GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia

Rohtesh S. Mehta, Shernan G. Holtan, Tao Wang, Michael T. Hemmer, Stephen R. Spellman, Mukta Arora, Daniel R. Couriel, Amin M. Alousi, Joseph Pidala, Hisham Abdel-Azim, Ibrahim Ahmed, Mahmoud Aljurf, Medhat Askar, Jeffery J. Auletta, Vijaya Bhatt, Christopher Bredeson, Saurabh Chhabra, Shahinaz Gadalla, James Gajewski, Robert Peter GaleUsama Gergis, Peiman Hematti, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Carrie Kitko, Pooja Khandelwal, Margaret L. MacMillan, Navneet Majhail, David I. Marks, Parinda Mehta, Taiga Nishihori, Richard F. Olsson, Attaphol Pawarode, Miguel Angel Diaz, Tim Prestidge, Muna Qayed, Hemalatha Rangarajan, Olle Ringden, Ayman Saad, Bipin N. Savani, Sachiko Seo, Ami Shah, Niketa Shah, Kirk R. Schultz, Melhem Solh, Thomas Spitzer, Jeffrey Szer, Takanori Teshima, Leo F. Verdonck, Kirsten M. Williams, Baldeep Wirk, John Wagner, Jean A. Yared, Daniel J. Weisdorf

Research output: Contribution to journalArticle

Abstract

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

Original languageEnglish (US)
Pages (from-to)1441-1449
Number of pages9
JournalBlood Advances
Volume3
Issue number9
DOIs
StatePublished - Jan 1 2019

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Cell Transplantation
Leukemia
Tissue Donors
Pediatrics
Recurrence
Confidence Intervals
Survival
Graft vs Host Disease
Multivariate Analysis
Mycophenolic Acid
Antilymphocyte Serum
Whole-Body Irradiation
Fetal Blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Methotrexate
Transplantation
Bone Marrow
Transplants
Antigens

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Mehta, R. S., Holtan, S. G., Wang, T., Hemmer, M. T., Spellman, S. R., Arora, M., ... Weisdorf, D. J. (2019). GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia. Blood Advances, 3(9), 1441-1449. https://doi.org/10.1182/bloodadvances.2018030171
Mehta, Rohtesh S. ; Holtan, Shernan G. ; Wang, Tao ; Hemmer, Michael T. ; Spellman, Stephen R. ; Arora, Mukta ; Couriel, Daniel R. ; Alousi, Amin M. ; Pidala, Joseph ; Abdel-Azim, Hisham ; Ahmed, Ibrahim ; Aljurf, Mahmoud ; Askar, Medhat ; Auletta, Jeffery J. ; Bhatt, Vijaya ; Bredeson, Christopher ; Chhabra, Saurabh ; Gadalla, Shahinaz ; Gajewski, James ; Gale, Robert Peter ; Gergis, Usama ; Hematti, Peiman ; Hildebrandt, Gerhard C. ; Inamoto, Yoshihiro ; Kitko, Carrie ; Khandelwal, Pooja ; MacMillan, Margaret L. ; Majhail, Navneet ; Marks, David I. ; Mehta, Parinda ; Nishihori, Taiga ; Olsson, Richard F. ; Pawarode, Attaphol ; Diaz, Miguel Angel ; Prestidge, Tim ; Qayed, Muna ; Rangarajan, Hemalatha ; Ringden, Olle ; Saad, Ayman ; Savani, Bipin N. ; Seo, Sachiko ; Shah, Ami ; Shah, Niketa ; Schultz, Kirk R. ; Solh, Melhem ; Spitzer, Thomas ; Szer, Jeffrey ; Teshima, Takanori ; Verdonck, Leo F. ; Williams, Kirsten M. ; Wirk, Baldeep ; Wagner, John ; Yared, Jean A. ; Weisdorf, Daniel J. / GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia. In: Blood Advances. 2019 ; Vol. 3, No. 9. pp. 1441-1449.
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title = "GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia",
abstract = "We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62{\%}), 64{\%} received total body irradiation-based conditioning, and 60{\%} received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79{\%}) than with UCB (15{\%}), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22{\%} (95{\%} confidence interval [CI], 16-29) and 27{\%} (95{\%} CI, 20-34), respectively, with 7/8 BM and 33{\%} (95{\%} CI, 31-36) and 38{\%} (95{\%} CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95{\%} CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95{\%} CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95{\%} CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95{\%} CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95{\%} CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.",
author = "Mehta, {Rohtesh S.} and Holtan, {Shernan G.} and Tao Wang and Hemmer, {Michael T.} and Spellman, {Stephen R.} and Mukta Arora and Couriel, {Daniel R.} and Alousi, {Amin M.} and Joseph Pidala and Hisham Abdel-Azim and Ibrahim Ahmed and Mahmoud Aljurf and Medhat Askar and Auletta, {Jeffery J.} and Vijaya Bhatt and Christopher Bredeson and Saurabh Chhabra and Shahinaz Gadalla and James Gajewski and Gale, {Robert Peter} and Usama Gergis and Peiman Hematti and Hildebrandt, {Gerhard C.} and Yoshihiro Inamoto and Carrie Kitko and Pooja Khandelwal and MacMillan, {Margaret L.} and Navneet Majhail and Marks, {David I.} and Parinda Mehta and Taiga Nishihori and Olsson, {Richard F.} and Attaphol Pawarode and Diaz, {Miguel Angel} and Tim Prestidge and Muna Qayed and Hemalatha Rangarajan and Olle Ringden and Ayman Saad and Savani, {Bipin N.} and Sachiko Seo and Ami Shah and Niketa Shah and Schultz, {Kirk R.} and Melhem Solh and Thomas Spitzer and Jeffrey Szer and Takanori Teshima and Verdonck, {Leo F.} and Williams, {Kirsten M.} and Baldeep Wirk and John Wagner and Yared, {Jean A.} and Weisdorf, {Daniel J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1182/bloodadvances.2018030171",
language = "English (US)",
volume = "3",
pages = "1441--1449",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "9",

}

Mehta, RS, Holtan, SG, Wang, T, Hemmer, MT, Spellman, SR, Arora, M, Couriel, DR, Alousi, AM, Pidala, J, Abdel-Azim, H, Ahmed, I, Aljurf, M, Askar, M, Auletta, JJ, Bhatt, V, Bredeson, C, Chhabra, S, Gadalla, S, Gajewski, J, Gale, RP, Gergis, U, Hematti, P, Hildebrandt, GC, Inamoto, Y, Kitko, C, Khandelwal, P, MacMillan, ML, Majhail, N, Marks, DI, Mehta, P, Nishihori, T, Olsson, RF, Pawarode, A, Diaz, MA, Prestidge, T, Qayed, M, Rangarajan, H, Ringden, O, Saad, A, Savani, BN, Seo, S, Shah, A, Shah, N, Schultz, KR, Solh, M, Spitzer, T, Szer, J, Teshima, T, Verdonck, LF, Williams, KM, Wirk, B, Wagner, J, Yared, JA & Weisdorf, DJ 2019, 'GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia', Blood Advances, vol. 3, no. 9, pp. 1441-1449. https://doi.org/10.1182/bloodadvances.2018030171

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia. / Mehta, Rohtesh S.; Holtan, Shernan G.; Wang, Tao; Hemmer, Michael T.; Spellman, Stephen R.; Arora, Mukta; Couriel, Daniel R.; Alousi, Amin M.; Pidala, Joseph; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Askar, Medhat; Auletta, Jeffery J.; Bhatt, Vijaya; Bredeson, Christopher; Chhabra, Saurabh; Gadalla, Shahinaz; Gajewski, James; Gale, Robert Peter; Gergis, Usama; Hematti, Peiman; Hildebrandt, Gerhard C.; Inamoto, Yoshihiro; Kitko, Carrie; Khandelwal, Pooja; MacMillan, Margaret L.; Majhail, Navneet; Marks, David I.; Mehta, Parinda; Nishihori, Taiga; Olsson, Richard F.; Pawarode, Attaphol; Diaz, Miguel Angel; Prestidge, Tim; Qayed, Muna; Rangarajan, Hemalatha; Ringden, Olle; Saad, Ayman; Savani, Bipin N.; Seo, Sachiko; Shah, Ami; Shah, Niketa; Schultz, Kirk R.; Solh, Melhem; Spitzer, Thomas; Szer, Jeffrey; Teshima, Takanori; Verdonck, Leo F.; Williams, Kirsten M.; Wirk, Baldeep; Wagner, John; Yared, Jean A.; Weisdorf, Daniel J.

In: Blood Advances, Vol. 3, No. 9, 01.01.2019, p. 1441-1449.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia

AU - Mehta, Rohtesh S.

AU - Holtan, Shernan G.

AU - Wang, Tao

AU - Hemmer, Michael T.

AU - Spellman, Stephen R.

AU - Arora, Mukta

AU - Couriel, Daniel R.

AU - Alousi, Amin M.

AU - Pidala, Joseph

AU - Abdel-Azim, Hisham

AU - Ahmed, Ibrahim

AU - Aljurf, Mahmoud

AU - Askar, Medhat

AU - Auletta, Jeffery J.

AU - Bhatt, Vijaya

AU - Bredeson, Christopher

AU - Chhabra, Saurabh

AU - Gadalla, Shahinaz

AU - Gajewski, James

AU - Gale, Robert Peter

AU - Gergis, Usama

AU - Hematti, Peiman

AU - Hildebrandt, Gerhard C.

AU - Inamoto, Yoshihiro

AU - Kitko, Carrie

AU - Khandelwal, Pooja

AU - MacMillan, Margaret L.

AU - Majhail, Navneet

AU - Marks, David I.

AU - Mehta, Parinda

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Pawarode, Attaphol

AU - Diaz, Miguel Angel

AU - Prestidge, Tim

AU - Qayed, Muna

AU - Rangarajan, Hemalatha

AU - Ringden, Olle

AU - Saad, Ayman

AU - Savani, Bipin N.

AU - Seo, Sachiko

AU - Shah, Ami

AU - Shah, Niketa

AU - Schultz, Kirk R.

AU - Solh, Melhem

AU - Spitzer, Thomas

AU - Szer, Jeffrey

AU - Teshima, Takanori

AU - Verdonck, Leo F.

AU - Williams, Kirsten M.

AU - Wirk, Baldeep

AU - Wagner, John

AU - Yared, Jean A.

AU - Weisdorf, Daniel J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

AB - We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

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