Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients: Center for International blood and marrow transplant research report

Haesook T. Kim, Kwang Woo Ahn, Zhen Huan Hu, Matthew S. Davids, Virginia O. Volpe, Joseph H. Antin, Mohamed L. Sorror, Mazyar Shadman, Oliver Press, Joseph Pidala, William Hogan, Robert Negrin, Steven Devine, Joseph Uberti, Edward Agura, Richard Nash, Jayesh Mehta, Joseph McGuirk, Stephen Forman, Amelia LangstonSergio A. Giralt, Miguel Angel Perales, Minoo Battiwalla, Gregory A. Hale, Robert Peter Gale, David I. Marks, Mehdi Hamadani, Sid Ganguly, Ulrike Bacher, Hillard Lazarus, Ran Reshef, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Jean Yves Cahn, Melhem Solh, Mohamed A. Kharfan-Dabaja, Nilanjan Ghosh, Ayman Saad, Mahmoud Aljurf, Harry C. Schouten, Brian T. Hill, Attaphol Pawarode, Tamila Kindwall-Keller, Nakhle Saba, Edward A. Copelan, Sunita Nathan, Amer Beitinjaneh, Bipin N. Savani, Jan Cerny, Michael R. Grunwald, Jean Yared, Baldeep M. Wirk, Taiga Nishihori, Saurabh Chhabra, Richard F. Olsson, Asad Bashey, Usama Gergis, Uday Popat, Ronald Sobecks, Edwin Alyea, Wael Saber, Jennifer R. Brown

Research output: Contribution to journalArticle

Abstract

Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

Original languageEnglish (US)
Pages (from-to)5143-5155
Number of pages13
JournalClinical Cancer Research
Volume25
Issue number16
DOIs
StatePublished - Aug 15 2019

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B-Cell Chronic Lymphocytic Leukemia
Cytogenetics
Cell Transplantation
Bone Marrow
Transplants
Disease-Free Survival
Hematopoietic System
Benchmarking
Survival
Lymphocyte Count
Leukocyte Count
Comorbidity
Counseling
Research Design
Research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients : Center for International blood and marrow transplant research report. / Kim, Haesook T.; Ahn, Kwang Woo; Hu, Zhen Huan; Davids, Matthew S.; Volpe, Virginia O.; Antin, Joseph H.; Sorror, Mohamed L.; Shadman, Mazyar; Press, Oliver; Pidala, Joseph; Hogan, William; Negrin, Robert; Devine, Steven; Uberti, Joseph; Agura, Edward; Nash, Richard; Mehta, Jayesh; McGuirk, Joseph; Forman, Stephen; Langston, Amelia; Giralt, Sergio A.; Perales, Miguel Angel; Battiwalla, Minoo; Hale, Gregory A.; Gale, Robert Peter; Marks, David I.; Hamadani, Mehdi; Ganguly, Sid; Bacher, Ulrike; Lazarus, Hillard; Reshef, Ran; Hildebrandt, Gerhard C.; Inamoto, Yoshihiro; Cahn, Jean Yves; Solh, Melhem; Kharfan-Dabaja, Mohamed A.; Ghosh, Nilanjan; Saad, Ayman; Aljurf, Mahmoud; Schouten, Harry C.; Hill, Brian T.; Pawarode, Attaphol; Kindwall-Keller, Tamila; Saba, Nakhle; Copelan, Edward A.; Nathan, Sunita; Beitinjaneh, Amer; Savani, Bipin N.; Cerny, Jan; Grunwald, Michael R.; Yared, Jean; Wirk, Baldeep M.; Nishihori, Taiga; Chhabra, Saurabh; Olsson, Richard F.; Bashey, Asad; Gergis, Usama; Popat, Uday; Sobecks, Ronald; Alyea, Edwin; Saber, Wael; Brown, Jennifer R.

In: Clinical Cancer Research, Vol. 25, No. 16, 15.08.2019, p. 5143-5155.

Research output: Contribution to journalArticle

Kim, HT, Ahn, KW, Hu, ZH, Davids, MS, Volpe, VO, Antin, JH, Sorror, ML, Shadman, M, Press, O, Pidala, J, Hogan, W, Negrin, R, Devine, S, Uberti, J, Agura, E, Nash, R, Mehta, J, McGuirk, J, Forman, S, Langston, A, Giralt, SA, Perales, MA, Battiwalla, M, Hale, GA, Gale, RP, Marks, DI, Hamadani, M, Ganguly, S, Bacher, U, Lazarus, H, Reshef, R, Hildebrandt, GC, Inamoto, Y, Cahn, JY, Solh, M, Kharfan-Dabaja, MA, Ghosh, N, Saad, A, Aljurf, M, Schouten, HC, Hill, BT, Pawarode, A, Kindwall-Keller, T, Saba, N, Copelan, EA, Nathan, S, Beitinjaneh, A, Savani, BN, Cerny, J, Grunwald, MR, Yared, J, Wirk, BM, Nishihori, T, Chhabra, S, Olsson, RF, Bashey, A, Gergis, U, Popat, U, Sobecks, R, Alyea, E, Saber, W & Brown, JR 2019, 'Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients: Center for International blood and marrow transplant research report', Clinical Cancer Research, vol. 25, no. 16, pp. 5143-5155. https://doi.org/10.1158/1078-0432.CCR-18-3988
Kim, Haesook T. ; Ahn, Kwang Woo ; Hu, Zhen Huan ; Davids, Matthew S. ; Volpe, Virginia O. ; Antin, Joseph H. ; Sorror, Mohamed L. ; Shadman, Mazyar ; Press, Oliver ; Pidala, Joseph ; Hogan, William ; Negrin, Robert ; Devine, Steven ; Uberti, Joseph ; Agura, Edward ; Nash, Richard ; Mehta, Jayesh ; McGuirk, Joseph ; Forman, Stephen ; Langston, Amelia ; Giralt, Sergio A. ; Perales, Miguel Angel ; Battiwalla, Minoo ; Hale, Gregory A. ; Gale, Robert Peter ; Marks, David I. ; Hamadani, Mehdi ; Ganguly, Sid ; Bacher, Ulrike ; Lazarus, Hillard ; Reshef, Ran ; Hildebrandt, Gerhard C. ; Inamoto, Yoshihiro ; Cahn, Jean Yves ; Solh, Melhem ; Kharfan-Dabaja, Mohamed A. ; Ghosh, Nilanjan ; Saad, Ayman ; Aljurf, Mahmoud ; Schouten, Harry C. ; Hill, Brian T. ; Pawarode, Attaphol ; Kindwall-Keller, Tamila ; Saba, Nakhle ; Copelan, Edward A. ; Nathan, Sunita ; Beitinjaneh, Amer ; Savani, Bipin N. ; Cerny, Jan ; Grunwald, Michael R. ; Yared, Jean ; Wirk, Baldeep M. ; Nishihori, Taiga ; Chhabra, Saurabh ; Olsson, Richard F. ; Bashey, Asad ; Gergis, Usama ; Popat, Uday ; Sobecks, Ronald ; Alyea, Edwin ; Saber, Wael ; Brown, Jennifer R. / Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients : Center for International blood and marrow transplant research report. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 16. pp. 5143-5155.
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title = "Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients: Center for International blood and marrow transplant research report",
abstract = "Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58{\%}, 42{\%}, 33{\%}, and 25{\%}, respectively, P < 0.0001; 4-year overall survival (OS) 70{\%}, 57{\%}, 54{\%}, and 38{\%}, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61{\%} at 4 years) and OS (75{\%} at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.",
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TY - JOUR

T1 - Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients

T2 - Center for International blood and marrow transplant research report

AU - Kim, Haesook T.

AU - Ahn, Kwang Woo

AU - Hu, Zhen Huan

AU - Davids, Matthew S.

AU - Volpe, Virginia O.

AU - Antin, Joseph H.

AU - Sorror, Mohamed L.

AU - Shadman, Mazyar

AU - Press, Oliver

AU - Pidala, Joseph

AU - Hogan, William

AU - Negrin, Robert

AU - Devine, Steven

AU - Uberti, Joseph

AU - Agura, Edward

AU - Nash, Richard

AU - Mehta, Jayesh

AU - McGuirk, Joseph

AU - Forman, Stephen

AU - Langston, Amelia

AU - Giralt, Sergio A.

AU - Perales, Miguel Angel

AU - Battiwalla, Minoo

AU - Hale, Gregory A.

AU - Gale, Robert Peter

AU - Marks, David I.

AU - Hamadani, Mehdi

AU - Ganguly, Sid

AU - Bacher, Ulrike

AU - Lazarus, Hillard

AU - Reshef, Ran

AU - Hildebrandt, Gerhard C.

AU - Inamoto, Yoshihiro

AU - Cahn, Jean Yves

AU - Solh, Melhem

AU - Kharfan-Dabaja, Mohamed A.

AU - Ghosh, Nilanjan

AU - Saad, Ayman

AU - Aljurf, Mahmoud

AU - Schouten, Harry C.

AU - Hill, Brian T.

AU - Pawarode, Attaphol

AU - Kindwall-Keller, Tamila

AU - Saba, Nakhle

AU - Copelan, Edward A.

AU - Nathan, Sunita

AU - Beitinjaneh, Amer

AU - Savani, Bipin N.

AU - Cerny, Jan

AU - Grunwald, Michael R.

AU - Yared, Jean

AU - Wirk, Baldeep M.

AU - Nishihori, Taiga

AU - Chhabra, Saurabh

AU - Olsson, Richard F.

AU - Bashey, Asad

AU - Gergis, Usama

AU - Popat, Uday

AU - Sobecks, Ronald

AU - Alyea, Edwin

AU - Saber, Wael

AU - Brown, Jennifer R.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

AB - Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

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