Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Graft-Versus-Host Disease | Research article

Early transplantation-related mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia

Authors: Seom Gim Kong, Seri Jeong, Sangjin Lee, Jee-Yeong Jeong, Da Jung Kim, Ho Sup Lee

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Background

Transplantation-related mortality (TRM) is a major obstacle in allogeneic hematopoietic cell transplantation (allo-HCT). Approximately 60–80% of TRM occurs early, within 100 days of transplantation.

Methods

This was a nationwide population cohort study involving 5395 patients with acute leukemia who underwent allo-HCT between 2003 and 2015. Patient data were collected from the Korean National Health Insurance Service database. We investigated the cumulative incidence rates (CIRs) of early TRM at 50 and 100 days.

Results

The CIRs of early TRM at 50 and 100 days were 2.9 and 8.3%, respectively. There was no decrease in the CIRs of early TRM over time. The early mortality was significantly higher in patients with more than 9 months between the diagnosis and transplantation (CIRs of TRM at 50, 100 days; 6.0, 13.2%), previous transplantations (CIRs of TRM at 50, 100 days; 9.4, 17.2%), and cord blood transplantation (CIRs of TRM at 50, 100 days; 6.1, 8.3%). The early TRM was significantly lower in patients who received iron chelation before transplantation (CIRs of TRM at 50, 100 days; 0.3, 1.8%).

Conclusions

In conclusion, the overall CIR of early TRM was less than 10%. The predictable factors for early TRM included age, time from diagnosis to transplantation, the number of prior transplantations, the graft source, and previous iron chelation therapy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hahn T, McCarthy PL Jr, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31:2437–49.CrossRef Hahn T, McCarthy PL Jr, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31:2437–49.CrossRef
2.
go back to reference Styczyński J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020;55:126–36.CrossRef Styczyński J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020;55:126–36.CrossRef
3.
go back to reference Miano M, Labopin M, Hartmann O, Angelucci E, Cornish J, Gluckman E, et al. Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European group for blood and marrow transplantation. Bone Marrow Transplant. 2007;39:89–99.CrossRef Miano M, Labopin M, Hartmann O, Angelucci E, Cornish J, Gluckman E, et al. Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European group for blood and marrow transplantation. Bone Marrow Transplant. 2007;39:89–99.CrossRef
4.
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.CrossRef 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.CrossRef
5.
go back to reference Cornelissen JJ, Carston M, Kollman C, King R, Dekker AW, Löwenberg B, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001;97:1572–7.CrossRef Cornelissen JJ, Carston M, Kollman C, King R, Dekker AW, Löwenberg B, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001;97:1572–7.CrossRef
6.
go back to reference Bunin NJ, Davies SM, Aplenc R, Camitta BM, DeSantes KB, Goyal RK, et al. Unrelated donor bone marrow transplantation for children with acute myeloid leukemia beyond first remission or refractory to chemotherapy. J Clin Oncol. 2008;26:4326–32.CrossRef Bunin NJ, Davies SM, Aplenc R, Camitta BM, DeSantes KB, Goyal RK, et al. Unrelated donor bone marrow transplantation for children with acute myeloid leukemia beyond first remission or refractory to chemotherapy. J Clin Oncol. 2008;26:4326–32.CrossRef
7.
go back to reference Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S, et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004;89:1238–47.PubMed Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S, et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004;89:1238–47.PubMed
8.
go back to reference Iida M, Kodera Y, Dodds A, Ho AYL, Nivison-Smith I, Akter MR, et al. Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015. Bone Marrow Transplant. 2019;54:1973–86.CrossRef Iida M, Kodera Y, Dodds A, Ho AYL, Nivison-Smith I, Akter MR, et al. Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015. Bone Marrow Transplant. 2019;54:1973–86.CrossRef
9.
go back to reference Remberger M, Ackefors M, Berglund S, Blennow O, Dahllöf G, Dlugosz A, et al. Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant. 2011;17:1688–97.CrossRef Remberger M, Ackefors M, Berglund S, Blennow O, Dahllöf G, Dlugosz A, et al. Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant. 2011;17:1688–97.CrossRef
10.
go back to reference Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.CrossRef Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.CrossRef
11.
go back to reference Horan JT, Logan BR, Agovi-Johnson M-A, Lazarus HM, Bacigalupo AA, Ballen KK, et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol. 2011;29:805–13.CrossRef Horan JT, Logan BR, Agovi-Johnson M-A, Lazarus HM, Bacigalupo AA, Ballen KK, et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol. 2011;29:805–13.CrossRef
12.
go back to reference Woolfrey AE, Anasetti C, Storer B, Doney K, Milner LA, Sievers EL, et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood. 2002;99:2002–8.CrossRef Woolfrey AE, Anasetti C, Storer B, Doney K, Milner LA, Sievers EL, et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood. 2002;99:2002–8.CrossRef
13.
go back to reference Bunin N, Carston M, Wall D, Adams R, Casper J, Kamani N, et al. Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood. 2002;99:3151–7.CrossRef Bunin N, Carston M, Wall D, Adams R, Casper J, Kamani N, et al. Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood. 2002;99:3151–7.CrossRef
14.
go back to reference Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110:4576–83.CrossRef Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110:4576–83.CrossRef
15.
go back to reference Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME, et al. Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood. 2007;110:1379–87.CrossRef Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME, et al. Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood. 2007;110:1379–87.CrossRef
16.
go back to reference Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001;344:1815–22.CrossRef Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001;344:1815–22.CrossRef
17.
go back to reference Moukalled NM, Kharfan-Dabaja MA. What is the role of a second allogeneic hematopoietic cell transplant in relapsed acute myeloid leukemia? Bone Marrow Transplant. 2020;55:325–31.CrossRef Moukalled NM, Kharfan-Dabaja MA. What is the role of a second allogeneic hematopoietic cell transplant in relapsed acute myeloid leukemia? Bone Marrow Transplant. 2020;55:325–31.CrossRef
18.
go back to reference Orti G, Sanz J, Bermudez A, Caballero D, Martinez C, Sierra J, et al. Outcome of second allogeneic hematopoietic cell transplantation after relapse of myeloid malignancies following allogeneic hematopoietic cell transplantation: a retrospective cohort on behalf of the Grupo Español de Trasplante Hematopoyetico. Biol Blood Marrow Transplant. 2016;22:584–8.CrossRef Orti G, Sanz J, Bermudez A, Caballero D, Martinez C, Sierra J, et al. Outcome of second allogeneic hematopoietic cell transplantation after relapse of myeloid malignancies following allogeneic hematopoietic cell transplantation: a retrospective cohort on behalf of the Grupo Español de Trasplante Hematopoyetico. Biol Blood Marrow Transplant. 2016;22:584–8.CrossRef
19.
go back to reference Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322:417–21.CrossRef Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322:417–21.CrossRef
20.
go back to reference Altès A, Remacha AF, Sureda A, Martino R, Briones J, Canals C, et al. Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation. Bone Marrow Transplant. 2002;29:987–9.CrossRef Altès A, Remacha AF, Sureda A, Martino R, Briones J, Canals C, et al. Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation. Bone Marrow Transplant. 2002;29:987–9.CrossRef
21.
go back to reference Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109:4586–8.CrossRef Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109:4586–8.CrossRef
22.
go back to reference Kim YR, Kim JS, Cheong JW, Song JW, Min YH. Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies. Acta Haematol. 2008;120:182–9.CrossRef Kim YR, Kim JS, Cheong JW, Song JW, Min YH. Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies. Acta Haematol. 2008;120:182–9.CrossRef
23.
go back to reference Pullarkat V, Blanchard S, Tegtmeier B, Dagis A, Patane K, Ito J, et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2008;42:799–805.CrossRef Pullarkat V, Blanchard S, Tegtmeier B, Dagis A, Patane K, Ito J, et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2008;42:799–805.CrossRef
24.
go back to reference Kataoka K, Nannya Y, Hangaishi A, Imai Y, Chiba S, Takahashi T, et al. Influence of pretransplantation serum ferritin on nonrelapse mortality after myeloablative and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:195–204.CrossRef Kataoka K, Nannya Y, Hangaishi A, Imai Y, Chiba S, Takahashi T, et al. Influence of pretransplantation serum ferritin on nonrelapse mortality after myeloablative and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:195–204.CrossRef
25.
go back to reference Wang Z, Jia M, Zhao H, Cheng Y, Luo Z, Chen Y, et al. Prognostic impact of pretransplantation hyperferritinemia in adults undergoing allogeneic hematopoietic SCT: a meta-analysis. Bone Marrow Transplant. 2014;49:1339–40.CrossRef Wang Z, Jia M, Zhao H, Cheng Y, Luo Z, Chen Y, et al. Prognostic impact of pretransplantation hyperferritinemia in adults undergoing allogeneic hematopoietic SCT: a meta-analysis. Bone Marrow Transplant. 2014;49:1339–40.CrossRef
26.
go back to reference Maradei SC, Maiolino A, de Azevedo AM, Colares M, Bouzas LF, Nucci M. Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood. 2009;114:1270–5.CrossRef Maradei SC, Maiolino A, de Azevedo AM, Colares M, Bouzas LF, Nucci M. Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood. 2009;114:1270–5.CrossRef
27.
go back to reference Sivgin S, Baldane S, Akyol G, Keklik M, Kaynar L, Kurnaz F, et al. The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload. Transfus Apher Sci. 2013;49:295–301.CrossRef Sivgin S, Baldane S, Akyol G, Keklik M, Kaynar L, Kurnaz F, et al. The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload. Transfus Apher Sci. 2013;49:295–301.CrossRef
28.
go back to reference Leitch HA, Parmar A, Wells RA, Chodirker L, Zhu N, Nevill TJ, et al. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis. Br J Haematol. 2017;179:83–97.CrossRef Leitch HA, Parmar A, Wells RA, Chodirker L, Zhu N, Nevill TJ, et al. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis. Br J Haematol. 2017;179:83–97.CrossRef
29.
go back to reference Sahlstedt L, Ebeling F, von Bonsdorff L, Parkkinen J, Ruutu T. Non-transferrin-bound iron during allogeneic stem cell transplantation. Br J Haematol. 2001;113:836–8.CrossRef Sahlstedt L, Ebeling F, von Bonsdorff L, Parkkinen J, Ruutu T. Non-transferrin-bound iron during allogeneic stem cell transplantation. Br J Haematol. 2001;113:836–8.CrossRef
30.
go back to reference Armand P, Sainvil MM, Kim HT, Rhodes J, Cutler C, Ho VT, et al. Pre-transplantation iron chelation in patients with MDS or acute leukemia and iron overload undergoing myeloablative allo-SCT. Bone Marrow Transplant. 2013;48:146–7.CrossRef Armand P, Sainvil MM, Kim HT, Rhodes J, Cutler C, Ho VT, et al. Pre-transplantation iron chelation in patients with MDS or acute leukemia and iron overload undergoing myeloablative allo-SCT. Bone Marrow Transplant. 2013;48:146–7.CrossRef
31.
go back to reference Atilla E, Toprak SK, Demirer T. Current review of iron overload and related complications in hematopoietic stem cell transplantation. Turk J Haematol. 2017;34:1–9.CrossRef Atilla E, Toprak SK, Demirer T. Current review of iron overload and related complications in hematopoietic stem cell transplantation. Turk J Haematol. 2017;34:1–9.CrossRef
Metadata
Title
Early transplantation-related mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia
Authors
Seom Gim Kong
Seri Jeong
Sangjin Lee
Jee-Yeong Jeong
Da Jung Kim
Ho Sup Lee
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07897-3

Other articles of this Issue 1/2021

BMC Cancer 1/2021 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