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
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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 -