Abstract
T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.
Original language | English (US) |
---|---|
Pages (from-to) | 187.e1-187.e10 |
Journal | Transplantation and Cellular Therapy |
Volume | 28 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2022 |
Keywords
- Allogeneic stem cell transplant
- Prolymphocytic leukemia
- T-PLL
ASJC Scopus subject areas
- Immunology and Allergy
- Molecular Medicine
- Hematology
- Cell Biology
- Transplantation
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Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia : A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research. / Murthy, Hemant S.; Ahn, Kwang Woo; Estrada-Merly, Noel et al.
In: Transplantation and Cellular Therapy, Vol. 28, No. 4, 04.2022, p. 187.e1-187.e10.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia
T2 - A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research
AU - Murthy, Hemant S.
AU - Ahn, Kwang Woo
AU - Estrada-Merly, Noel
AU - Alkhateeb, Hassan B.
AU - Bal, Susan
AU - Kharfan-Dabaja, Mohamed A.
AU - Dholaria, Bhagirathbhai
AU - Foss, Francine
AU - Gowda, Lohith
AU - Jagadeesh, Deepa
AU - Sauter, Craig
AU - Abid, Muhammad Bilal
AU - Aljurf, Mahmoud
AU - Awan, Farrukh T.
AU - Bacher, Ulrike
AU - Badawy, Sherif M.
AU - Battiwalla, Minoo
AU - Bredeson, Chris
AU - Cerny, Jan
AU - Chhabra, Saurabh
AU - Deol, Abhinav
AU - Diaz, Miguel Angel
AU - Farhadfar, Nosha
AU - Freytes, César
AU - Gajewski, James
AU - Gandhi, Manish J.
AU - Ganguly, Siddhartha
AU - Grunwald, Michael R.
AU - Halter, Joerg
AU - Hashmi, Shahrukh
AU - Hildebrandt, Gerhard C.
AU - Inamoto, Yoshihiro
AU - Jimenez-Jimenez, Antonio Martin
AU - Kalaycio, Matt
AU - Kamble, Rammurti
AU - Krem, Maxwell M.
AU - Lazarus, Hillard M.
AU - Lazaryan, Aleksandr
AU - Maakaron, Joseph
AU - Munshi, Pashna N.
AU - Munker, Reinhold
AU - Nazha, Aziz
AU - Nishihori, Taiga
AU - Oluwole, Olalekan O.
AU - Ortí, Guillermo
AU - Pan, Dorothy C.
AU - Patel, Sagar S.
AU - Pawarode, Attaphol
AU - Rizzieri, David
AU - Saba, Nakhle S.
AU - Savani, Bipin
AU - Seo, Sachiko
AU - Ustun, Celalettin
AU - van der Poel, Marjolein
AU - Verdonck, Leo F.
AU - Wagner, John L.
AU - Wirk, Baldeep
AU - Oran, Betul
AU - Nakamura, Ryotaro
AU - Scott, Bart
AU - Saber, Wael
N1 - Funding Information: The authors thank Jennifer Motl, the Medical College of Wisconsin (MCW), for providing editorial support, which was funded by the MCW in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3). Funding Information: Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant HHSH250201700006C from the Health Resources and Services Administration; and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, Medical College of Wisconsin, National Marrow Donor Program, and the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Adaptive Biotechnologies, Adienne SA, Allovir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida-Cell, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma, Kite Pharma, Kyowa Kirin, Legend, Magenta Therapeutics, Medac, Medexus, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis Pharmaceuticals, Omeros, Oncopeptides, Orca Biosystems, Ossium Health, Pfizer, Pharmacyclics, Priothera, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos BV. Funding Information: The authors thank Jennifer Motl, the Medical College of Wisconsin (MCW), for providing editorial support, which was funded by the MCW in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3). Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant U24CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant HHSH250201700006C from the Health Resources and Services Administration; and Awards N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, Medical College of Wisconsin, National Marrow Donor Program, and the following commercial entities: AbbVie, Accenture, Actinium Pharmaceuticals, Adaptive Biotechnologies, Adienne SA, Allovir, Amgen, Astellas Pharma US, bluebird bio, Bristol Myers Squibb, CareDx, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Eurofins Viracor, ExcellThera, Fate Therapeutics, Gamida-Cell, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen/Johnson & Johnson, Jasper Therapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Kiadis Pharma, Kite Pharma, Kyowa Kirin, Legend, Magenta Therapeutics, Medac, Medexus, Merck & Co, Millennium, Miltenyi Biotec, MorphoSys, Novartis Pharmaceuticals, Omeros, Oncopeptides, Orca Biosystems, Ossium Health, Pfizer, Pharmacyclics, Priothera, Sanofi Genzyme, Seagen, Stemcyte, Takeda Pharmaceuticals, Tscan, Vertex, Vor Biopharma, and Xenikos BV. Conflict of interest statement: F.T.A. reports personal fees from Genentech, AstraZeneca, AbbVie, Janssen, Pharmacyclics, Gilead Sciences, Kite Pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, Beigene, Johnson & Johnson, Dava Oncology, BMS, Merck, Cardinal Health, and ADCT Therapeutics outside the submitted work. B.D. reports institutional research support from Takeda, Janssen, Angiocrine, Pfizer, and Poseida. A.D. reports personal fees from Kite/Gilead, Jannsen/Johnson& Johnson, and Novartis outside the submitted work. M.R.G. reports personal fees from AbbVie, Agios, Amgen, Cardinal Health, BMS, Daiichi Sankyo, Incyte, Merck, Pfizer, Premier, Karius, Astellas, Trovagene, Stemline, and Gilead and other research funding from Incyte, Forma Therapeutics, Genentech/Roche, and Janssen outside the submitted work. Y.I. reports personal fees from Novartis, Janssen, and Meiji Seika Pharma outside the submitted work. P.N.M. reports personal fees from Kite Pharma and Incyte outside the submitted work. O.O.O. reports personal fees from Gilead, Pfizer, Spectrum, Bayer, and Curio Science outside the submitted work. T.N. reports other- (Novartis provided ?clinical trial support? and Karyopharm provided ?drug supply for clinical trial?) from Novartis and Karyopharm outside the submitted work. G.O. reports personal fees from Bristol Myers Squibb, Novartis, Incyte, and Pfizer and nonfinancial support from Incyte and Pfizer outside the submitted work. S.S. reports personal fees from Janssen Pharmaceutical outside the submitted work. S.S.P. reports personal fees from Kite Pharma outside the submitted work. D.R. reports personal fees from AbbVie, Agios, AROG, Bayer, Celgene, Celltrion/Teva, Gilead, Incyte, Jazz Pharmaceutical, Kadmon, Kite, Morphosys, Mustang, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Amgen, Acrobiotech, UCART, Chimerix, and Pharmacyclics and other: Consulting and presentation to FDA for biosimilar review (Celltrion/Teva); Research support, consultant, speakers bureau, and advisory board (Stemline) from Celltrion/Teva and Stemline outside the submitted work. C.S. reports grants from Juno Therapeutics, Celgene, Bristol-Myers Squibb, Precision Biosciences, and Sanofi Genzyme and personal fees from Precision Biosciences, Sanofi Genzyme, Juno Therapeutics, Spectrum Pharmaceuticals, Novartis, Genmab, Kite Pharma, Celgene, Gamida Cell, Karyopharm, and GlaxoSmithKline outside the submitted work. J.C. reports personal fees from Jazz Pharmaceuticals, Daiichi-Sankyo, Pfizer, Amgen, and Allovir outside the submitted work and stock ownership in Actinium Pharmaceuticals, bluebird bio, Dynavax Pharma, Atyr Pharmac, Gamida Cell, Miragen Therapeutics, Mustang Bio, Novavax, Ovid Therapeutics, Sorrento Therapeutics, TG Therapeutics, Vaxart, and Veru. G.C.H reports other: Consulting Advisory Role: Incyte, Jazz Pharmaceuticals, Morphosys, Alexion Pharmaceuticals, Karyopharm Therapeutics. Research Funding: Takeda, Jazz Pharmaceuticals, Pharmacyclics, Incyte, AstraZeneca. Travel, Accommodations, Expenses: Jazz Pharmaceuticals, Astellas Parma, Incyte, Falk Foundation, Takeda from Incyte, Morphosys, Alexion Pharmaceutical, Karyopharm, Takeda, Jazz Pharmaceutical, Pharmacyclics, AstraZeneca, Astellas Pharma, and the Falk Foundation outside the submitted work. S.B. reports grants from the Amyloidosis Foundation outside the submitted work. C.U. reports other: Honoraria from Novartis and Blueprint outside the submitted work. F.F. reports a patent on photopheresis for modulation of dendritic cells. Authorship statement: Conception and design: H.S.M. and M.A.K.-D. Financial support: CIBMTR. Collection and assembly of data: CIBMTR. Data analysis: H.S.M. S.B. M.A.K.-D. H.A. L.G. C.S. D.J. B.R.D. F.F. W.S. N.E.-M. and K.W.A. Interpretation: all authors. Manuscript writing: first draft prepared by H.S.M. S.B. M.A.K.-D. H.A. L.G. C.S. D.J. B.R.D. and F.F. All authors revised the manuscript and approved the final manuscript. Financial disclosure: See Acknowledgments on page 186.e8. Publisher Copyright: © 2022 The American Society for Transplantation and Cellular Therapy
PY - 2022/4
Y1 - 2022/4
N2 - T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.
AB - T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.
KW - Allogeneic stem cell transplant
KW - Prolymphocytic leukemia
KW - T-PLL
UR - http://www.scopus.com/inward/record.url?scp=85125344790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125344790&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.01.017
DO - 10.1016/j.jtct.2022.01.017
M3 - Article
C2 - 35081472
AN - SCOPUS:85125344790
VL - 28
SP - 187.e1-187.e10
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
SN - 2666-6367
IS - 4
ER -