Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Arnon Nagler (1) , Myriam Labopin (2, 3) , Norbert Claude Gorin (4, 2, 3) , Felicetto Ferrara (5) , Miguel A. Sanz (6) , Depei Wu (7) , Antonio Torres Gomez (8) , Simona Lapusan (4) , Giuseppe Irrera (9) , Jose E. Guimaraes (10) , Aida Botelho Sousa (11) , Angelo Michele Carella (12) , Norbert Vey (13) , William Arcese (14) , Avichai Shimoni (1) , Raanan Berger (1) , Vanderson Rocha (15) , Mohamad Mohty (2, 3, 4)

1 Chaim Sheba Medical Center
2 Acute Leukemia Working Party of EBMT
3 UMRS893 - Centre de Recherche Saint-Antoine
4 CHU Saint-Antoine [AP-HP]
5 Ospedale Cardarelli
6 Hospital La Fe
7 Soochow University
8 Hospital Reina Sofia, Cordoba
9 Azienda Ospedaleria Universitaria di Modena = University Hospital of Modena
10 Hospital de São João [Porto]
11 Hospital de St. António dos Capuchos
12 UniGe - Università degli studi di Genova = University of Genoa
13 IPC - Institut Paoli-Calmettes
14 Rome transplant network
15 Churchill Hospital

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.

Domaines: Hématologie

Arnon Nagler, Myriam Labopin, Norbert Claude Gorin, Felicetto Ferrara, Miguel A. Sanz, et al.. Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica, 2014, 99 (8), pp.1380-1386. ⟨10.3324/haematol.2014.105197⟩. ⟨hal-01325444⟩