Skip to main content
Top
Published in: International Journal of Hematology 5/2013

01-05-2013 | Original Article

Impact of pre-transplant marrow blasts on survival of allogeneic stem cell transplantation in adult acute myeloid leukemia

Authors: Sung-Eun Lee, Jae-Ho Yoon, Seung-Hwan Shin, Seung-Ah Yahng, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Chang-Ki Min, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Chong-Won Park, Myungshin Kim, Jihyang Lim, Yonggoo Kim, Kyungja Han, Hee-Je Kim

Published in: International Journal of Hematology | Issue 5/2013

Login to get access

Abstract

The aim of this study was to evaluate the impact of marrow blasts at transplant in adult acute myeloid leukemia (AML) patients. We analyzed 478 patients who underwent allogeneic stem cell transplantation (SCT). All patients were divided into five subgroups according to the percentage of blasts: <2 % (n = 361), ≥2 to<3 % (n = 64), ≥3 to <5 % (n = 28), ≥5 to <12 % (n = 11), and ≥12 % (n = 4). After a median follow-up of 59.5 months (range 3.3–125.9 months) for survivors, patients with higher marrow blasts at transplant showed lower overall survival (OS) and disease-free survival (DFS). In multivariate analyses, OS and DFS did not show significant differences with blast counts up to 12 %, compared with blast counts of <2 %; by contrast, the presence of >12 % marrow blasts was associated with significantly poorer OS and DFS. In the separate multivariate analyses by cytogenetic risk group, the impact of >12 % marrow blast on survival outcomes was observed in all risk groups. Thus, pre-transplant bone marrow status is an important prognostic factor for AML patients. In addition, the higher relapse rate in patients with >12 % marrow blasts may provide insights into the tolerable blast cell burden that can be overcome by the graft-versus leukemia effect.
Appendix
Available only for authorised users
Literature
1.
go back to reference Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, 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.PubMedCrossRef Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, 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.PubMedCrossRef
2.
go back to reference Michallet M, Thomas X, Vernant JP, Kuentz M, Socie G, Esperou-Bourdeau H, et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant. 2000;26:1157–63.PubMedCrossRef Michallet M, Thomas X, Vernant JP, Kuentz M, Socie G, Esperou-Bourdeau H, et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant. 2000;26:1157–63.PubMedCrossRef
3.
go back to reference Biggs JC, Horowitz MM, Gale RP, Ash RC, Atkinson K, Helbig W, et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood. 1992;80:1090–3.PubMed Biggs JC, Horowitz MM, Gale RP, Ash RC, Atkinson K, Helbig W, et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood. 1992;80:1090–3.PubMed
4.
go back to reference Armand P, Kim HT, DeAngelo DJ, Ho VT, Cutler CS, Stone RM, et al. Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol blood marrow transplant. 2007;13:655–64.PubMedCrossRef Armand P, Kim HT, DeAngelo DJ, Ho VT, Cutler CS, Stone RM, et al. Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol blood marrow transplant. 2007;13:655–64.PubMedCrossRef
5.
go back to reference Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325–36.PubMedCrossRef Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325–36.PubMedCrossRef
6.
go back to reference Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest oncology group/Eastern cooperative oncology group study. Blood. 2000;96:4075–83.PubMed Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest oncology group/Eastern cooperative oncology group study. Blood. 2000;96:4075–83.PubMed
7.
go back to reference Greinix HT, Nachbaur D, Krieger O, Eibl M, Knobl P, Kalhs P, et al. Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry. Br J Haematol. 2002;117:914–23.PubMedCrossRef Greinix HT, Nachbaur D, Krieger O, Eibl M, Knobl P, Kalhs P, et al. Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry. Br J Haematol. 2002;117:914–23.PubMedCrossRef
8.
go back to reference Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109:3658–66.PubMedCrossRef Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109:3658–66.PubMedCrossRef
9.
go back to reference Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000;26:397–404.PubMedCrossRef Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000;26:397–404.PubMedCrossRef
10.
go back to reference Song KW, Lipton J. Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia? Bone Marrow Transplant. 2005;36:183–91.PubMedCrossRef Song KW, Lipton J. Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia? Bone Marrow Transplant. 2005;36:183–91.PubMedCrossRef
11.
go back to reference Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef
12.
go back to reference Wahlin A, Billstrom R, Bjor O, Ahlgren T, Hedenus M, Hoglund M, et al. Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study. Eur J Haematol. 2009;83:99–107.PubMedCrossRef Wahlin A, Billstrom R, Bjor O, Ahlgren T, Hedenus M, Hoglund M, et al. Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study. Eur J Haematol. 2009;83:99–107.PubMedCrossRef
13.
go back to reference Kim M, Kim J, Lim J, Kim Y, Han K, Kang CS. Use of an automated hematology analyzer and flow cytometry to assess bone marrow cellularity and differential cell count. Ann Clin Lab Sci. 2004;34:307–13.PubMed Kim M, Kim J, Lim J, Kim Y, Han K, Kang CS. Use of an automated hematology analyzer and flow cytometry to assess bone marrow cellularity and differential cell count. Ann Clin Lab Sci. 2004;34:307–13.PubMed
14.
go back to reference Lee S, Kim YJ, Min CK, Kim HJ, Eom KS, Kim DW, et al. The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2005;105:3449–57.PubMedCrossRef Lee S, Kim YJ, Min CK, Kim HJ, Eom KS, Kim DW, et al. The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2005;105:3449–57.PubMedCrossRef
15.
go back to reference Min CK, Kim SY, Lee MJ, Eom KS, Kim YJ, Kim HJ, et al. Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;38:149–56.PubMedCrossRef Min CK, Kim SY, Lee MJ, Eom KS, Kim YJ, Kim HJ, et al. Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;38:149–56.PubMedCrossRef
16.
go back to reference Kim HJ, Min WS, Eom KS, Cho BS, Kim SY, Bok JN, et al. Anti-leukaemic role of acute GvHD after unrelated haematopoietic stem cell transplantation in intermediate- to high-risk acute myelogenous leukaemia. Bone Marrow Transplant. 2007;40:1069–74.PubMedCrossRef Kim HJ, Min WS, Eom KS, Cho BS, Kim SY, Bok JN, et al. Anti-leukaemic role of acute GvHD after unrelated haematopoietic stem cell transplantation in intermediate- to high-risk acute myelogenous leukaemia. Bone Marrow Transplant. 2007;40:1069–74.PubMedCrossRef
17.
go back to reference Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:704–17.PubMedCrossRef Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:704–17.PubMedCrossRef
18.
go back to reference Cho BS, Lee SE, Song HH, Lee JH, Yahng SA, Eom KS, et al. Graft-versus-tumor effect according to type of graft-versus-host disease defined by National Institutes of Health Consensus Criteria and associated outcomes. Biol Blood Marrow Transplant. 2012;18:1136–43.PubMedCrossRef Cho BS, Lee SE, Song HH, Lee JH, Yahng SA, Eom KS, et al. Graft-versus-tumor effect according to type of graft-versus-host disease defined by National Institutes of Health Consensus Criteria and associated outcomes. Biol Blood Marrow Transplant. 2012;18:1136–43.PubMedCrossRef
19.
go back to reference Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, 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, Appelbaum FR, Buchner T, Burnett AK, 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
20.
go back to reference Oyekunle AA, Kroger N, Zabelina T, Ayuk F, Schieder H, Renges H, et al. Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplant. 2006;37:45–50.PubMed Oyekunle AA, Kroger N, Zabelina T, Ayuk F, Schieder H, Renges H, et al. Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplant. 2006;37:45–50.PubMed
21.
go back to reference Kebriaei P, Kline J, Stock W, Kasza K, Le Beau MM, Larson RA, et al. Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant. 2005;35:965–70.PubMedCrossRef Kebriaei P, Kline J, Stock W, Kasza K, Le Beau MM, Larson RA, et al. Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant. 2005;35:965–70.PubMedCrossRef
22.
go back to reference Kim DH, Sohn SK, Kim JG, Lee NY, Sung WJ, Baek JH, et al. Parameters for predicting allogeneic PBSCT outcome of acute myeloid leukemia: cytogenetics at presentation versus disease status at transplantation. Ann Hematol. 2005;84:25–32.PubMedCrossRef Kim DH, Sohn SK, Kim JG, Lee NY, Sung WJ, Baek JH, et al. Parameters for predicting allogeneic PBSCT outcome of acute myeloid leukemia: cytogenetics at presentation versus disease status at transplantation. Ann Hematol. 2005;84:25–32.PubMedCrossRef
23.
go back to reference Ferrara F, Palmieri S, Mele G. Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia. Haematologica. 2004;89:998–1008.PubMed Ferrara F, Palmieri S, Mele G. Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia. Haematologica. 2004;89:998–1008.PubMed
24.
go back to reference Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–62.PubMed Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–62.PubMed
25.
go back to reference Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147:614–33.PubMedCrossRef Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147:614–33.PubMedCrossRef
26.
go back to reference Ringden O, Pavletic SZ, Anasetti C, Barrett AJ, Wang T, Wang D, et al. The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. Blood. 2009;113:3110–8.PubMedCrossRef Ringden O, Pavletic SZ, Anasetti C, Barrett AJ, Wang T, Wang D, et al. The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. Blood. 2009;113:3110–8.PubMedCrossRef
27.
go back to reference Ringden O, Labopin M, Gluckman E, Reiffers J, Vernant JP, Jouet JP, et al. Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute leukemia working party of the European group for blood and marrow transplantation. Bone Marrow Transplant. 1996;18:921–9.PubMed Ringden O, Labopin M, Gluckman E, Reiffers J, Vernant JP, Jouet JP, et al. Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute leukemia working party of the European group for blood and marrow transplantation. Bone Marrow Transplant. 1996;18:921–9.PubMed
Metadata
Title
Impact of pre-transplant marrow blasts on survival of allogeneic stem cell transplantation in adult acute myeloid leukemia
Authors
Sung-Eun Lee
Jae-Ho Yoon
Seung-Hwan Shin
Seung-Ah Yahng
Byung-Sik Cho
Ki-Seong Eom
Yoo-Jin Kim
Chang-Ki Min
Seok Lee
Seok-Goo Cho
Dong-Wook Kim
Jong-Wook Lee
Woo-Sung Min
Chong-Won Park
Myungshin Kim
Jihyang Lim
Yonggoo Kim
Kyungja Han
Hee-Je Kim
Publication date
01-05-2013
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2013
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-013-1312-1

Other articles of this Issue 5/2013

International Journal of Hematology 5/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine