Outcomes of EAM conditioned autologous haematopoietic SCT for lymphoma. A matched pairs retrospective single-centre study analysis

BEAM (BCNU, Etoposide, Cytarabine and Melphalan) chemotherapy followed by auto-SCT is superior to salvage chemotherapy alone, in patients with Hodgkin lymphoma (HL)1 and non-Hodgkin lymphoma (NHL)2 who have relapsed disease. However, BCNU is associated with potentially lethal pulmonary interstitial toxicity, in a dose-dependent manner.3 The incidence of BCNU-associated pneumonitis in published trials has ranged from 3% (ref. 1) to 17% (ref. 4), depending on definition, but the risk of pneumonitis in patients with pre-existing lung disease is unknown. Our practice has been to omit BCNU when pre-transplant lung function tests showed a lung carbon monoxide transfer coefficient (KCO) of less than 50% or when there was pre-existing lung disease. At our centre, between 2000 and 2010, 338 adults have been transplanted with BEAM conditioning, and 23 patients with an identical regimen but without BCNU (EAM). BEAM chemotherapy involved cumulative doses of BCNU at 300 mg/m2, etoposide at 800 mg/m2, cytarabine at 1600 mg/m2 and melphalan at 140 mg/m2. OS and PFS were estimated by the Kaplan–Meier method. OS was measured from the time of transplantation till death. PFS was measured from the time of transplantation till death or disease progression. A 1:1 matched-pair analysis, based on age and sex, was used to compare the outcomes of patients transplanted with a BEAM regimen to those with the EAM regimen. The log-rank test was used to compare differences between the survival distributions. The median age of the patients considered was 53 (range: 16–70). The median follow-up of the patients was 3.2 years. The two groups were evenly matched (Table 1), except for an increase in early-stage disease in the EAM cohort (n=10) compared with the BEAM cohort (n=4). Disease status and chemosensitivity of disease at the time of transplant were equally matched. Patients transplanted with EAM conditioning had worse survival, when compared with the group transplanted with BEAM. The EAM cohort had a median OS of 29 months, compared to 77 months for the matched BEAM cohort (P=0.03). For the EAM cohort, the median PFS was 11 months compared to 63 months for the patients treated with BEAM (P=0.02) (Figure 1). For both regimens, the 100-day TRM was identical at 8.7% (the overall 100-day TRM in the entire BEAM cohort of 338 patients was 5%). During the follow-up period, disease-related causes of death were 11 in the EAM group, compared to 6 in the BEAM group. Our analysis suggests that patients transplanted with EAM may have inferior survival compared with patients conditioned with the standard BEAM regimen, because of poorer disease control seen by the reduction in PFS and similar TRM rates. EAM conditioning was well tolerated in this cohort of patients with impaired lung function, as TRM was comparable for the two conditioning regimens. There might be an argument that the reduced lung function of these patients resulted in a lower intensity of treatment pre-transplant and a subsequent reduction in disease control prior to transplant. However this is not supported by our data, where the disease stage and status at transplant were similar for both treatment groups. Alternative management strategies for these patients may be to either lower thresholds for omitting BCNU, or substituting BCNU with an agent with less pulmonary toxicity. There is some suggestion that lomustine may have less pulmonary toxicity than BCNU.5, 6 Pavlu et al.5 and Perz et al.6 describe their experience with the use of LACE (lomustine, cytarabine, CY and etoposide) in the setting of relapsed or refractory HL and diffuse large B-cell lymphoma, and it appears to be well tolerated with no serious lung toxicity reported. However, this was only in the setting of patients without pre-existing lung disease. Indeed, in a cohort of reduced lung function, the use of lomustine (alongside CY and etoposide) appears to be associated with a significant degree of pulmonary toxicity,7 with 3 fatalities in 59 patients, from interstitial pneumonitis almost 1 year after transplant. Owing to a lack of a proven substitute for BCNU in this treatment setting, we have chosen to lower our KCO threshold for withholding BCNU, or use a dose reduction for these patients. Collaboration with other centres is required to determine whether our experience has been replicated elsewhere. The authors declare no conflict of interest.