Intravenous Busulphan in Combination with ETOPOSIDE and MELPHALAN Used as Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Lymphomas: Evaluation of Toxicity and Efficacy
Authors: Mallouri Despina , Sakellari Ioanna , Batsis Ioannis , Konstantinou Varnavas , Baliakas Panayotis , Antoniou Athanasios , Apostolou Chrisa , Anagnostopoulos Achilles , Fassas Athanasios 
Published: October 2019

Abstract
Abstract 1324
The standard conditioning regimen used in autologous hematopoietic cell transplantation (autoHCT) for lymphomas is BEAM. During the last year, due to Carmustine (BCNU) unavailability, a new alternative conditioning regimen was designed in our unit consisting of intravenous Busulphan (Busilvex) (3.2mg/kg/day for 3 days), Etoposide (400mg/m̂2/day for 2 days) and Melphalan (140mg/m̂2) (BEM). We retrospectively evaluated the safety and efficacy of the above regimen in 25 patients, aged 30 (16- 65) years, transplanted for Hodgkin (14) and non Hodgkin Lymphomas (DLBCL 7; large B cell mediastinal 1; T-anaplastic 2; MCL 1) between May 2009 and July 2010. The patients received a median of 3 (2- 8) lines of treatment before autoHCT. Disease was chemosensitive to pretransplantation salvage treatment in 17 [6/25 achieved complete remission (24%)], stable in 2 and refractory in 6 patients. According to the Hematopoietic cell transplantation specific comorbidity index, 20 were low (score 0) and 5 intermediate (score 1) risk. Fifteen patients received palifermin and all received cotrimoxazole, antifungal, antiviral and antibiotics as prophylaxis for at least 3 months. The median CD34+ cell dose was 5.59 (2.1- 19.59) ×106̂/Kg and patients received GCSF for a median of 10 (7- 53) days. Prompt engraftment was achieved in 23/25 patients. The median time for neutrophil engraftment (> 500/mm̂3) was day +11 (9- 29), +14 (9- 150) for platelet (>20000/mm̂3) and +11 (8- 43) for erythroid (red blood cell transfusion independency) in 24/25 patients. A second transplantation with double cord blood was offered in one patient because of engraftment failure. In one patient stable engraftment was achieved after a second infusion of autologous cells due to delayed engraftment. The median number of red blood cell transfusions were 3 (0- 15), median single donor platelet units were 4 (0- 36). No red blood cell and no platelet transfusions were required in 4 and 2 patients respectively. Infection (grade II-III) during neutropenia developed in 19 patients (bacteremias mostly; no fungal or respiratory infections). Patients were febrile for a median of 3 (1- 43) days. Twenty-four patients developed mucositis (grade I 6, II 8, III 10) and 21 received parenteral nutrition for 5 (1- 12) days. Nineteen developed liver and gastrointestinal toxicity (elevation of transaminases, nausea/vomiting) grade I- III (grade I 4, grade II 11, grade III 4). The median day of discharge was +15 (10- 32) in 24/25 patients. The patient allografted post autoHCT died at day +63 due to refractory disease and multiple infections. The median follow-up was 7.1 (3-16) months. Eleven patients (44%) were in complete remission (CR) at disease evaluation by CTs one month post autoHCT, without any further treatment. All of them had chemosensitive disease. At last follow up 22 patients are alive and 17 in CR. Three patients succumbed to their disease. The estimated 2-year overall survival (OS) is 90% and disease free survival (DFS) is 60% (95% for patients with chemosensitive disease and 15% for refractory, p<0.05). Despite of the limitations of this study with a small number of patients and short follow up period, the toxicity of the conditioning regimen (BEM) seems to be acceptable and comparable to widely used regimens and offers promising results. For patients with chemosensitive disease BEM seems to be efficacious providing high rates of OS and DFS.

Disclosures:
No relevant conflicts of interest to declare.