Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research

Hemant S. Murthy; Kwang Woo Ahn; Noel Estrada-Merly; Hassan B. Alkhateeb; Susan Bal; Mohamed A. Kharfan-Dabaja; Bhagirathbhai Dholaria; Francine Foss; Lohith Gowda; Deepa Jagadeesh; Craig Sauter; Muhammad Bilal Abid; Mahmoud Aljurf; Farrukh T. Awan; Ulrike Bacher; Sherif M. Badawy; Minoo Battiwalla; Chris Bredeson; Jan Cerny; Saurabh Chhabra; Abhinav Deol; Miguel Angel Diaz; Nosha Farhadfar; César Freytes; James Gajewski; Manish J. Gandhi; Siddhartha Ganguly; Michael R. Grunwald; Joerg Halter; Shahrukh Hashmi; Gerhard C. Hildebrandt; Yoshihiro Inamoto; Antonio Martin Jimenez-Jimenez; Matt Kalaycio; Rammurti Kamble; Maxwell M. Krem; Hillard M. Lazarus; Aleksandr Lazaryan; Joseph Maakaron; Pashna N. Munshi; Reinhold Munker; Aziz Nazha; Taiga Nishihori; Olalekan O. Oluwole; Guillermo Ortí; Dorothy C. Pan; Sagar S. Patel; Attaphol Pawarode; David Rizzieri; Nakhle S. Saba; Bipin Savani; Sachiko Seo; Celalettin Ustun; Marjolein van der Poel; Leo F. Verdonck; John L. Wagner; Baldeep Wirk; Betul Oran; Ryotaro Nakamura; Bart Scott; Wael Saber

doi:10.1016/j.jtct.2022.01.017

Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research

Hemant S. Murthy, Kwang Woo Ahn, Noel Estrada-Merly, Hassan B. Alkhateeb, Susan Bal, Mohamed A. Kharfan-Dabaja, Bhagirathbhai Dholaria, Francine Foss, Lohith Gowda, Deepa Jagadeesh, Craig Sauter, Muhammad Bilal Abid, Mahmoud Aljurf, Farrukh T. Awan, Ulrike Bacher, Sherif M. Badawy, Minoo Battiwalla, Chris Bredeson, Jan Cerny, Saurabh ChhabraAbhinav Deol, Miguel Angel Diaz, Nosha Farhadfar, César Freytes, James Gajewski, Manish J. Gandhi, Siddhartha Ganguly, Michael R. Grunwald, Joerg Halter, Shahrukh Hashmi, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Antonio Martin Jimenez-Jimenez, Matt Kalaycio, Rammurti Kamble, Maxwell M. Krem, Hillard M. Lazarus, Aleksandr Lazaryan, Joseph Maakaron, Pashna N. Munshi, Reinhold Munker, Aziz Nazha, Taiga Nishihori, Olalekan O. Oluwole, Guillermo Ortí, Dorothy C. Pan, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Nakhle S. Saba, Bipin Savani, Sachiko Seo, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, John L. Wagner, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber

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

8 Scopus citations

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	https://doi.org/10.1016/j.jtct.2022.01.017
State	Published - Apr 2022

Bibliographical note

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

Keywords

Allogeneic stem cell transplant
Prolymphocytic leukemia
T-PLL

UN SDGs

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

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10.1016/j.jtct.2022.01.017

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Murthy, H. S., Ahn, K. W., Estrada-Merly, N., Alkhateeb, H. B., Bal, S., Kharfan-Dabaja, M. A., Dholaria, B., Foss, F., Gowda, L., Jagadeesh, D., Sauter, C., Abid, M. B., Aljurf, M., Awan, F. T., Bacher, U., Badawy, S. M., Battiwalla, M., Bredeson, C., Cerny, J., ... Saber, W. (2022). Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research. Transplantation and Cellular Therapy, 28(4), 187.e1-187.e10. https://doi.org/10.1016/j.jtct.2022.01.017

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

Murthy, HS, Ahn, KW, Estrada-Merly, N, Alkhateeb, HB, Bal, S, Kharfan-Dabaja, MA, Dholaria, B, Foss, F, Gowda, L, Jagadeesh, D, Sauter, C, Abid, MB, Aljurf, M, Awan, FT, Bacher, U, Badawy, SM, Battiwalla, M, Bredeson, C, Cerny, J, Chhabra, S, Deol, A, Diaz, MA, Farhadfar, N, Freytes, C, Gajewski, J, Gandhi, MJ, Ganguly, S, Grunwald, MR, Halter, J, Hashmi, S, Hildebrandt, GC, Inamoto, Y, Jimenez-Jimenez, AM, Kalaycio, M, Kamble, R, Krem, MM, Lazarus, HM, Lazaryan, A, Maakaron, J, Munshi, PN, Munker, R, Nazha, A, Nishihori, T, Oluwole, OO, Ortí, G, Pan, DC, Patel, SS, Pawarode, A, Rizzieri, D, Saba, NS, Savani, B, Seo, S, Ustun, C, van der Poel, M, Verdonck, LF, Wagner, JL, Wirk, B, Oran, B, Nakamura, R, Scott, B & Saber, W 2022, 'Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research', Transplantation and Cellular Therapy, vol. 28, no. 4, pp. 187.e1-187.e10. https://doi.org/10.1016/j.jtct.2022.01.017

Murthy HS, Ahn KW, Estrada-Merly N, Alkhateeb HB, Bal S, Kharfan-Dabaja MA et al. Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research. Transplantation and Cellular Therapy. 2022 Apr;28(4):187.e1-187.e10. doi: 10.1016/j.jtct.2022.01.017

@article{8bdfbf1a7ad14adab9c848366e09d7de,

title = "Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research",

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.",

keywords = "Allogeneic stem cell transplant, Prolymphocytic leukemia, T-PLL",

author = "Murthy, {Hemant S.} and Ahn, {Kwang Woo} and Noel Estrada-Merly and Alkhateeb, {Hassan B.} and Susan Bal and Kharfan-Dabaja, {Mohamed A.} and Bhagirathbhai Dholaria and Francine Foss and Lohith Gowda and Deepa Jagadeesh and Craig Sauter and Abid, {Muhammad Bilal} and Mahmoud Aljurf and Awan, {Farrukh T.} and Ulrike Bacher and Badawy, {Sherif M.} and Minoo Battiwalla and Chris Bredeson and Jan Cerny and Saurabh Chhabra and Abhinav Deol and Diaz, {Miguel Angel} and Nosha Farhadfar and C{\'e}sar Freytes and James Gajewski and Gandhi, {Manish J.} and Siddhartha Ganguly and Grunwald, {Michael R.} and Joerg Halter and Shahrukh Hashmi and Hildebrandt, {Gerhard C.} and Yoshihiro Inamoto and Jimenez-Jimenez, {Antonio Martin} and Matt Kalaycio and Rammurti Kamble and Krem, {Maxwell M.} and Lazarus, {Hillard M.} and Aleksandr Lazaryan and Joseph Maakaron and Munshi, {Pashna N.} and Reinhold Munker and Aziz Nazha and Taiga Nishihori and Oluwole, {Olalekan O.} and Guillermo Ort{\'i} and Pan, {Dorothy C.} and Patel, {Sagar S.} and Attaphol Pawarode and David Rizzieri and Saba, {Nakhle S.} and Bipin Savani and Sachiko Seo and Celalettin Ustun and {van der Poel}, Marjolein and Verdonck, {Leo F.} and Wagner, {John L.} and Baldeep Wirk and Betul Oran and Ryotaro Nakamura and Bart Scott and Wael Saber",

note = "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: {\textcopyright} 2022 The American Society for Transplantation and Cellular Therapy",

year = "2022",

month = apr,

doi = "10.1016/j.jtct.2022.01.017",

language = "English (US)",

volume = "28",

pages = "187.e1--187.e10",

journal = "Transplantation and Cellular Therapy",

issn = "2666-6367",

publisher = "Elsevier BV",

number = "4",

}

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

SN - 2666-6367

VL - 28

SP - 187.e1-187.e10

JO - Transplantation and Cellular Therapy

JF - Transplantation and Cellular Therapy

IS - 4

ER -

Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research

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