Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease

Francesca A M Kinsella; Charlotte F Inman; Amy Gudger; Yuen T Chan; Duncan J Murray; Jianmin Zuo; Graham McIlroy; Sandeep Nagra; Jane Nunnick; Kathy Holder; Kerry Wall; Mike Griffiths; Charles Craddock; Emmanouil Nikolousis; Paul Moss; Ram Malladi

doi:10.1016/j.leukres.2019.106173

Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease

Francesca A M Kinsella, Charlotte F Inman, Amy Gudger, Yuen T Chan, Duncan J Murray, Jianmin Zuo, Graham McIlroy, Sandeep Nagra, Jane Nunnick, Kathy Holder, Kerry Wall, Mike Griffiths, Charles Craddock, Emmanouil Nikolousis, Paul Moss, Ram Malladi

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Abstract

BACKGROUND: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.

METHODS: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells.

RESULTS: In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma.

CONCLUSION: The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management.

Original language	English
Article number	106173
Number of pages	7
Journal	Leukemia Research
Volume	83
Early online date	18 Jun 2019
DOIs	https://doi.org/10.1016/j.leukres.2019.106173 https://doi.org/10.1016/j.leukres.2019.106173
Publication status	Published - 1 Aug 2019

Bibliographical note

Keywords

Chimerism
AML
Allogeneic-HSCT
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Kinsella_et_al_Very_early_lineage_specific_chimerism_after_reduced_intensity_stem_cell_transplantation_Leukemia_Research_2019
Checked for eligibility: 20/09/2019
Accepted author manuscript, 277 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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Kinsella, F. A. M., Inman, C. F., Gudger, A., Chan, Y. T., Murray, D. J., Zuo, J., McIlroy, G., Nagra, S., Nunnick, J., Holder, K., Wall, K., Griffiths, M., Craddock, C., Nikolousis, E., Moss, P., & Malladi, R. (2019). Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease. Leukemia Research, 83, Article 106173. https://doi.org/10.1016/j.leukres.2019.106173, https://doi.org/10.1016/j.leukres.2019.106173

@article{69e889edffb943ef81814cb8bb8cf92f,

title = "Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease",

abstract = "BACKGROUND: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.METHODS: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells.RESULTS: In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma.CONCLUSION: The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management.",

keywords = "Chimerism, AML, Allogeneic-HSCT, Relapse",

author = "Kinsella, {Francesca A M} and Inman, {Charlotte F} and Amy Gudger and Chan, {Yuen T} and Murray, {Duncan J} and Jianmin Zuo and Graham McIlroy and Sandeep Nagra and Jane Nunnick and Kathy Holder and Kerry Wall and Mike Griffiths and Charles Craddock and Emmanouil Nikolousis and Paul Moss and Ram Malladi",

note = "Copyright {\textcopyright} 2019. Published by Elsevier Ltd.",

year = "2019",

month = aug,

day = "1",

doi = "10.1016/j.leukres.2019.106173",

language = "English",

volume = "83",

journal = "Leukemia Research",

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Kinsella, FAM, Inman, CF, Gudger, A, Chan, YT, Murray, DJ, Zuo, J, McIlroy, G, Nagra, S, Nunnick, J, Holder, K, Wall, K, Griffiths, M, Craddock, C, Nikolousis, E, Moss, P & Malladi, R 2019, 'Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease', Leukemia Research, vol. 83, 106173. https://doi.org/10.1016/j.leukres.2019.106173, https://doi.org/10.1016/j.leukres.2019.106173

TY - JOUR

T1 - Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease

AU - Kinsella, Francesca A M

AU - Inman, Charlotte F

AU - Gudger, Amy

AU - Chan, Yuen T

AU - Murray, Duncan J

AU - Zuo, Jianmin

AU - McIlroy, Graham

AU - Nagra, Sandeep

AU - Nunnick, Jane

AU - Holder, Kathy

AU - Wall, Kerry

AU - Griffiths, Mike

AU - Craddock, Charles

AU - Nikolousis, Emmanouil

AU - Moss, Paul

AU - Malladi, Ram

PY - 2019/8/1

Y1 - 2019/8/1

N2 - BACKGROUND: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.METHODS: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells.RESULTS: In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma.CONCLUSION: The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management.

AB - BACKGROUND: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.METHODS: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells.RESULTS: In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma.CONCLUSION: The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management.

KW - Chimerism

KW - AML

KW - Allogeneic-HSCT

KW - Relapse

UR - http://dx.doi.org/10.1016/j.leukres.2019.106173

U2 - 10.1016/j.leukres.2019.106173

DO - 10.1016/j.leukres.2019.106173

M3 - Article

C2 - 31276965

SN - 0145-2126

VL - 83

JO - Leukemia Research

JF - Leukemia Research

M1 - 106173

ER -

Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease

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