas A.; Shea, Thomas C.; Porcu, Pierluigi; Winter, Jane N.; Kahl, Brad S.; Miller, Thomas P; Tubbs, Raymond R.; Marcellus, Deborah; Friedberg, Jonathan W.; Barton, Kevin P.; Mills, Glenn M.; LeBlanc, Michael; Rimsza, Lisa M; Forman, Stephen J.; Fisher, Richard I.

In: New England Journal of Medicine, Vol. 369, No. 18, 2013, p. 1681-1690.

Research output: Contribution to journalArticle

Stiff, PJ, Unger, JM, Cook, JR, Constine, LS, Couban, S, Stewart, DA, Shea, TC, Porcu, P, Winter, JN, Kahl, BS, Miller, TP, Tubbs, RR, Marcellus, D, Friedberg, JW, Barton, KP, Mills, GM, LeBlanc, M, Rimsza, LM, Forman, SJ & Fisher, RI 2013, 'Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma', New England Journal of Medicine, vol. 369, no. 18, pp. 1681-1690. https://doi.org/10.1056/NEJMoa1301077
Stiff, Patrick J. ; Unger, Joseph M. ; Cook, James R. ; Constine, Louis S. ; Couban, Stephen ; Stewart, Douglas A. ; Shea, Thomas C. ; Porcu, Pierluigi ; Winter, Jane N. ; Kahl, Brad S. ; Miller, Thomas P ; Tubbs, Raymond R. ; Marcellus, Deborah ; Friedberg, Jonathan W. ; Barton, Kevin P. ; Mills, Glenn M. ; LeBlanc, Michael ; Rimsza, Lisa M ; Forman, Stephen J. ; Fisher, Richard I. / Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 18. pp. 1681-1690.
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abstract = "BACKGROUND: The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. METHODS: We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. RESULTS: Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55{\%}, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95{\%} confidence interval [CI], 1.18 to 2.51; P = 0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71{\%}, respectively (hazard ratio, 1.26; 95{\%} CI, 0.82 to 1.94; P = 0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82{\%} in the transplantation group and 64{\%} in the control group. CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation.",
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T1 - Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma

AU - Stiff, Patrick J.

AU - Unger, Joseph M.

AU - Cook, James R.

AU - Constine, Louis S.

AU - Couban, Stephen

AU - Stewart, Douglas A.

AU - Shea, Thomas C.

AU - Porcu, Pierluigi

AU - Winter, Jane N.

AU - Kahl, Brad S.

AU - Miller, Thomas P

AU - Tubbs, Raymond R.

AU - Marcellus, Deborah

AU - Friedberg, Jonathan W.

AU - Barton, Kevin P.

AU - Mills, Glenn M.

AU - LeBlanc, Michael

AU - Rimsza, Lisa M

AU - Forman, Stephen J.

AU - Fisher, Richard I.

PY - 2013

Y1 - 2013

N2 - BACKGROUND: The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. METHODS: We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. RESULTS: Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P = 0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P = 0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation.

AB - BACKGROUND: The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. METHODS: We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. RESULTS: Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P = 0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P = 0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation.

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