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
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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. / Hütter-Krönke, Marie-Luise; Benner, Axel; Döhner, Konstanze; Krauter, Jürgen; Weber, Daniela; Moessner, Margit; Köhne, Claus-Henning; Horst, Heinz A; Schmidt-Wolf, Ingo G H; Rummel, Mathias; Götze, Katharina; Koller, Elisabeth; Petzer, Andreas L; Salwender, Hans; Fiedler, Walter; Kirchen, Heinz; Haase, Detlef; Kremers, Stephan; Theobald, Matthias; Matzdorff, Axel C; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F.
In: HAEMATOLOGICA, Vol. 101, No. 7, 07.2016, p. 839-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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
AU - Hütter-Krönke, Marie-Luise
AU - Benner, Axel
AU - Döhner, Konstanze
AU - Krauter, Jürgen
AU - Weber, Daniela
AU - Moessner, Margit
AU - Köhne, Claus-Henning
AU - Horst, Heinz A
AU - Schmidt-Wolf, Ingo G H
AU - Rummel, Mathias
AU - Götze, Katharina
AU - Koller, Elisabeth
AU - Petzer, Andreas L
AU - Salwender, Hans
AU - Fiedler, Walter
AU - Kirchen, Heinz
AU - Haase, Detlef
AU - Kremers, Stephan
AU - Theobald, Matthias
AU - Matzdorff, Axel C
AU - Ganser, Arnold
AU - Döhner, Hartmut
AU - Schlenk, Richard F
N1 - Copyright © 2016, Ferrata Storti Foundation.
PY - 2016/7
Y1 - 2016/7
N2 - Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3mg/m2; intravenously on day 1), all-trans retinoic acid (45 mg/m2; per 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 to 60 years refractory to one cycle of induction therapy. Primary endpoint of the study was response to therapy; secondary endpoints 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. (ClinicalTrials.gov,NCT00143975).
AB - Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3mg/m2; intravenously on day 1), all-trans retinoic acid (45 mg/m2; per 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 to 60 years refractory to one cycle of induction therapy. Primary endpoint of the study was response to therapy; secondary endpoints 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. (ClinicalTrials.gov,NCT00143975).
U2 - 10.3324/haematol.2015.141622
DO - 10.3324/haematol.2015.141622
M3 - SCORING: Journal article
C2 - 27036160
VL - 101
SP - 839
EP - 845
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 7
ER -