High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence

Corrado Tarella, Alessandra Cuttica, Umberto Vitolo, Marina Liberati, Massimo Di Nicola, Sergio Cortelazzo, Rosalba Rosato, Carlo Rosanelli, Nicola Di Renzo, Maurizio Musso, Enzo Pavone, Gino Santini, Alessandra Pescarollo, Alberto De Crescenzo, Massimo Federico, Andrea Gallamini, Patrizia Pregno, Roberta Romano, Paolo Coser, Eugenio GalloMario Boccadoro, Tiziano Barbui, Alessandro Pileri, Alessandro M. Gianni, Alessandro Levis

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

BACKGROUND. The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS. Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment- related mortality rate, 4.9%) and six secondary malignancies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% (95070 confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.

Original languageEnglish
Pages (from-to)2748-2759
Number of pages12
JournalCancer
Volume97
Issue number11
DOIs
Publication statusPublished - Jun 1 2003

Fingerprint

Autologous Transplantation
Hodgkin Disease
Multicenter Studies
Disease-Free Survival
Blood Cells
Stem Cells
Recurrence
Drug Therapy
Confidence Intervals
Survival
Mitoxantrone
Melphalan
Poisons
Myelodysplastic Syndromes
Etoposide
Therapeutics
Phenylalanine

Keywords

  • Clinical outcome
  • High-dose chemotherapy
  • Hodgkin lymphoma
  • Multicenter trial
  • Peripheral blood progenitor cell autograft

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma : A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. / Tarella, Corrado; Cuttica, Alessandra; Vitolo, Umberto; Liberati, Marina; Di Nicola, Massimo; Cortelazzo, Sergio; Rosato, Rosalba; Rosanelli, Carlo; Di Renzo, Nicola; Musso, Maurizio; Pavone, Enzo; Santini, Gino; Pescarollo, Alessandra; De Crescenzo, Alberto; Federico, Massimo; Gallamini, Andrea; Pregno, Patrizia; Romano, Roberta; Coser, Paolo; Gallo, Eugenio; Boccadoro, Mario; Barbui, Tiziano; Pileri, Alessandro; Gianni, Alessandro M.; Levis, Alessandro.

In: Cancer, Vol. 97, No. 11, 01.06.2003, p. 2748-2759.

Research output: Contribution to journalArticle

Tarella, C, Cuttica, A, Vitolo, U, Liberati, M, Di Nicola, M, Cortelazzo, S, Rosato, R, Rosanelli, C, Di Renzo, N, Musso, M, Pavone, E, Santini, G, Pescarollo, A, De Crescenzo, A, Federico, M, Gallamini, A, Pregno, P, Romano, R, Coser, P, Gallo, E, Boccadoro, M, Barbui, T, Pileri, A, Gianni, AM & Levis, A 2003, 'High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence', Cancer, vol. 97, no. 11, pp. 2748-2759. https://doi.org/10.1002/cncr.11414
Tarella, Corrado ; Cuttica, Alessandra ; Vitolo, Umberto ; Liberati, Marina ; Di Nicola, Massimo ; Cortelazzo, Sergio ; Rosato, Rosalba ; Rosanelli, Carlo ; Di Renzo, Nicola ; Musso, Maurizio ; Pavone, Enzo ; Santini, Gino ; Pescarollo, Alessandra ; De Crescenzo, Alberto ; Federico, Massimo ; Gallamini, Andrea ; Pregno, Patrizia ; Romano, Roberta ; Coser, Paolo ; Gallo, Eugenio ; Boccadoro, Mario ; Barbui, Tiziano ; Pileri, Alessandro ; Gianni, Alessandro M. ; Levis, Alessandro. / High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma : A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. In: Cancer. 2003 ; Vol. 97, No. 11. pp. 2748-2759.
@article{a5986f35ad2344da859ff98228769c8a,
title = "High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence",
abstract = "BACKGROUND. The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS. Ninety-two patients (90{\%}) completed the HDS program. There were five toxic deaths (treatment- related mortality rate, 4.9{\%}) and six secondary malignancies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64{\%} (95{\%} (95070 confidence interval [95{\%} CI], 54-74{\%}) and 53{\%} (95{\%} CI, 43-63{\%}), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77{\%} (95{\%} CI, 66-88{\%}) and 63{\%} (95{\%} CI, 50-76{\%}), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36{\%} (95{\%} CI, 16-55{\%}) and 33{\%} (95{\%} CI, 14-52{\%}), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.",
keywords = "Clinical outcome, High-dose chemotherapy, Hodgkin lymphoma, Multicenter trial, Peripheral blood progenitor cell autograft",
author = "Corrado Tarella and Alessandra Cuttica and Umberto Vitolo and Marina Liberati and {Di Nicola}, Massimo and Sergio Cortelazzo and Rosalba Rosato and Carlo Rosanelli and {Di Renzo}, Nicola and Maurizio Musso and Enzo Pavone and Gino Santini and Alessandra Pescarollo and {De Crescenzo}, Alberto and Massimo Federico and Andrea Gallamini and Patrizia Pregno and Roberta Romano and Paolo Coser and Eugenio Gallo and Mario Boccadoro and Tiziano Barbui and Alessandro Pileri and Gianni, {Alessandro M.} and Alessandro Levis",
year = "2003",
month = "6",
day = "1",
doi = "10.1002/cncr.11414",
language = "English",
volume = "97",
pages = "2748--2759",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma

T2 - A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence

AU - Tarella, Corrado

AU - Cuttica, Alessandra

AU - Vitolo, Umberto

AU - Liberati, Marina

AU - Di Nicola, Massimo

AU - Cortelazzo, Sergio

AU - Rosato, Rosalba

AU - Rosanelli, Carlo

AU - Di Renzo, Nicola

AU - Musso, Maurizio

AU - Pavone, Enzo

AU - Santini, Gino

AU - Pescarollo, Alessandra

AU - De Crescenzo, Alberto

AU - Federico, Massimo

AU - Gallamini, Andrea

AU - Pregno, Patrizia

AU - Romano, Roberta

AU - Coser, Paolo

AU - Gallo, Eugenio

AU - Boccadoro, Mario

AU - Barbui, Tiziano

AU - Pileri, Alessandro

AU - Gianni, Alessandro M.

AU - Levis, Alessandro

PY - 2003/6/1

Y1 - 2003/6/1

N2 - BACKGROUND. The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS. Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment- related mortality rate, 4.9%) and six secondary malignancies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% (95070 confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.

AB - BACKGROUND. The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS. Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment- related mortality rate, 4.9%) and six secondary malignancies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% (95070 confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.

KW - Clinical outcome

KW - High-dose chemotherapy

KW - Hodgkin lymphoma

KW - Multicenter trial

KW - Peripheral blood progenitor cell autograft

UR - http://www.scopus.com/inward/record.url?scp=0038182732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038182732&partnerID=8YFLogxK

U2 - 10.1002/cncr.11414

DO - 10.1002/cncr.11414

M3 - Article

C2 - 12767087

AN - SCOPUS:0038182732

VL - 97

SP - 2748

EP - 2759

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 11

ER -