Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

Marie Luise Hütter-Krönke, Axel Benner, Konstanze Döhner, Jürgen Krauter, Daniela Weber, Margit Moessner, Claus Henning Köhne, Heinz A. Horst, Ingo G.H. Schmidt-Wolf, Mathias Rummel, Katharina Götze, Elisabeth Koller, Andreas L. Petzer, Hans Salwender, Walter Fiedler, Heinz Kirchen, Detlef Haase, Stephan Kremers, Matthias Theobald, Axel C. MatzdorffArnold Ganser, Hartmut Döhner, Richard F. Schlenk

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19 Scopus citations

Abstract

Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m² intravenously on day 1), all-trans retinoic acid (45 mg/m² orally on days 4- 6 and 15 mg/m² orally on days 7-28), high-dose cytarabine (3 g/m²/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m² intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy.

Original languageEnglish
Pages (from-to)839-845
Number of pages7
JournalHaematologica
Volume101
Issue number7
DOIs
StatePublished - 2016

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