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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. MD, MSc; Sandmaier, Brenda M. MD; Storer, Barry E. PhD; Franke, Georg N. MD; Laport, Ginna G. MD; Chauncey, Thomas R. MD; Agura, Edward MD; Maziarz, Richard T. MD; Langston, Amelia MD; Hari, Parameswaran MD; Pulsipher, Michael A. MD; Bethge, Wolfgang MD; Sahebi, Firoozeh MD; Bruno, Benedetto MD; Maris, Michael B. MD; Yeager, Andrew MD; Petersen, Finn Bo MD; Vindelov, Lars MD, DMsc; McSweeney, Peter A. MD; Hubel, Kai MD; Mielcarek, Marco MD; Georges, George E. MD; Niederwieser, Dietger MD; Blume, Karl G. MD; Maloney, David G. MD, PhD; Storb, Rainer MD
[Article] JAMA. 306(17):1874-1883, November 2, 2011.

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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. Postgrafting immunosuppression 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 < .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.