Long-Term Outcome after LACE (Lomustine, Ara-C, Cyclophosphamide, Etoposide) Conditioned Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Lymphoma: A Single Centre Experience.

Introduction: The majority of patients with Hodgkin’s lymphoma are cured with initial therapy. However, in patients with primary refractory or relapsed disease, high-dose therapy followed by autologous stem cell transplantation has been shown to be the best option. We analysed patients (pts) who underwent autologous stem cell transplantation (ASCT) following LACE (Lomustine 200 mg/m2, Ara-C 4 g/m2, Cyclophosphamide 4.8 g/m2, Etoposide 1 g/m2) conditioning for relapsed or refractory Hodgkin’s lymphoma at the Hammersmith Hospital, London, between 1991 and 2004.

Patients and methods: 67 pts (46 m, 21 f) initially diagnosed with Hodgkin’s lymphoma (stage I; n=2, stage II; n=29, stage III; n=22 and stage IV; n=14) received first-line chemotherapy with ABVD or COP/ABVD (n=20), BEMOP-CA (n=29), COPP or similar (n=14) or mantle radiotherapy alone (n=4). High dose chemotherapy (HDC) with LACE and ASCT was undertaken in 45 of these pts in 1st relapse, 15 pts in 2nd or subsequent relapse and 7 pts with refractory disease. Median age at the time of HDC was 32 y (17 – 70 y). Prior to ASCT further chemotherapy achieved a complete or partial remission in 41 pts (chemosensitive), but 26 pts had no significant response (chemoresistant). Stem cells were mobilised with Etoposide (1.8 g/m²) and G-CSF in 56 pts, and bone marrow harvest was performed in the other 11 pts.

Results: Two pts suffered a treatment-related mortality (TRM) within the first 100 days (3%). Two pts (3%) developed secondary malignancy (acute myeloid leukaemia). With a median follow-up of 43.3 months (range 0.5 – 145.5 months) the cumulative probabilities of overall survival (OS) and progression free survival (PFS) at both 5 and 10 years was 70% and 62% respectively. Pts who had chemosensitive disease at the time of ASCT had a better OS (p=0.008) and PFS (p=0.08) when compared with pts who had chemoresistant disease. Median PFS has not yet been reached for chemosensitive pts but was 23.4 months for chemoresistant pts. Median OS has not yet been reached for either group.

Conclusions: The outcome for patients with relapsed or refractory Hodgkin’s lymphoma following high dose chemotherapy and ASCT has been sufficiently encouraging to suggest that ASCT should be considered early in chemosensitive patients. However, new therapeutic strategies are needed to improve the clinical outcome of patients with chemoresistant disease.