Intravenous Busulphan in Combination with ETOPOSIDE and MELPHALAN Used as Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Lymphomas: Evaluation of Toxicity and Efficacy

Despina Mallouri1*, Ioanna Sakellari2*, Ioannis Batsis2*, Varnavas Konstantinou1*, Panayotis Baliakas1*, Athanasios Antoniou1*, Chrisa Apostolou1*, Achilles Anagnostopoulos3 and Athanasios Fassas1*

Author address: 

1Hematology - BMT unit, G .Papanicolaou Hospital, Thessaloniki, Greece 2Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece 3Hematology - BMT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece


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/m^2/day for 2 days) and Melphalan (140mg/m^2) (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) x 10^6/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/mm^3) was day +11 (9- 29), +14 (9- 150) for platelet (>20000/mm^3) 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

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Full conference title: 

52nd American Society of Haematologists Annual Meeting
    • ASH 52nd (2010)