Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab

A 20-year retrospective follow-up study in patients with lymphoma

Corrado Tarella, Roberto Passera, Michele Magni, Fabio Benedetti, Andrea Rossi, Angela Gueli, Caterina Patti, Guido Parvis, Fabio Ciceri, Andrea Gallamini, Sergio Cortelazzo, Valerio Zoli, Paolo Corradini, Alessandra Carobbio, Antonino Mulé, Marco Bosa, Anna Barbui, Massimo Di Nicola, Marco Sorio, Daniele Caracciolo & 2 others Alessandro M. Gianni, Alessandro Rambaldi

Research output: Contribution to journalArticle

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Abstract

Purpose: High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. Patients and Methods: A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). Results: At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. Conclusion: This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.

Original languageEnglish
Pages (from-to)814-824
Number of pages11
JournalJournal of Clinical Oncology
Volume29
Issue number7
DOIs
Publication statusPublished - Mar 1 2011

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Autografts
Lymphoma
Drug Therapy
Neoplasms
Blood Cells
Stem Cells
B-Cell Lymphoma
Survival
Leukemia
Salvage Therapy
Rituximab
T-Cell Lymphoma
Cytarabine
Hodgkin Disease
Radiotherapy
Transplants
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab : A 20-year retrospective follow-up study in patients with lymphoma. / Tarella, Corrado; Passera, Roberto; Magni, Michele; Benedetti, Fabio; Rossi, Andrea; Gueli, Angela; Patti, Caterina; Parvis, Guido; Ciceri, Fabio; Gallamini, Andrea; Cortelazzo, Sergio; Zoli, Valerio; Corradini, Paolo; Carobbio, Alessandra; Mulé, Antonino; Bosa, Marco; Barbui, Anna; Di Nicola, Massimo; Sorio, Marco; Caracciolo, Daniele; Gianni, Alessandro M.; Rambaldi, Alessandro.

In: Journal of Clinical Oncology, Vol. 29, No. 7, 01.03.2011, p. 814-824.

Research output: Contribution to journalArticle

Tarella, C, Passera, R, Magni, M, Benedetti, F, Rossi, A, Gueli, A, Patti, C, Parvis, G, Ciceri, F, Gallamini, A, Cortelazzo, S, Zoli, V, Corradini, P, Carobbio, A, Mulé, A, Bosa, M, Barbui, A, Di Nicola, M, Sorio, M, Caracciolo, D, Gianni, AM & Rambaldi, A 2011, 'Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: A 20-year retrospective follow-up study in patients with lymphoma', Journal of Clinical Oncology, vol. 29, no. 7, pp. 814-824. https://doi.org/10.1200/JCO.2010.28.9777
Tarella, Corrado ; Passera, Roberto ; Magni, Michele ; Benedetti, Fabio ; Rossi, Andrea ; Gueli, Angela ; Patti, Caterina ; Parvis, Guido ; Ciceri, Fabio ; Gallamini, Andrea ; Cortelazzo, Sergio ; Zoli, Valerio ; Corradini, Paolo ; Carobbio, Alessandra ; Mulé, Antonino ; Bosa, Marco ; Barbui, Anna ; Di Nicola, Massimo ; Sorio, Marco ; Caracciolo, Daniele ; Gianni, Alessandro M. ; Rambaldi, Alessandro. / Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab : A 20-year retrospective follow-up study in patients with lymphoma. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 7. pp. 814-824.
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T2 - A 20-year retrospective follow-up study in patients with lymphoma

AU - Tarella, Corrado

AU - Passera, Roberto

AU - Magni, Michele

AU - Benedetti, Fabio

AU - Rossi, Andrea

AU - Gueli, Angela

AU - Patti, Caterina

AU - Parvis, Guido

AU - Ciceri, Fabio

AU - Gallamini, Andrea

AU - Cortelazzo, Sergio

AU - Zoli, Valerio

AU - Corradini, Paolo

AU - Carobbio, Alessandra

AU - Mulé, Antonino

AU - Bosa, Marco

AU - Barbui, Anna

AU - Di Nicola, Massimo

AU - Sorio, Marco

AU - Caracciolo, Daniele

AU - Gianni, Alessandro M.

AU - Rambaldi, Alessandro

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Y1 - 2011/3/1

N2 - Purpose: High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. Patients and Methods: A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). Results: At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. Conclusion: This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.

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