Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

Rainer Storb, Boglarka Gyurkocza, Barry E. Storer, Mohamed L. Sorror, Karl Blume, Dietger Niederwieser, Thomas R. Chauncey, Michael A. Pulsipher, Finn B. Petersen, Firoozeh Sahebi, Edward D. Agura, Parameswaran Hari, Benedetto Bruno, Peter A. McSweeney, Michael B. Maris, Richard T. Maziarz, Amelia A. Langston, Wolfgang Bethge, Lars Vindeloøv, Georg Nikolaus FrankeGinna G. Laport, Andrew M Yeager, Kai Hübel, H. Joachim Deeg, George E. Georges, Mary E D Flowers, Paul J. Martin, Marco Mielcarek, Ann E. Woolfrey, David G. Maloney, Brenda M. Sandmaier

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graftversus- host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.

Original languageEnglish (US)
Pages (from-to)1530-1538
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number12
DOIs
StatePublished - Apr 20 2013

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Cell Transplantation
Graft vs Host Disease
Transplants
Neoplasms
Comorbidity
Mortality
Mycophenolic Acid
Recurrence
Unrelated Donors
Whole-Body Irradiation
Acute Disease
Hematologic Neoplasms
Immune System
Tissue Donors
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Storb, R., Gyurkocza, B., Storer, B. E., Sorror, M. L., Blume, K., Niederwieser, D., ... Sandmaier, B. M. (2013). Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. Journal of Clinical Oncology, 31(12), 1530-1538. https://doi.org/10.1200/JCO.2012.45.0247

Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. / Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E.; Sorror, Mohamed L.; Blume, Karl; Niederwieser, Dietger; Chauncey, Thomas R.; Pulsipher, Michael A.; Petersen, Finn B.; Sahebi, Firoozeh; Agura, Edward D.; Hari, Parameswaran; Bruno, Benedetto; McSweeney, Peter A.; Maris, Michael B.; Maziarz, Richard T.; Langston, Amelia A.; Bethge, Wolfgang; Vindeloøv, Lars; Franke, Georg Nikolaus; Laport, Ginna G.; Yeager, Andrew M; Hübel, Kai; Deeg, H. Joachim; Georges, George E.; Flowers, Mary E D; Martin, Paul J.; Mielcarek, Marco; Woolfrey, Ann E.; Maloney, David G.; Sandmaier, Brenda M.

In: Journal of Clinical Oncology, Vol. 31, No. 12, 20.04.2013, p. 1530-1538.

Research output: Contribution to journalArticle

Storb, R, Gyurkocza, B, Storer, BE, Sorror, ML, Blume, K, Niederwieser, D, Chauncey, TR, Pulsipher, MA, Petersen, FB, Sahebi, F, Agura, ED, Hari, P, Bruno, B, McSweeney, PA, Maris, MB, Maziarz, RT, Langston, AA, Bethge, W, Vindeloøv, L, Franke, GN, Laport, GG, Yeager, AM, Hübel, K, Deeg, HJ, Georges, GE, Flowers, MED, Martin, PJ, Mielcarek, M, Woolfrey, AE, Maloney, DG & Sandmaier, BM 2013, 'Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation', Journal of Clinical Oncology, vol. 31, no. 12, pp. 1530-1538. https://doi.org/10.1200/JCO.2012.45.0247
Storb, Rainer ; Gyurkocza, Boglarka ; Storer, Barry E. ; Sorror, Mohamed L. ; Blume, Karl ; Niederwieser, Dietger ; Chauncey, Thomas R. ; Pulsipher, Michael A. ; Petersen, Finn B. ; Sahebi, Firoozeh ; Agura, Edward D. ; Hari, Parameswaran ; Bruno, Benedetto ; McSweeney, Peter A. ; Maris, Michael B. ; Maziarz, Richard T. ; Langston, Amelia A. ; Bethge, Wolfgang ; Vindeloøv, Lars ; Franke, Georg Nikolaus ; Laport, Ginna G. ; Yeager, Andrew M ; Hübel, Kai ; Deeg, H. Joachim ; Georges, George E. ; Flowers, Mary E D ; Martin, Paul J. ; Mielcarek, Marco ; Woolfrey, Ann E. ; Maloney, David G. ; Sandmaier, Brenda M. / Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 12. pp. 1530-1538.
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abstract = "Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graftversus- host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45{\%} to 75{\%} of patients, and 5-year survival ranged from 25{\%} to 60{\%}. At 5 years, the nonrelapse mortality (NRM) rate was 24{\%}, and the relapse mortality rate was 34.5{\%}. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.",
author = "Rainer Storb and Boglarka Gyurkocza and Storer, {Barry E.} and Sorror, {Mohamed L.} and Karl Blume and Dietger Niederwieser and Chauncey, {Thomas R.} and Pulsipher, {Michael A.} and Petersen, {Finn B.} and Firoozeh Sahebi and Agura, {Edward D.} and Parameswaran Hari and Benedetto Bruno and McSweeney, {Peter A.} and Maris, {Michael B.} and Maziarz, {Richard T.} and Langston, {Amelia A.} and Wolfgang Bethge and Lars Vindelo{\o}v and Franke, {Georg Nikolaus} and Laport, {Ginna G.} and Yeager, {Andrew M} and Kai H{\"u}bel and Deeg, {H. Joachim} and Georges, {George E.} and Flowers, {Mary E D} and Martin, {Paul J.} and Marco Mielcarek and Woolfrey, {Ann E.} and Maloney, {David G.} and Sandmaier, {Brenda M.}",
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TY - JOUR

T1 - Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

AU - Storb, Rainer

AU - Gyurkocza, Boglarka

AU - Storer, Barry E.

AU - Sorror, Mohamed L.

AU - Blume, Karl

AU - Niederwieser, Dietger

AU - Chauncey, Thomas R.

AU - Pulsipher, Michael A.

AU - Petersen, Finn B.

AU - Sahebi, Firoozeh

AU - Agura, Edward D.

AU - Hari, Parameswaran

AU - Bruno, Benedetto

AU - McSweeney, Peter A.

AU - Maris, Michael B.

AU - Maziarz, Richard T.

AU - Langston, Amelia A.

AU - Bethge, Wolfgang

AU - Vindeloøv, Lars

AU - Franke, Georg Nikolaus

AU - Laport, Ginna G.

AU - Yeager, Andrew M

AU - Hübel, Kai

AU - Deeg, H. Joachim

AU - Georges, George E.

AU - Flowers, Mary E D

AU - Martin, Paul J.

AU - Mielcarek, Marco

AU - Woolfrey, Ann E.

AU - Maloney, David G.

AU - Sandmaier, Brenda M.

PY - 2013/4/20

Y1 - 2013/4/20

N2 - Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graftversus- host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.

AB - Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graftversus- host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.

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U2 - 10.1200/JCO.2012.45.0247

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