Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Donal McLornan, Richard Szydlo, Linda Koster, Yves Chalandon, Marie Robin, Christine Wolschke, Dietrich Beelen, Gerard Socié, Martin Bornhäuser, Emanuele Angelucci, Dietger Niederwieser, Arnim Gerbitz, Jürgen Finke, Antonin Vitek, Maija Itälä-Remes, Aleksandar Radujkovic, Lothar Kanz, Victoria Potter, Patrice Chevallier, Matthias StelljesEefke Petersen, Stephen Robinson, Xavier Poiré, Evgeny Klyuchnikov, Juan Carlos Hernández-Boluda, Tomasz Czerw, Patrick Hayden, Nicolaus Kröger, Ibrahim Yakoub-Agha

Research output: Contribution to journalArticle

Abstract

This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P =.10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P =.08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P =.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P =.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.

Original languageEnglish
JournalBiology of Blood and Marrow Transplantation
DOIs
Publication statusPublished - Jan 1 2019

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Primary Myelofibrosis
Hematopoietic Stem Cell Transplantation
Retrospective Studies
Transplantation
Bone Marrow
Neoplasms
Survival
Recurrence
Conditioning (Psychology)
Confidence Intervals
Unrelated Donors
Mortality
Tissue Donors
Stem Cell Transplantation
Cohort Studies
Karnofsky Performance Status

Keywords

  • Myeloablative
  • Myeloproliferative
  • Reduced intensity
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis : A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. / McLornan, Donal; Szydlo, Richard; Koster, Linda; Chalandon, Yves; Robin, Marie; Wolschke, Christine; Beelen, Dietrich; Socié, Gerard; Bornhäuser, Martin; Angelucci, Emanuele; Niederwieser, Dietger; Gerbitz, Arnim; Finke, Jürgen; Vitek, Antonin; Itälä-Remes, Maija; Radujkovic, Aleksandar; Kanz, Lothar; Potter, Victoria; Chevallier, Patrice; Stelljes, Matthias; Petersen, Eefke; Robinson, Stephen; Poiré, Xavier; Klyuchnikov, Evgeny; Hernández-Boluda, Juan Carlos; Czerw, Tomasz; Hayden, Patrick; Kröger, Nicolaus; Yakoub-Agha, Ibrahim.

In: Biology of Blood and Marrow Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

McLornan, D, Szydlo, R, Koster, L, Chalandon, Y, Robin, M, Wolschke, C, Beelen, D, Socié, G, Bornhäuser, M, Angelucci, E, Niederwieser, D, Gerbitz, A, Finke, J, Vitek, A, Itälä-Remes, M, Radujkovic, A, Kanz, L, Potter, V, Chevallier, P, Stelljes, M, Petersen, E, Robinson, S, Poiré, X, Klyuchnikov, E, Hernández-Boluda, JC, Czerw, T, Hayden, P, Kröger, N & Yakoub-Agha, I 2019, 'Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2019.06.034
McLornan, Donal ; Szydlo, Richard ; Koster, Linda ; Chalandon, Yves ; Robin, Marie ; Wolschke, Christine ; Beelen, Dietrich ; Socié, Gerard ; Bornhäuser, Martin ; Angelucci, Emanuele ; Niederwieser, Dietger ; Gerbitz, Arnim ; Finke, Jürgen ; Vitek, Antonin ; Itälä-Remes, Maija ; Radujkovic, Aleksandar ; Kanz, Lothar ; Potter, Victoria ; Chevallier, Patrice ; Stelljes, Matthias ; Petersen, Eefke ; Robinson, Stephen ; Poiré, Xavier ; Klyuchnikov, Evgeny ; Hernández-Boluda, Juan Carlos ; Czerw, Tomasz ; Hayden, Patrick ; Kröger, Nicolaus ; Yakoub-Agha, Ibrahim. / Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis : A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. In: Biology of Blood and Marrow Transplantation. 2019.
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abstract = "This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35{\%}) underwent myeloablative conditioning (MAC) and 1443 (65{\%}) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41{\%}]; RIC, 552 [38{\%}]) and unrelated donors (MAC, 464 [59{\%}]; RIC, 891 [62{\%}]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28{\%} (MAC) and 31{\%} (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22{\%}/27{\%} (MAC) and 19{\%}/31{\%} (RIC; P =.10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5{\%}, 32.2{\%}, and 34.6{\%} (MAC) and 26.3{\%}, 32.8{\%}, and 34.4{\%} (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P =.08); rates at 1, 3, and 5 years were 10.9{\%}, 17.2{\%}, and 20.1{\%} (MAC) and 14{\%}, 19.7{\%}, and 23.2{\%} (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0{\%}; 95{\%} confidence interval [CI], 49.1{\%} to 56.9{\%}) and RIC (51.0{\%}; 95{\%} CI, 48.3{\%} to 53.7{\%}); P =.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4{\%} (95{\%} CI, 29.0{\%} to 36.1{\%}) in the MAC group and 26.1{\%} (95{\%} CI, 23.9{\%} to 28.2{\%}) in the RIC group (P =.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.",
keywords = "Myeloablative, Myeloproliferative, Reduced intensity, Stem cell transplantation",
author = "Donal McLornan and Richard Szydlo and Linda Koster and Yves Chalandon and Marie Robin and Christine Wolschke and Dietrich Beelen and Gerard Soci{\'e} and Martin Bornh{\"a}user and Emanuele Angelucci and Dietger Niederwieser and Arnim Gerbitz and J{\"u}rgen Finke and Antonin Vitek and Maija It{\"a}l{\"a}-Remes and Aleksandar Radujkovic and Lothar Kanz and Victoria Potter and Patrice Chevallier and Matthias Stelljes and Eefke Petersen and Stephen Robinson and Xavier Poir{\'e} and Evgeny Klyuchnikov and Hern{\'a}ndez-Boluda, {Juan Carlos} and Tomasz Czerw and Patrick Hayden and Nicolaus Kr{\"o}ger and Ibrahim Yakoub-Agha",
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T1 - Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis

T2 - A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

AU - McLornan, Donal

AU - Szydlo, Richard

AU - Koster, Linda

AU - Chalandon, Yves

AU - Robin, Marie

AU - Wolschke, Christine

AU - Beelen, Dietrich

AU - Socié, Gerard

AU - Bornhäuser, Martin

AU - Angelucci, Emanuele

AU - Niederwieser, Dietger

AU - Gerbitz, Arnim

AU - Finke, Jürgen

AU - Vitek, Antonin

AU - Itälä-Remes, Maija

AU - Radujkovic, Aleksandar

AU - Kanz, Lothar

AU - Potter, Victoria

AU - Chevallier, Patrice

AU - Stelljes, Matthias

AU - Petersen, Eefke

AU - Robinson, Stephen

AU - Poiré, Xavier

AU - Klyuchnikov, Evgeny

AU - Hernández-Boluda, Juan Carlos

AU - Czerw, Tomasz

AU - Hayden, Patrick

AU - Kröger, Nicolaus

AU - Yakoub-Agha, Ibrahim

PY - 2019/1/1

Y1 - 2019/1/1

N2 - This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P =.10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P =.08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P =.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P =.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.

AB - This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P =.10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P =.08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P =.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P =.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.

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KW - Myeloproliferative

KW - Reduced intensity

KW - Stem cell transplantation

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