A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi.

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.

Antineoplastic drug-induced bradyarrhythmias.

INTRODUCTION: Cardiac injury is one of the most impairing side effects of anticancer treatment. The extension of the range of available drugs, the use of combination regimens and the association with radiation therapy have improved life expectancy; however, they have also caused a rising typology of cardiac toxicities, including not only congestive heart failure, but also myocardial ischemia, thromboembolism, hypertension and arrhythmias. AREAS COVERED: The aim of this review is to describe the evidence of association between bradyarrhythmias and antineoplastic agents, including chemotherapeutic and molecular-targeted drugs in the adult population, to summarize the possible mechanisms of onset and to make suggestions for clinical management. A Medline search for each anticancer agent and associated cardiotoxic, electrocardiographic and arrhythmic alteration was performed for the years January 1970 - January 2012. A cross-referencing search from identified studies was also carried out. Published reports from clinical trials, non-randomized studies, case reports and recent reviews were considered. Only agents with a specific relation to bradyarrhythmias were included and are discussed. EXPERT OPINION: A greater knowledge of this specific cardiac toxicity may help appropriate risk stratification and correct management during treatment and follow-up. The exchange of information among hematologists, oncologists and cardiologists is essential for this purpose.

Early and long-term engraftment after autologous peripheral stem cell transplantation in acute myeloid leukemia patients.

This study aimed to identify which subset of CD34+ cells might be the most predictive of early and long-term hematopoietic recovery following autologous peripheral blood stem cell (PBSC) transplantation (PBSCT) in adult acute myeloid leukemia (AML) patients. The relationships between the number of 'mature' subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD90-) and 'immature' subsets of CD34+ cells (CD34+/CD33-, CD34+/CD38-, CD34+/DR- and CD34+/CD90+) and early and long-term hemoglobin, neutrophil and platelet counts were studied in a homogeneous series (for disease, pre-transplant chemotherapy, mobilization chemotherapy, conditioning regimen) of 26 AML patients after autologous PBSCT. Cell counts were performed before and after cryopreservation, but only after thawing were the cell counts used for correlation with early and long-term engraftment. The number of CD34+/CD38- cells infused correlated with the neutrophil (r = 0.88, p < 0.005) and platelet counts (r = 0.67, p < 0.05) at 12 months after PBSCT. This correlation was better than that for the total CD34+ cell dose at 12 months (r = 0.36, p = 0.09 for neutrophil count and r = 0.48, p = 0.06 for platelets count). The number of CD34+/CD90+ cells was also correlated with the platelet counts at 6 (r = 0.70, p < 0.05) and 12 months (r = 0.80, p = 0.005) after PBSCT. This correlation was better than the total dose of CD34+ cells at 6 (r = 0.31, p = 0.3) and 12 months (r = 0.48, p = 0.06) for the platelet counts. CD34+ subset analysis suggests that for early engraftment the total number of CD34+ cells infused is more strongly correlated than the CD34+ subsets, whereas the CD34+/CD38- and CD34+/CD90+ subsets may be associated with sustained long-term neutrophil and platelet engraftment. These findings may help to predict the repopulating capacity of PBSCs in AML patients after autologous PBSCT, especially when a relatively low number of CD34+ cells is infused.