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 Langston; Sergio 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

doi:10.1158/1078-0432.CCR-18-3988

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

^*Corresponding author for this work

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

7 Citations (Web of Science)

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 language	English
Pages (from-to)	5143-5155
Number of pages	13
Journal	Clinical Cancer Research
Volume	25
Issue number	16
DOIs	https://doi.org/10.1158/1078-0432.CCR-18-3988
Publication status	Published - 15 Aug 2019

Keywords

STEM-CELL TRANSPLANTATION
FOLLOW-UP
CLL
PREDICTS
SURVIVAL
MODEL

Access to Document

10.1158/1078-0432.CCR-18-3988

Cite this

Kim, H. T., Ahn, K. W., Hu, Z-H., Davids, M. S., Volpe, V. O., Antin, J. H., Sorror, M. L., Shadman, M., Press, O., Pidala, J., Hogan, W., Negrin, R., Devine, S., Uberti, J., Agura, E., Nash, R., Mehta, J., McGuirk, J., Forman, S., ... Brown, J. R. (2019). Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report. Clinical Cancer Research, 25(16), 5143-5155. https://doi.org/10.1158/1078-0432.CCR-18-3988

@article{f22be8152f01436e87c3af5adc3448a0,

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.",

keywords = "STEM-CELL TRANSPLANTATION, FOLLOW-UP, CLL, PREDICTS, SURVIVAL, MODEL",

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

year = "2019",

month = aug,

day = "15",

doi = "10.1158/1078-0432.CCR-18-3988",

language = "English",

volume = "25",

pages = "5143--5155",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "16",

}

Kim, HT, Ahn, KW, Hu, Z-H, 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, M-A, Battiwalla, M, Hale, GA, Gale, RP, Marks, DI, Hamadani, M, Ganguly, S, Bacher, U, Lazarus, H, Reshef, R, Hildebrandt, GC, Inamoto, Y, Cahn, J-Y, 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

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 et al.

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

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

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.

KW - STEM-CELL TRANSPLANTATION

KW - FOLLOW-UP

KW - CLL

KW - PREDICTS

KW - SURVIVAL

KW - MODEL

U2 - 10.1158/1078-0432.CCR-18-3988

DO - 10.1158/1078-0432.CCR-18-3988

M3 - Article

C2 - 31253630

VL - 25

SP - 5143

EP - 5155

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 16

ER -