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High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral ( n = 468) or IV ( n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse ( P = 0·01), RFS ( P = 0·002) and OS ( P = 0·001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study. [ABSTRACT FROM AUTHOR]

High-dose busulfan (Bu) is an integral component of commonly used preparative regimens for both allogeneic and autologous transplantation. There is significant interest in comparing the efficacy and toxicity of administering Bu every 6 (Bu6) or every 24 hours (daily Bu). To facilitate a therapeutic dose-monitoring protocol, we transitioned from Bu6 to daily Bu dosing for patients with Hodgkin and non-Hodgkin lymphoma undergoing autologous stem cell transplantation (ASCT). Here, we retrospectively review outcomes of 400 consecutive eligible lymphoma patients who underwent ASCT from 2007 to 2013 with high-dose busulfan (Bu), cyclophosphamide (Cy), and etoposide (E). Bu was given at a fixed dose of either .8 mg/kg every 6 hours for 14 doses for 307 patients or a fixed dose of 2.8 mg/kg every 24 hours for 4 doses (days −9 through −6) for 93 patients who underwent transplantation after the transition from Bu6 to daily Bu was made. Toxicity was assessed using pulmonary and liver function tests (LFT) at specified time points before and after ASCT. Baseline patient and disease characteristics of patients dosed with Bu6 and daily Bu were similar. There was no significant difference in forced expiratory volume in 1 second or diffusing capacity of the lungs for carbon monoxide before and after transplantation in the Bu6 versus daily Bu cohorts. Changes in LFTs with daily Bu were not significantly different than those with Bu6. There were no differences in relapse, nonrelapse mortality, progression-free survival, or overall survival between Bu6 and Bu 24 administration schedules in univariable or multivariable analysis ( P  ≥ .34). For a subset of 23 patients who had first-dose Bu levels measured, we observed significant variation in an median estimated cumulative area under the curve (AUC) of 17,568 µM-minute (range, 12,104 µM-23,084 µM-minute). In conclusion, daily Bu with Cy/E is more convenient than Bu6, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 13%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring of Bu. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for eligible patients with multiple myeloma. Health care disparities can influence transplantation outcomes. However, the association of socioeconomic status (SES), a major indicator of health care disparities, with outcomes in patients with myeloma after AHCT has not been previously described. We analyzed 346 consecutive AHCT recipients with myeloma who underwent transplantation between 2003 and 2013 in this retrospective cohort study. Zip code of residence at the time of AHCT was obtained to assess annual household income based on 2010 US census data (median, $49,054; range, $16,546 to $127,313). SES groups were divided into < $45,000 (low; n = 120), $45,000 to $60,000 (middle; n = 116), and > $60,000 (high; n = 110). The low-income cohort had smallest portion of Caucasians (69% versus 89% versus 91%); otherwise, patient, disease, and transplantation characteristics were comparable among cohorts or different without significant patterns found. Median follow-up was 49 months. There was no difference among SES groups in overall survival, progression-free survival, nonrelapse mortality, or relapse in univariate and multivariable analysis. Similarly, SES was not associated with survival in a subset analysis of 303 patients who had survived for 1 year after transplantation. [ABSTRACT FROM AUTHOR]