Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

Mohamed L. Sorror, Brenda M. Sandmaier, Barry E. Storer, Georg N. Franke, Ginna G. Laport, Thomas R. Chauncey, Edward Agura, Richard Maziarz, Amelia Langston, Parameswaran Hari, Michael A. Pulsipher, Wolfgang Bethge, Firoozeh Sahebi, Benedetto Bruno, Michael B. Maris, Andrew Yeager, Finn Bo Petersen, Lars Vindeløv, Peter A. McSweeney, Kai HübelMarco Mielcarek, George E. Georges, Dietger Niederwieser, Karl G. Blume, David G. Maloney, Rainer Storb

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Context: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. Objective: To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. Design, Setting, and Participants: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m2, before related (n=184) or unrelated (n=188) donor transplants. Postgraftingimmunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures: Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Results: Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P=.003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P≲λτ∀.001 overall). Conclusion: Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.

Original languageEnglish (US)
Pages (from-to)1874-1883
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume306
Issue number17
DOIs
StatePublished - Nov 2 2011

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Cell Transplantation
Hematologic Neoplasms
Recurrence
Disease-Free Survival
Poisons
Graft vs Host Disease
Comorbidity
Odds Ratio
Tissue Donors
Mycophenolic Acid
Chimerism
Survival
Mortality
Whole-Body Irradiation
Incidence
Proportional Hazards Models
Conditioning (Psychology)
Age Groups
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

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Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. / Sorror, Mohamed L.; Sandmaier, Brenda M.; Storer, Barry E.; Franke, Georg N.; Laport, Ginna G.; Chauncey, Thomas R.; Agura, Edward; Maziarz, Richard; Langston, Amelia; Hari, Parameswaran; Pulsipher, Michael A.; Bethge, Wolfgang; Sahebi, Firoozeh; Bruno, Benedetto; Maris, Michael B.; Yeager, Andrew; Petersen, Finn Bo; Vindeløv, Lars; McSweeney, Peter A.; Hübel, Kai; Mielcarek, Marco; Georges, George E.; Niederwieser, Dietger; Blume, Karl G.; Maloney, David G.; Storb, Rainer.

In: JAMA - Journal of the American Medical Association, Vol. 306, No. 17, 02.11.2011, p. 1874-1883.

Research output: Contribution to journalArticle

Sorror, ML, Sandmaier, BM, Storer, BE, Franke, GN, Laport, GG, Chauncey, TR, Agura, E, Maziarz, R, Langston, A, Hari, P, Pulsipher, MA, Bethge, W, Sahebi, F, Bruno, B, Maris, MB, Yeager, A, Petersen, FB, Vindeløv, L, McSweeney, PA, Hübel, K, Mielcarek, M, Georges, GE, Niederwieser, D, Blume, KG, Maloney, DG & Storb, R 2011, 'Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies', JAMA - Journal of the American Medical Association, vol. 306, no. 17, pp. 1874-1883. https://doi.org/10.1001/jama.2011.1558
Sorror, Mohamed L. ; Sandmaier, Brenda M. ; Storer, Barry E. ; Franke, Georg N. ; Laport, Ginna G. ; Chauncey, Thomas R. ; Agura, Edward ; Maziarz, Richard ; Langston, Amelia ; Hari, Parameswaran ; Pulsipher, Michael A. ; Bethge, Wolfgang ; Sahebi, Firoozeh ; Bruno, Benedetto ; Maris, Michael B. ; Yeager, Andrew ; Petersen, Finn Bo ; Vindeløv, Lars ; McSweeney, Peter A. ; Hübel, Kai ; Mielcarek, Marco ; Georges, George E. ; Niederwieser, Dietger ; Blume, Karl G. ; Maloney, David G. ; Storb, Rainer. / Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. In: JAMA - Journal of the American Medical Association. 2011 ; Vol. 306, No. 17. pp. 1874-1883.
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abstract = "Context: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. Objective: To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. Design, Setting, and Participants: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m2, before related (n=184) or unrelated (n=188) donor transplants. Postgraftingimmunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures: Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Results: Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27{\%} (95{\%} CI, 22{\%}-32{\%}) and 41{\%} (95{\%} CI, 36{\%}-46{\%}), respectively, leading to 5-year overall and progression-free survival of 35{\%} (95{\%} CI, 30{\%}-40{\%}) and 32{\%} (95{\%} CI, 27{\%}-37{\%}), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95{\%} CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95{\%} CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P=.003 overall). Similarly, standard relapse risk (HR, 1.67 [95{\%} CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95{\%} CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P≲λτ∀.001 overall). Conclusion: Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35{\%} and 32{\%}, respectively.",
author = "Sorror, {Mohamed L.} and Sandmaier, {Brenda M.} and Storer, {Barry E.} and Franke, {Georg N.} and Laport, {Ginna G.} and Chauncey, {Thomas R.} and Edward Agura and Richard Maziarz and Amelia Langston and Parameswaran Hari and Pulsipher, {Michael A.} and Wolfgang Bethge and Firoozeh Sahebi and Benedetto Bruno and Maris, {Michael B.} and Andrew Yeager and Petersen, {Finn Bo} and Lars Vindel{\o}v and McSweeney, {Peter A.} and Kai H{\"u}bel and Marco Mielcarek and Georges, {George E.} and Dietger Niederwieser and Blume, {Karl G.} and Maloney, {David G.} and Rainer Storb",
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TY - JOUR

T1 - Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

AU - Sorror, Mohamed L.

AU - Sandmaier, Brenda M.

AU - Storer, Barry E.

AU - Franke, Georg N.

AU - Laport, Ginna G.

AU - Chauncey, Thomas R.

AU - Agura, Edward

AU - Maziarz, Richard

AU - Langston, Amelia

AU - Hari, Parameswaran

AU - Pulsipher, Michael A.

AU - Bethge, Wolfgang

AU - Sahebi, Firoozeh

AU - Bruno, Benedetto

AU - Maris, Michael B.

AU - Yeager, Andrew

AU - Petersen, Finn Bo

AU - Vindeløv, Lars

AU - McSweeney, Peter A.

AU - Hübel, Kai

AU - Mielcarek, Marco

AU - Georges, George E.

AU - Niederwieser, Dietger

AU - Blume, Karl G.

AU - Maloney, David G.

AU - Storb, Rainer

PY - 2011/11/2

Y1 - 2011/11/2

N2 - Context: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. Objective: To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. Design, Setting, and Participants: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m2, before related (n=184) or unrelated (n=188) donor transplants. Postgraftingimmunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures: Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Results: Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P=.003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P≲λτ∀.001 overall). Conclusion: Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.

AB - Context: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. Objective: To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. Design, Setting, and Participants: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m2, before related (n=184) or unrelated (n=188) donor transplants. Postgraftingimmunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures: Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. Results: Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT-specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P=.003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P≲λτ∀.001 overall). Conclusion: Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively.

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