The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

Moshe Yeshurun; Daniel Weisdorf; Jacob M. Rowe; Martin S. Tallman; Mei Jie Zhang; Hai Lin Wang; Wael Saber; Marcos De Lima; Brenda M. Sandmaier; Geoffrey Uy; Rammurti T. Kamble; Mitchell S. Cairo; Brenda W. Cooper; Jean Yves Cahn; Siddhartha Ganguly; Bruce Camitta; Leo F. Verdonck; Christopher Dandoy; Miguel Angel Diaz; Bipin N. Savani; Biju George; Jane Liesveld; Joseph McGuirk; Michael Byrne; Michael R. Grunwald; William R. Drobyski; Michael A. Pulsipher; Hisham Abdel-Azim; Tim Prestidge; Matthew J. Wieduwilt; Rodrigo Martino; Maxim Norkin; Amer Beitinjaneh; Sachiko Seo; Taiga Nishihori; Baldeep Wirk; Haydar Frangoul; Asad Bashey; Shahram Mori; David I. Marks; Veronika Bachanova

doi:10.1182/bloodadvances.2018027003

The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

Moshe Yeshurun, Daniel Weisdorf, Jacob M. Rowe, Martin S. Tallman, Mei Jie Zhang, Hai Lin Wang, Wael Saber, Marcos De Lima, Brenda M. Sandmaier, Geoffrey Uy, Rammurti T. Kamble, Mitchell S. Cairo, Brenda W. Cooper, Jean Yves Cahn, Siddhartha Ganguly, Bruce Camitta, Leo F. Verdonck, Christopher Dandoy, Miguel Angel Diaz, Bipin N. SavaniBiju George, Jane Liesveld, Joseph McGuirk, Michael Byrne, Michael R. Grunwald, William R. Drobyski, Michael A. Pulsipher, Hisham Abdel-Azim, Tim Prestidge, Matthew J. Wieduwilt, Rodrigo Martino, Maxim Norkin, Amer Beitinjaneh, Sachiko Seo, Taiga Nishihori, Baldeep Wirk, Haydar Frangoul, Asad Bashey, Shahram Mori, David I. Marks, Veronika Bachanova

Medicine - Hematology, Oncology, Transplant

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

57 Scopus citations

Abstract

Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR $3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

Original language	English (US)
Pages (from-to)	670-680
Number of pages	11
Journal	Blood Advances
Volume	3
Issue number	4
DOIs	https://doi.org/10.1182/bloodadvances.2018027003
State	Published - Feb 26 2019

Bibliographical note

Publisher Copyright:
© 2019 by The American Society of Hematology.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1182/bloodadvances.2018027003

OpenUrl availability

Full text

Cite this

Yeshurun, M., Weisdorf, D., Rowe, J. M., Tallman, M. S., Zhang, M. J., Wang, H. L., Saber, W., De Lima, M., Sandmaier, B. M., Uy, G., Kamble, R. T., Cairo, M. S., Cooper, B. W., Cahn, J. Y., Ganguly, S., Camitta, B., Verdonck, L. F., Dandoy, C., Diaz, M. A., ... Bachanova, V. (2019). The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia. Blood Advances, 3(4), 670-680. https://doi.org/10.1182/bloodadvances.2018027003

Yeshurun, M, Weisdorf, D, Rowe, JM, Tallman, MS, Zhang, MJ, Wang, HL, Saber, W, De Lima, M, Sandmaier, BM, Uy, G, Kamble, RT, Cairo, MS, Cooper, BW, Cahn, JY, Ganguly, S, Camitta, B, Verdonck, LF, Dandoy, C, Diaz, MA, Savani, BN, George, B, Liesveld, J, McGuirk, J, Byrne, M, Grunwald, MR, Drobyski, WR, Pulsipher, MA, Abdel-Azim, H, Prestidge, T, Wieduwilt, MJ, Martino, R, Norkin, M, Beitinjaneh, A, Seo, S, Nishihori, T, Wirk, B, Frangoul, H, Bashey, A, Mori, S, Marks, DI & Bachanova, V 2019, 'The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia', Blood Advances, vol. 3, no. 4, pp. 670-680. https://doi.org/10.1182/bloodadvances.2018027003

@article{9e8388a25c3c4d5dad28bdf6e065ff33,

title = "The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia",

abstract = "Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR $3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.",

author = "Moshe Yeshurun and Daniel Weisdorf and Rowe, {Jacob M.} and Tallman, {Martin S.} and Zhang, {Mei Jie} and Wang, {Hai Lin} and Wael Saber and {De Lima}, Marcos and Sandmaier, {Brenda M.} and Geoffrey Uy and Kamble, {Rammurti T.} and Cairo, {Mitchell S.} and Cooper, {Brenda W.} and Cahn, {Jean Yves} and Siddhartha Ganguly and Bruce Camitta and Verdonck, {Leo F.} and Christopher Dandoy and Diaz, {Miguel Angel} and Savani, {Bipin N.} and Biju George and Jane Liesveld and Joseph McGuirk and Michael Byrne and Grunwald, {Michael R.} and Drobyski, {William R.} and Pulsipher, {Michael A.} and Hisham Abdel-Azim and Tim Prestidge and Wieduwilt, {Matthew J.} and Rodrigo Martino and Maxim Norkin and Amer Beitinjaneh and Sachiko Seo and Taiga Nishihori and Baldeep Wirk and Haydar Frangoul and Asad Bashey and Shahram Mori and Marks, {David I.} and Veronika Bachanova",

note = "Publisher Copyright: {\textcopyright} 2019 by The American Society of Hematology.",

year = "2019",

month = feb,

day = "26",

doi = "10.1182/bloodadvances.2018027003",

language = "English (US)",

volume = "3",

pages = "670--680",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "4",

}

TY - JOUR

T1 - The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

AU - Yeshurun, Moshe

AU - Weisdorf, Daniel

AU - Rowe, Jacob M.

AU - Tallman, Martin S.

AU - Zhang, Mei Jie

AU - Wang, Hai Lin

AU - Saber, Wael

AU - De Lima, Marcos

AU - Sandmaier, Brenda M.

AU - Uy, Geoffrey

AU - Kamble, Rammurti T.

AU - Cairo, Mitchell S.

AU - Cooper, Brenda W.

AU - Cahn, Jean Yves

AU - Ganguly, Siddhartha

AU - Camitta, Bruce

AU - Verdonck, Leo F.

AU - Dandoy, Christopher

AU - Diaz, Miguel Angel

AU - Savani, Bipin N.

AU - George, Biju

AU - Liesveld, Jane

AU - McGuirk, Joseph

AU - Byrne, Michael

AU - Grunwald, Michael R.

AU - Drobyski, William R.

AU - Pulsipher, Michael A.

AU - Abdel-Azim, Hisham

AU - Prestidge, Tim

AU - Wieduwilt, Matthew J.

AU - Martino, Rodrigo

AU - Norkin, Maxim

AU - Beitinjaneh, Amer

AU - Seo, Sachiko

AU - Nishihori, Taiga

AU - Wirk, Baldeep

AU - Frangoul, Haydar

AU - Bashey, Asad

AU - Mori, Shahram

AU - Marks, David I.

AU - Bachanova, Veronika

PY - 2019/2/26

Y1 - 2019/2/26

N2 - Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR $3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

AB - Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR $3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

UR - http://www.scopus.com/inward/record.url?scp=85062250569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062250569&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2018027003

DO - 10.1182/bloodadvances.2018027003

M3 - Article

C2 - 30808685

AN - SCOPUS:85062250569

SN - 2473-9529

VL - 3

SP - 670

EP - 680

JO - Blood Advances

JF - Blood Advances

IS - 4

ER -

The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

Abstract

Bibliographical note

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this