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Erschienen in: Medical Oncology 6/2014

01.06.2014 | Original Paper

High-dose idarubicin plus busulfan as conditioning regimen to autologous stem cell transplantation: Promising post-remission therapy for acute myeloid leukemia in first complete remission?

verfasst von: Ming Hong, Kou-Rong Miao, Run Zhang, Hua Lu, Peng Liu, Wei Xu, Li-Juan Chen, Su-Jiang Zhang, Han-Xin Wu, Hong-Xia Qiu, Jian-Yong Li, Si-Xuan Qian

Erschienen in: Medical Oncology | Ausgabe 6/2014

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Abstract

The optimal post-remission therapy (PRT) for acute myeloid leukemia (AML) remains uncertain. We reported 32 AML patients in first complete remission (CR1) undergoing autologous hematopoietic stem cell transplantation (ASCT) with a characteristic conditioning regimen, termed I-Bu, based on high-dose idarubicin plus busulfan, which considerably strengthened antileukemic activity. Most patients were in better or intermediate-risk group except that cytogenetic or molecular risk information was missing for 18.7 % of the patients. Unpurged peripheral blood stem cells were used in all the cases. The adverse effects were mild and reversible. Only one case of transplant-related mortality was observed. All the patients in this study acquired hematopoietic reconstitution after ASCT. After a median follow-up of 30 (6–119) months, 24 patients (75.0 %) were alive in which 20 (62.5 %) patients were in continuous CR. There were 11 (34.4 %) patients who relapsed after HSCT. Cumulative relapse probability was about 40 % after 24 months. Median OS and DFS have not been reached. Patients in the better and intermediate-risk group had different clinical outcomes, but the differences were not statistically significant. ASCT with I-Bu regimen is possibly promising PRT for better and intermediate-risk AML patients in CR1.
Literatur
1.
Zurück zum Zitat O’donnell MR, Abboud CN, Altman J, et al. Acute myeloid leukemia. J Natl Compr Canc Netw. 2012;10:984–1021.PubMed O’donnell MR, Abboud CN, Altman J, et al. Acute myeloid leukemia. J Natl Compr Canc Netw. 2012;10:984–1021.PubMed
2.
Zurück zum Zitat Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 2011;117:2307–18.PubMedCrossRef Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 2011;117:2307–18.PubMedCrossRef
3.
Zurück zum Zitat Keating A, Dasilva G, Perez WS, et al. Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Haematologica. 2013;98:185–92.PubMedCentralPubMedCrossRef Keating A, Dasilva G, Perez WS, et al. Autologous blood cell transplantation versus HLA-identical sibling transplantation for acute myeloid leukemia in first complete remission: a registry study from the Center for International Blood and Marrow Transplantation Research. Haematologica. 2013;98:185–92.PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Burnett AK, Goldstone AH, Stevens RM, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children’s Leukaemia Working Parties. Lancet. 1998;351:700–8.PubMedCrossRef Burnett AK, Goldstone AH, Stevens RM, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children’s Leukaemia Working Parties. Lancet. 1998;351:700–8.PubMedCrossRef
5.
Zurück zum Zitat Mollee P, Gupta V, Song K, et al. Long-term outcome after intensive therapy with etoposide, melphalan, total body irradiation and autotransplant for acute myeloid leukemia. Bone Marrow Transplant. 2004;33:1201–8.PubMedCrossRef Mollee P, Gupta V, Song K, et al. Long-term outcome after intensive therapy with etoposide, melphalan, total body irradiation and autotransplant for acute myeloid leukemia. Bone Marrow Transplant. 2004;33:1201–8.PubMedCrossRef
6.
Zurück zum Zitat Suciu S, Mandelli F, De Witte T, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102:1232–40.PubMedCrossRef Suciu S, Mandelli F, De Witte T, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102:1232–40.PubMedCrossRef
7.
Zurück zum Zitat Guieze R, Cornillet-Lefebvre P, Lioure B, et al. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study. Am J Hematol. 2012;87:1052–6.PubMedCrossRef Guieze R, Cornillet-Lefebvre P, Lioure B, et al. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study. Am J Hematol. 2012;87:1052–6.PubMedCrossRef
8.
Zurück zum Zitat Majhail NS, Bajorunaite R, Lazarus HM, et al. High probability of long-term survival in 2-year survivors of autologous hematopoietic cell transplantation for AML in first or second CR. Bone Marrow Transplant. 2011;46:385–92.PubMedCentralPubMedCrossRef Majhail NS, Bajorunaite R, Lazarus HM, et al. High probability of long-term survival in 2-year survivors of autologous hematopoietic cell transplantation for AML in first or second CR. Bone Marrow Transplant. 2011;46:385–92.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Vellenga E, Van Putten W, Ossenkoppele GJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118:6037–42.PubMedCrossRef Vellenga E, Van Putten W, Ossenkoppele GJ, et al. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011;118:6037–42.PubMedCrossRef
10.
Zurück zum Zitat Wang J, Ouyang J, Zhou R, et al. Autologous hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission: a meta-analysis of randomized trials. Acta Haematol. 2010;124:61–71.PubMedCrossRef Wang J, Ouyang J, Zhou R, et al. Autologous hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission: a meta-analysis of randomized trials. Acta Haematol. 2010;124:61–71.PubMedCrossRef
11.
Zurück zum Zitat Breems DA, Boogaerts MA, Dekker AW, et al. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005;128:59–65.PubMedCrossRef Breems DA, Boogaerts MA, Dekker AW, et al. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005;128:59–65.PubMedCrossRef
12.
Zurück zum Zitat Gorin NC, Labopin M, Frassoni F, et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8;21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26:3183–8.PubMedCrossRef Gorin NC, Labopin M, Frassoni F, et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8;21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26:3183–8.PubMedCrossRef
13.
Zurück zum Zitat Linker CA. Autologous stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplant. 2003;31:731–8.PubMedCrossRef Linker CA. Autologous stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplant. 2003;31:731–8.PubMedCrossRef
14.
Zurück zum Zitat Linker CA, Ries CA, Damon LE, et al. Autologous stem cell transplantation for acute myeloid leukemia in first remission. Biol Blood Marrow Transplant. 2000;6:50–7.PubMedCrossRef Linker CA, Ries CA, Damon LE, et al. Autologous stem cell transplantation for acute myeloid leukemia in first remission. Biol Blood Marrow Transplant. 2000;6:50–7.PubMedCrossRef
15.
Zurück zum Zitat Buccisano F, Maurillo L, Spagnoli A, et al. Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia. Blood. 2010;116:2295–303.PubMedCrossRef Buccisano F, Maurillo L, Spagnoli A, et al. Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia. Blood. 2010;116:2295–303.PubMedCrossRef
16.
Zurück zum Zitat Ferrara F, Annunziata M, Schiavone EM, et al. High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study. Hematol J. 2001;2:214–9.PubMedCrossRef Ferrara F, Annunziata M, Schiavone EM, et al. High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study. Hematol J. 2001;2:214–9.PubMedCrossRef
17.
Zurück zum Zitat Ferrara F, Izzo T, Criscuolo C, et al. Favorable outcome in patients with acute myelogenous leukemia with the nucleophosmin gene mutation autografted after conditioning with high-dose continuous infusion of idarubicin and busulfan. Biol Blood Marrow Transplant. 2010;16:1018–24.PubMedCrossRef Ferrara F, Izzo T, Criscuolo C, et al. Favorable outcome in patients with acute myelogenous leukemia with the nucleophosmin gene mutation autografted after conditioning with high-dose continuous infusion of idarubicin and busulfan. Biol Blood Marrow Transplant. 2010;16:1018–24.PubMedCrossRef
18.
Zurück zum Zitat Ferrara F, Palmieri S, Annunziata M, et al. Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2004;34:573–6.PubMedCrossRef Ferrara F, Palmieri S, Annunziata M, et al. Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2004;34:573–6.PubMedCrossRef
19.
Zurück zum Zitat Ferrara F, Palmieri S, Pedata M, et al. Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan. Hematol Oncol. 2009;27:40–5.PubMedCrossRef Ferrara F, Palmieri S, Pedata M, et al. Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan. Hematol Oncol. 2009;27:40–5.PubMedCrossRef
20.
Zurück zum Zitat Yin CC, Medeiros LJ, Bueso-Ramos CE. Recent advances in the diagnosis and classification of myeloid neoplasms–comments on the 2008 WHO classification. Int J Lab Hematol. 2010;32:461–76.PubMedCrossRef Yin CC, Medeiros LJ, Bueso-Ramos CE. Recent advances in the diagnosis and classification of myeloid neoplasms–comments on the 2008 WHO classification. Int J Lab Hematol. 2010;32:461–76.PubMedCrossRef
21.
Zurück zum Zitat Berman E, Heller G, Santorsa J, et al. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991;77:1666–74.PubMed Berman E, Heller G, Santorsa J, et al. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991;77:1666–74.PubMed
22.
Zurück zum Zitat Qian SX, Li JY, Tian T, et al. Effect of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on the outcome of elderly patients with acute myeloid leukemia. Leuk Res. 2007;31:1383–8.PubMedCrossRef Qian SX, Li JY, Tian T, et al. Effect of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on the outcome of elderly patients with acute myeloid leukemia. Leuk Res. 2007;31:1383–8.PubMedCrossRef
23.
Zurück zum Zitat Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29:487–94.PubMedCrossRef Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29:487–94.PubMedCrossRef
24.
Zurück zum Zitat Buchner T, Berdel WE, Schoch C, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol. 2006;24:2480–9.PubMedCrossRef Buchner T, Berdel WE, Schoch C, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol. 2006;24:2480–9.PubMedCrossRef
25.
Zurück zum Zitat Jung AS, Holman PR, Castro JE, et al. Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:1306–13.PubMedCrossRef Jung AS, Holman PR, Castro JE, et al. Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:1306–13.PubMedCrossRef
26.
Zurück zum Zitat Singh H, Werner LL, Asali S, et al. Comparison of autologous stem cell transplantation versus consolidation chemotherapy for patients with cytogenetically normal acute myeloid leukemia (CN-AML) and FLT3ITD. Am J Hematol. 2011;86:625–7.PubMedCentralPubMedCrossRef Singh H, Werner LL, Asali S, et al. Comparison of autologous stem cell transplantation versus consolidation chemotherapy for patients with cytogenetically normal acute myeloid leukemia (CN-AML) and FLT3ITD. Am J Hematol. 2011;86:625–7.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Tallman MS, Perez WS, Lazarus HM, et al. Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 2006;12:204–16.PubMedCrossRef Tallman MS, Perez WS, Lazarus HM, et al. Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 2006;12:204–16.PubMedCrossRef
28.
Zurück zum Zitat Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995;332:217–23.PubMedCrossRef Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995;332:217–23.PubMedCrossRef
29.
Zurück zum Zitat Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.PubMedCrossRef Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.PubMedCrossRef
30.
Zurück zum Zitat Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301:2349–61.PubMedCentralPubMedCrossRef Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301:2349–61.PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Pfirrmann M, Ehninger G, Thiede C, et al. Prediction of post-remission survival in acute myeloid leukaemia: a post hoc analysis of the AML96 trial. Lancet Oncol. 2012;13:207–14.PubMedCrossRef Pfirrmann M, Ehninger G, Thiede C, et al. Prediction of post-remission survival in acute myeloid leukaemia: a post hoc analysis of the AML96 trial. Lancet Oncol. 2012;13:207–14.PubMedCrossRef
Metadaten
Titel
High-dose idarubicin plus busulfan as conditioning regimen to autologous stem cell transplantation: Promising post-remission therapy for acute myeloid leukemia in first complete remission?
verfasst von
Ming Hong
Kou-Rong Miao
Run Zhang
Hua Lu
Peng Liu
Wei Xu
Li-Juan Chen
Su-Jiang Zhang
Han-Xin Wu
Hong-Xia Qiu
Jian-Yong Li
Si-Xuan Qian
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 6/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0980-x

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