Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review

Abstract

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.

Bendamustine‐based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers

“…The median time for neutrophils and platelets to engraft were 10 (range 0–98) and 11 days (range 0–210), respectively. Comparable engraftment results have been reported with carmustine, busulfan or thiotepa‐based conditioning . The median hospital stay duration was 23 days (range 12–85) with a BeEAM regimen.…”

“…The NRM of thiotepa‐based conditioning varied from 0% to 18%, depending on the thiotepa dose and the type of drug combination (thiotepa, cyclophosphamide, busulfan). In the largest study including more than 100 patients, involving treatment with a busulfan‐based conditioning regimen, an NRM of less than 5% was also reported (For a review see Damaj et al).…”

“…The median hospital stay duration was 23 days (range 12–85) with a BeEAM regimen. The median length of a hospital stay in studies including other lymphoma‐conditioning regimens ranged between 23 and 28 days …”

BEAM vs FEAM high-dose chemotherapy: retrospective study in lymphoma patients undergoing autologous stem cell transplant

“…The most widely used high-dose chemotherapy (HDC) before autologous stem cell transplant (ASCT) is BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) [1,2], which is considered the gold standard both in United States and Europe [3,4]. However, carmustine has been often substituted by other molecules due to its difficult supplying and high costs [3,5].…”

“…The most widely used high-dose chemotherapy (HDC) before autologous stem cell transplant (ASCT) is BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) [1,2], which is considered the gold standard both in United States and Europe [3,4]. However, carmustine has been often substituted by other molecules due to its difficult supplying and high costs [3,5]. In Italy, the most frequently used alternative regimen is FEAM (fotemustine, etoposide, cytarabine, melphalan), in which carmustine is replaced by fotemustine, a third-generation chloroethyl-nitrosourea with ability to cross the blood-brain barrier and a more favorable pulmonary toxicity profile, however not available in all European countries [6].…”