Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis

Abhinav Deol; Salyka Sengsayadeth; Kwang Woo Ahn; Hai Lin Wang; Mahmoud Aljurf; Joseph Harry Antin; Minoo Battiwalla; Martin Bornhauser; Jean Yves Cahn; Bruce Camitta; Yi Bin Chen; Corey S. Cutler; Robert Peter Gale; Siddhartha Ganguly; Mehdi Hamadani; Yoshihiro Inamoto; Madan Jagasia; Rammurti Kamble; John Koreth; Hillard M. Lazarus; Jane Liesveld; Mark R. Litzow; David I. Marks; Taiga Nishihori; Richard F. Olsson; Ran Reshef; Jacob M. Rowe; Ayman A. Saad; Mitchell Sabloff; Harry C. Schouten; Thomas C. Shea; Robert J. Soiffer; Geoffrey L. Uy; Edmond K. Waller; Peter H. Wiernik; Baldeep Wirk; Ann E. Woolfrey; Donald Bunjes; Steven Devine; Marcos de Lima; Brenda M. Sandmaier; Dan Weisdorf; Hanna Jean Khoury; Wael Saber

doi:10.1002/cncr.30140

Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis

Abhinav Deol, Salyka Sengsayadeth, Kwang Woo Ahn, Hai Lin Wang, Mahmoud Aljurf, Joseph Harry Antin, Minoo Battiwalla, Martin Bornhauser, Jean Yves Cahn, Bruce Camitta, Yi Bin Chen, Corey S. Cutler, Robert Peter Gale, Siddhartha Ganguly, Mehdi Hamadani, Yoshihiro Inamoto, Madan Jagasia, Rammurti Kamble, John Koreth, Hillard M. LazarusJane Liesveld, Mark R. Litzow, David I. Marks, Taiga Nishihori, Richard F. Olsson, Ran Reshef, Jacob M. Rowe, Ayman A. Saad, Mitchell Sabloff, Harry C. Schouten, Thomas C. Shea, Robert J. Soiffer, Geoffrey L. Uy, Edmond K. Waller, Peter H. Wiernik, Baldeep Wirk, Ann E. Woolfrey, Donald Bunjes, Steven Devine, Marcos de Lima, Brenda M. Sandmaier, Dan Weisdorf, Hanna Jean Khoury, Wael Saber

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P5.04; relative risk, 1.60 [95% CI, 1.15-2.22]; P5.0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P5.20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.

Original language	English (US)
Pages (from-to)	3005-3014
Number of pages	10
Journal	Cancer
Volume	122
Issue number	19
DOIs	https://doi.org/10.1002/cncr.30140
State	Published - Oct 2016

Bibliographical note

Funding Information:
The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by a Public Health Service grant (cooperative agreement 5U24-CA076518) from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); by the NHLIB and the NCI (grant/cooperative agreement 5U10HL069294); by the Health Resources and Services Administration/Department of Health and Human Services (contract HHSH250201200016C; grants N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; by an anonymous donation to the Medical College of Wisconsin; and by grants from Alexion; Amgen, Inc (a corporate member); Be the Match Foundation; Bristol-Myers Squibb Oncology (a corporate member); Celgene Corporation (a corporate member); Chimerix, Inc (a corporate member); the Fred Hutchinson Cancer Research Center; Gamida Cell Ltd; Genentech, Inc; Genzyme Corporation; Gilead Sciences, Inc (a corporate member); Health Research, Inc; the Roswell Park Cancer Institute; HistoGenetics, Inc; Incyte Corporation; Jazz Pharmaceuticals, Inc (a corporate member); Jeff Gordon Children’s Foundation; The Leukemia and Lymphoma Society; The Medical College of Wisconsin; Merck and Company, Inc; Mesoblast; Millennium: The Takeda Oncology Company; Miltenyi Biotec, Inc (a corporate member); the National Marrow Donor Program; Neovii Biotech NA, Inc; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Health Care Solutions, Inc; Otsuka America Pharmaceutical, Inc; Otsuka Pharmaceutical Company, Ltd-Japan; Oxford Immunotec; Perkin Elmer, Inc; Pharmacyclics; Sanofi US (a corporate member); Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc (a corporate member); St Baldrick’s Foundation; Sunesis Pharmaceuticals, Inc (a corporate member); Swedish Orphan Biovitrum, Inc; Telomere Diagnostics, Inc; TerumoBCT; Therakos, Inc; the University of Minnesota; and Wellpoint, Inc (a corporate member).

Publisher Copyright:
© 2016 American Cancer Society.

Keywords

1 more
Acute myeloid leukemia
Allogeneic stem cell transplantation
FMS-like tyrosine kinase 3 (FLT3)

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10.1002/cncr.30140

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Deol, A., Sengsayadeth, S., Ahn, K. W., Wang, H. L., Aljurf, M., Antin, J. H., Battiwalla, M., Bornhauser, M., Cahn, J. Y., Camitta, B., Chen, Y. B., Cutler, C. S., Gale, R. P., Ganguly, S., Hamadani, M., Inamoto, Y., Jagasia, M., Kamble, R., Koreth, J., ... Saber, W. (2016). Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis. Cancer, 122(19), 3005-3014. https://doi.org/10.1002/cncr.30140

Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis. / Deol, Abhinav; Sengsayadeth, Salyka; Ahn, Kwang Woo et al.

In: Cancer, Vol. 122, No. 19, 10.2016, p. 3005-3014.

Research output: Contribution to journal › Article › peer-review

Deol, A, Sengsayadeth, S, Ahn, KW, Wang, HL, Aljurf, M, Antin, JH, Battiwalla, M, Bornhauser, M, Cahn, JY, Camitta, B, Chen, YB, Cutler, CS, Gale, RP, Ganguly, S, Hamadani, M, Inamoto, Y, Jagasia, M, Kamble, R, Koreth, J, Lazarus, HM, Liesveld, J, Litzow, MR, Marks, DI, Nishihori, T, Olsson, RF, Reshef, R, Rowe, JM, Saad, AA, Sabloff, M, Schouten, HC, Shea, TC, Soiffer, RJ, Uy, GL, Waller, EK, Wiernik, PH, Wirk, B, Woolfrey, AE, Bunjes, D, Devine, S, de Lima, M, Sandmaier, BM, Weisdorf, D, Khoury, HJ & Saber, W 2016, 'Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis', Cancer, vol. 122, no. 19, pp. 3005-3014. https://doi.org/10.1002/cncr.30140

@article{081386b75a034835a8a94c1fbbbe53dc,

title = "Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis",

abstract = "BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P5.04; relative risk, 1.60 [95% CI, 1.15-2.22]; P5.0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P5.20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.",

keywords = "1 more, Acute myeloid leukemia, Allogeneic stem cell transplantation, FMS-like tyrosine kinase 3 (FLT3)",

author = "Abhinav Deol and Salyka Sengsayadeth and Ahn, {Kwang Woo} and Wang, {Hai Lin} and Mahmoud Aljurf and Antin, {Joseph Harry} and Minoo Battiwalla and Martin Bornhauser and Cahn, {Jean Yves} and Bruce Camitta and Chen, {Yi Bin} and Cutler, {Corey S.} and Gale, {Robert Peter} and Siddhartha Ganguly and Mehdi Hamadani and Yoshihiro Inamoto and Madan Jagasia and Rammurti Kamble and John Koreth and Lazarus, {Hillard M.} and Jane Liesveld and Litzow, {Mark R.} and Marks, {David I.} and Taiga Nishihori and Olsson, {Richard F.} and Ran Reshef and Rowe, {Jacob M.} and Saad, {Ayman A.} and Mitchell Sabloff and Schouten, {Harry C.} and Shea, {Thomas C.} and Soiffer, {Robert J.} and Uy, {Geoffrey L.} and Waller, {Edmond K.} and Wiernik, {Peter H.} and Baldeep Wirk and Woolfrey, {Ann E.} and Donald Bunjes and Steven Devine and {de Lima}, Marcos and Sandmaier, {Brenda M.} and Dan Weisdorf and Khoury, {Hanna Jean} and Wael Saber",

note = "Funding Information: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by a Public Health Service grant (cooperative agreement 5U24-CA076518) from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); by the NHLIB and the NCI (grant/cooperative agreement 5U10HL069294); by the Health Resources and Services Administration/Department of Health and Human Services (contract HHSH250201200016C; grants N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; by an anonymous donation to the Medical College of Wisconsin; and by grants from Alexion; Amgen, Inc (a corporate member); Be the Match Foundation; Bristol-Myers Squibb Oncology (a corporate member); Celgene Corporation (a corporate member); Chimerix, Inc (a corporate member); the Fred Hutchinson Cancer Research Center; Gamida Cell Ltd; Genentech, Inc; Genzyme Corporation; Gilead Sciences, Inc (a corporate member); Health Research, Inc; the Roswell Park Cancer Institute; HistoGenetics, Inc; Incyte Corporation; Jazz Pharmaceuticals, Inc (a corporate member); Jeff Gordon Children{\textquoteright}s Foundation; The Leukemia and Lymphoma Society; The Medical College of Wisconsin; Merck and Company, Inc; Mesoblast; Millennium: The Takeda Oncology Company; Miltenyi Biotec, Inc (a corporate member); the National Marrow Donor Program; Neovii Biotech NA, Inc; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Health Care Solutions, Inc; Otsuka America Pharmaceutical, Inc; Otsuka Pharmaceutical Company, Ltd-Japan; Oxford Immunotec; Perkin Elmer, Inc; Pharmacyclics; Sanofi US (a corporate member); Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc (a corporate member); St Baldrick{\textquoteright}s Foundation; Sunesis Pharmaceuticals, Inc (a corporate member); Swedish Orphan Biovitrum, Inc; Telomere Diagnostics, Inc; TerumoBCT; Therakos, Inc; the University of Minnesota; and Wellpoint, Inc (a corporate member). Publisher Copyright: {\textcopyright} 2016 American Cancer Society.",

year = "2016",

month = oct,

doi = "10.1002/cncr.30140",

language = "English (US)",

volume = "122",

pages = "3005--3014",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "19",

}

TY - JOUR

T1 - Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis

AU - Deol, Abhinav

AU - Sengsayadeth, Salyka

AU - Ahn, Kwang Woo

AU - Wang, Hai Lin

AU - Aljurf, Mahmoud

AU - Antin, Joseph Harry

AU - Battiwalla, Minoo

AU - Bornhauser, Martin

AU - Cahn, Jean Yves

AU - Camitta, Bruce

AU - Chen, Yi Bin

AU - Cutler, Corey S.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Hamadani, Mehdi

AU - Inamoto, Yoshihiro

AU - Jagasia, Madan

AU - Kamble, Rammurti

AU - Koreth, John

AU - Lazarus, Hillard M.

AU - Liesveld, Jane

AU - Litzow, Mark R.

AU - Marks, David I.

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Reshef, Ran

AU - Rowe, Jacob M.

AU - Saad, Ayman A.

AU - Sabloff, Mitchell

AU - Schouten, Harry C.

AU - Shea, Thomas C.

AU - Soiffer, Robert J.

AU - Uy, Geoffrey L.

AU - Waller, Edmond K.

AU - Wiernik, Peter H.

AU - Wirk, Baldeep

AU - Woolfrey, Ann E.

AU - Bunjes, Donald

AU - Devine, Steven

AU - de Lima, Marcos

AU - Sandmaier, Brenda M.

AU - Weisdorf, Dan

AU - Khoury, Hanna Jean

AU - Saber, Wael

N1 - Funding Information: The Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by a Public Health Service grant (cooperative agreement 5U24-CA076518) from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); by the NHLIB and the NCI (grant/cooperative agreement 5U10HL069294); by the Health Resources and Services Administration/Department of Health and Human Services (contract HHSH250201200016C; grants N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; by an anonymous donation to the Medical College of Wisconsin; and by grants from Alexion; Amgen, Inc (a corporate member); Be the Match Foundation; Bristol-Myers Squibb Oncology (a corporate member); Celgene Corporation (a corporate member); Chimerix, Inc (a corporate member); the Fred Hutchinson Cancer Research Center; Gamida Cell Ltd; Genentech, Inc; Genzyme Corporation; Gilead Sciences, Inc (a corporate member); Health Research, Inc; the Roswell Park Cancer Institute; HistoGenetics, Inc; Incyte Corporation; Jazz Pharmaceuticals, Inc (a corporate member); Jeff Gordon Children’s Foundation; The Leukemia and Lymphoma Society; The Medical College of Wisconsin; Merck and Company, Inc; Mesoblast; Millennium: The Takeda Oncology Company; Miltenyi Biotec, Inc (a corporate member); the National Marrow Donor Program; Neovii Biotech NA, Inc; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Health Care Solutions, Inc; Otsuka America Pharmaceutical, Inc; Otsuka Pharmaceutical Company, Ltd-Japan; Oxford Immunotec; Perkin Elmer, Inc; Pharmacyclics; Sanofi US (a corporate member); Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc (a corporate member); St Baldrick’s Foundation; Sunesis Pharmaceuticals, Inc (a corporate member); Swedish Orphan Biovitrum, Inc; Telomere Diagnostics, Inc; TerumoBCT; Therakos, Inc; the University of Minnesota; and Wellpoint, Inc (a corporate member). Publisher Copyright: © 2016 American Cancer Society.

PY - 2016/10

Y1 - 2016/10

N2 - BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P5.04; relative risk, 1.60 [95% CI, 1.15-2.22]; P5.0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P5.20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.

AB - BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P5.04; relative risk, 1.60 [95% CI, 1.15-2.22]; P5.0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P5.20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.

KW - 1 more

KW - Acute myeloid leukemia

KW - Allogeneic stem cell transplantation

KW - FMS-like tyrosine kinase 3 (FLT3)

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UR - http://www.scopus.com/inward/citedby.url?scp=84978397912&partnerID=8YFLogxK

U2 - 10.1002/cncr.30140

DO - 10.1002/cncr.30140

M3 - Article

C2 - 27315441

AN - SCOPUS:84978397912

SN - 0008-543X

VL - 122

SP - 3005

EP - 3014

JO - Cancer

JF - Cancer

IS - 19

ER -

Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A center for international blood and marrow transplant research (CIBMTR) analysis

Abstract

Bibliographical note

Keywords

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