Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation

prognostic factors and impact of initial therapy of relapse

Andrew B.M. Lim, Cameron Curley, Chun Y. Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne M. Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer & 2 others Glen Kennedy, David Ritchie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background/Aims: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. Methods: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. Results: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3–4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1–2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). Conclusion: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3–4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.

Original languageEnglish
Pages (from-to)276-285
Number of pages10
JournalInternal Medicine Journal
Volume48
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018
Externally publishedYes

Keywords

  • acute myeloid leukaemia
  • allogeneic transplantation
  • relapse

Cite this

Lim, Andrew B.M. ; Curley, Cameron ; Fong, Chun Y. ; Bilmon, Ian ; Beligaswatte, Ashanka ; Purtill, Duncan ; Getta, Bartlomiej ; Johnston, Anne M. ; Armytage, Tasman ; Collins, Marnie ; Mason, Kate ; Fielding, Katherine ; Greenwood, Matthew ; Gibson, John ; Hertzberg, Mark ; Wright, Matthew ; Lewis, Ian ; Moore, John ; Curtis, David ; Szer, Jeff ; Kennedy, Glen ; Ritchie, David. / Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation : prognostic factors and impact of initial therapy of relapse. In: Internal Medicine Journal. 2018 ; Vol. 48, No. 3. pp. 276-285.
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title = "Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse",
abstract = "Background/Aims: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. Methods: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. Results: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3–4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1–2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2{\%}), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). Conclusion: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3–4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.",
keywords = "acute myeloid leukaemia, allogeneic transplantation, relapse",
author = "Lim, {Andrew B.M.} and Cameron Curley and Fong, {Chun Y.} and Ian Bilmon and Ashanka Beligaswatte and Duncan Purtill and Bartlomiej Getta and Johnston, {Anne M.} and Tasman Armytage and Marnie Collins and Kate Mason and Katherine Fielding and Matthew Greenwood and John Gibson and Mark Hertzberg and Matthew Wright and Ian Lewis and John Moore and David Curtis and Jeff Szer and Glen Kennedy and David Ritchie",
year = "2018",
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doi = "10.1111/imj.13522",
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Lim, ABM, Curley, C, Fong, CY, Bilmon, I, Beligaswatte, A, Purtill, D, Getta, B, Johnston, AM, Armytage, T, Collins, M, Mason, K, Fielding, K, Greenwood, M, Gibson, J, Hertzberg, M, Wright, M, Lewis, I, Moore, J, Curtis, D, Szer, J, Kennedy, G & Ritchie, D 2018, 'Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse', Internal Medicine Journal, vol. 48, no. 3, pp. 276-285. https://doi.org/10.1111/imj.13522

Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation : prognostic factors and impact of initial therapy of relapse. / Lim, Andrew B.M.; Curley, Cameron; Fong, Chun Y.; Bilmon, Ian; Beligaswatte, Ashanka; Purtill, Duncan; Getta, Bartlomiej; Johnston, Anne M.; Armytage, Tasman; Collins, Marnie; Mason, Kate; Fielding, Katherine; Greenwood, Matthew; Gibson, John; Hertzberg, Mark; Wright, Matthew; Lewis, Ian; Moore, John; Curtis, David; Szer, Jeff; Kennedy, Glen; Ritchie, David.

In: Internal Medicine Journal, Vol. 48, No. 3, 01.03.2018, p. 276-285.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation

T2 - prognostic factors and impact of initial therapy of relapse

AU - Lim, Andrew B.M.

AU - Curley, Cameron

AU - Fong, Chun Y.

AU - Bilmon, Ian

AU - Beligaswatte, Ashanka

AU - Purtill, Duncan

AU - Getta, Bartlomiej

AU - Johnston, Anne M.

AU - Armytage, Tasman

AU - Collins, Marnie

AU - Mason, Kate

AU - Fielding, Katherine

AU - Greenwood, Matthew

AU - Gibson, John

AU - Hertzberg, Mark

AU - Wright, Matthew

AU - Lewis, Ian

AU - Moore, John

AU - Curtis, David

AU - Szer, Jeff

AU - Kennedy, Glen

AU - Ritchie, David

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Background/Aims: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. Methods: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. Results: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3–4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1–2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). Conclusion: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3–4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.

AB - Background/Aims: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. Methods: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. Results: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3–4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1–2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). Conclusion: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3–4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.

KW - acute myeloid leukaemia

KW - allogeneic transplantation

KW - relapse

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U2 - 10.1111/imj.13522

DO - 10.1111/imj.13522

M3 - Article

VL - 48

SP - 276

EP - 285

JO - Internal Medicine Journal

JF - Internal Medicine Journal

SN - 1444-0903

IS - 3

ER -