The use of immunosuppressive therapy in MDS: Clinical outcomes and their predictors in a large international patient cohort

Maximilian Stahl, Michelle DeVeaux, Theo De Witte, Judith Neukirchen, Mikkael A. Sekeres, Andrew M. Brunner, Gail J. Roboz, David P. Steensma, Vijaya R. Bhatt, Uwe Platzbecker, Thomas Cluzeau, Pedro H. Prata, Raphaël Itzykson, Pierre Fenaux, Amir T. Fathi, Alexandra Smith, Ulrich Germing, Ellen K. Ritchie, Vivek Verma, Aziz NazhaJaroslaw P. Maciejewski, Nikolai A. Podoltsev, Thomas Prebet, Valeria Santini, Steven D. Gore, Rami S. Komrokji, Amer M. Zeidan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST.We examined outcomes associated with IST and predictors of benefit in a large international cohort of patientswith MDS. Datawere collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006MDS InternationalWorking Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios forOS.Weidentified 207patientswithMDSreceiving IST, excluding steroidmonotherapy. Themost common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%)who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow(cellularity, 20%); horse ATG plus cyclosporinewas more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.

Original languageEnglish (US)
Pages (from-to)1765-1772
Number of pages8
JournalBlood Advances
Volume2
Issue number14
DOIs
StatePublished - Jul 24 2018

Fingerprint

Myelodysplastic Syndromes
Immunosuppressive Agents
Erythrocyte Transfusion
Antilymphocyte Serum
Confidence Intervals
Therapeutics
Logistic Models
Bone Marrow
Paroxysmal Hemoglobinuria
Survival
Prednisone
Proportional Hazards Models
Cyclosporine
Horses
Clone Cells
Lymphocytes
Rabbits

ASJC Scopus subject areas

  • Hematology

Cite this

Stahl, M., DeVeaux, M., De Witte, T., Neukirchen, J., Sekeres, M. A., Brunner, A. M., ... Zeidan, A. M. (2018). The use of immunosuppressive therapy in MDS: Clinical outcomes and their predictors in a large international patient cohort. Blood Advances, 2(14), 1765-1772. https://doi.org/10.1182/bloodadvances.2018019414

The use of immunosuppressive therapy in MDS : Clinical outcomes and their predictors in a large international patient cohort. / Stahl, Maximilian; DeVeaux, Michelle; De Witte, Theo; Neukirchen, Judith; Sekeres, Mikkael A.; Brunner, Andrew M.; Roboz, Gail J.; Steensma, David P.; Bhatt, Vijaya R.; Platzbecker, Uwe; Cluzeau, Thomas; Prata, Pedro H.; Itzykson, Raphaël; Fenaux, Pierre; Fathi, Amir T.; Smith, Alexandra; Germing, Ulrich; Ritchie, Ellen K.; Verma, Vivek; Nazha, Aziz; Maciejewski, Jaroslaw P.; Podoltsev, Nikolai A.; Prebet, Thomas; Santini, Valeria; Gore, Steven D.; Komrokji, Rami S.; Zeidan, Amer M.

In: Blood Advances, Vol. 2, No. 14, 24.07.2018, p. 1765-1772.

Research output: Contribution to journalArticle

Stahl, M, DeVeaux, M, De Witte, T, Neukirchen, J, Sekeres, MA, Brunner, AM, Roboz, GJ, Steensma, DP, Bhatt, VR, Platzbecker, U, Cluzeau, T, Prata, PH, Itzykson, R, Fenaux, P, Fathi, AT, Smith, A, Germing, U, Ritchie, EK, Verma, V, Nazha, A, Maciejewski, JP, Podoltsev, NA, Prebet, T, Santini, V, Gore, SD, Komrokji, RS & Zeidan, AM 2018, 'The use of immunosuppressive therapy in MDS: Clinical outcomes and their predictors in a large international patient cohort', Blood Advances, vol. 2, no. 14, pp. 1765-1772. https://doi.org/10.1182/bloodadvances.2018019414
Stahl, Maximilian ; DeVeaux, Michelle ; De Witte, Theo ; Neukirchen, Judith ; Sekeres, Mikkael A. ; Brunner, Andrew M. ; Roboz, Gail J. ; Steensma, David P. ; Bhatt, Vijaya R. ; Platzbecker, Uwe ; Cluzeau, Thomas ; Prata, Pedro H. ; Itzykson, Raphaël ; Fenaux, Pierre ; Fathi, Amir T. ; Smith, Alexandra ; Germing, Ulrich ; Ritchie, Ellen K. ; Verma, Vivek ; Nazha, Aziz ; Maciejewski, Jaroslaw P. ; Podoltsev, Nikolai A. ; Prebet, Thomas ; Santini, Valeria ; Gore, Steven D. ; Komrokji, Rami S. ; Zeidan, Amer M. / The use of immunosuppressive therapy in MDS : Clinical outcomes and their predictors in a large international patient cohort. In: Blood Advances. 2018 ; Vol. 2, No. 14. pp. 1765-1772.
@article{b47addfe97cb48fba156abeb564ec379,
title = "The use of immunosuppressive therapy in MDS: Clinical outcomes and their predictors in a large international patient cohort",
abstract = "Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST.We examined outcomes associated with IST and predictors of benefit in a large international cohort of patientswith MDS. Datawere collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006MDS InternationalWorking Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios forOS.Weidentified 207patientswithMDSreceiving IST, excluding steroidmonotherapy. Themost common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43{\%}). Overall response rate (ORR) was 48.8{\%}, including 11.2{\%} (95{\%} confidence interval [CI], 6.5{\%}-18.4{\%})who achieved a complete remission and 30{\%} (95{\%} CI, 22.3{\%}-39.5{\%}) who achieved RBC TI. Median OS was 47.4 months (95{\%} CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow(cellularity, 20{\%}); horse ATG plus cyclosporinewas more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.",
author = "Maximilian Stahl and Michelle DeVeaux and {De Witte}, Theo and Judith Neukirchen and Sekeres, {Mikkael A.} and Brunner, {Andrew M.} and Roboz, {Gail J.} and Steensma, {David P.} and Bhatt, {Vijaya R.} and Uwe Platzbecker and Thomas Cluzeau and Prata, {Pedro H.} and Rapha{\"e}l Itzykson and Pierre Fenaux and Fathi, {Amir T.} and Alexandra Smith and Ulrich Germing and Ritchie, {Ellen K.} and Vivek Verma and Aziz Nazha and Maciejewski, {Jaroslaw P.} and Podoltsev, {Nikolai A.} and Thomas Prebet and Valeria Santini and Gore, {Steven D.} and Komrokji, {Rami S.} and Zeidan, {Amer M.}",
year = "2018",
month = "7",
day = "24",
doi = "10.1182/bloodadvances.2018019414",
language = "English (US)",
volume = "2",
pages = "1765--1772",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "14",

}

TY - JOUR

T1 - The use of immunosuppressive therapy in MDS

T2 - Clinical outcomes and their predictors in a large international patient cohort

AU - Stahl, Maximilian

AU - DeVeaux, Michelle

AU - De Witte, Theo

AU - Neukirchen, Judith

AU - Sekeres, Mikkael A.

AU - Brunner, Andrew M.

AU - Roboz, Gail J.

AU - Steensma, David P.

AU - Bhatt, Vijaya R.

AU - Platzbecker, Uwe

AU - Cluzeau, Thomas

AU - Prata, Pedro H.

AU - Itzykson, Raphaël

AU - Fenaux, Pierre

AU - Fathi, Amir T.

AU - Smith, Alexandra

AU - Germing, Ulrich

AU - Ritchie, Ellen K.

AU - Verma, Vivek

AU - Nazha, Aziz

AU - Maciejewski, Jaroslaw P.

AU - Podoltsev, Nikolai A.

AU - Prebet, Thomas

AU - Santini, Valeria

AU - Gore, Steven D.

AU - Komrokji, Rami S.

AU - Zeidan, Amer M.

PY - 2018/7/24

Y1 - 2018/7/24

N2 - Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST.We examined outcomes associated with IST and predictors of benefit in a large international cohort of patientswith MDS. Datawere collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006MDS InternationalWorking Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios forOS.Weidentified 207patientswithMDSreceiving IST, excluding steroidmonotherapy. Themost common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%)who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow(cellularity, 20%); horse ATG plus cyclosporinewas more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.

AB - Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST.We examined outcomes associated with IST and predictors of benefit in a large international cohort of patientswith MDS. Datawere collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006MDS InternationalWorking Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios forOS.Weidentified 207patientswithMDSreceiving IST, excluding steroidmonotherapy. Themost common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%)who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow(cellularity, 20%); horse ATG plus cyclosporinewas more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows.

UR - http://www.scopus.com/inward/record.url?scp=85072746246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072746246&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2018019414

DO - 10.1182/bloodadvances.2018019414

M3 - Article

C2 - 30037803

AN - SCOPUS:85072746246

VL - 2

SP - 1765

EP - 1772

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 14

ER -