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

Abstract

BACKGROUNDThe 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).METHODSData 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.RESULTSNinety‐two patients (90%) completed the HDS program. There were five toxic deaths (treatment‐related mortality rate, 4.9%) and six secondary malignan cies (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% 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.CONCLUSIONSThe 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. Cancer 2003;97:2748–59. © 2003 American Cancer Society.DOI 10.1002/cncr.11414

Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

“…The analysis of a Brazilian cohort has several implications because the frequency of some important poor prognostic factors, such as B symptoms and bulky disease, are higher in our patients compared to cohorts from the Northern Hemisphere. (15-17) In an Italian study (18) evaluating HDS in 102 patients with refractory or recurrent HL, 42% had B symptoms and 29% had bulky disease. In another study (19) evaluating the use of HDT and autologous HSCT in 494 Spanish patients with refractory or recurrent HL, 40.5% had B symptoms and 33% had bulky disease.…”

Allogeneic transplantation for Hodgkin’s lymphoma

“…About 50% of patients relapsing after first line therapy may be rescued by high-dose chemotherapy followed by autologous stem cell transplantation (autoSCT) (Josting et al, 2002(Josting et al, , 2005Schmitz et al, 2002;Tarella et al, 2003;Lavoie et al, 2005;Viviani et al, 2010). In particular, patients who experienced a late relapse after the first-line chemotherapy can do significantly better than those with primary refractory disease (survival of 70-80% versus 20-30%) (Lazarus et al, 1999;Sweetenham et al, 1999;Josting et al, 2005).…”

Lymphomas

“…Of these factors, one of the most powerful predictors of outcome after relapse is duration of fi rst remission, with signifi cantly inferior outcomes for patients who relapse within 12 months of completion of frontline therapy (Brice et al 1997 ;Josting et al 2000Josting et al , 2002a. Outcomes are particularly dismal for those who have disease refractory to primary therapy (Josting et al 2000 ;Tarella et al 2003 ). One prospective adult study of salvage chemotherapy followed by HDCT with autologous HCT identifi ed three factors at the time of relapse that predicted outcome (B symptoms, extranodal disease, and fi rst remission duration < 12 months) and documented EFS of 83 % for patients with zero or one risk factor and EFS of 10 % for those with three risk factors (Moskowitz et al 2001 ).…”