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

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/m(2), 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.

Figure 1

(A) Cumulative incidence of non-relapse mortality of 27% among 372 patients aged 60 years or older, who were treated with nonmyeloablative conditioning and HCT. (B) No statistically significant difference (p=0.81, likelihood ratio statistics from Cox regression model) detected in cumulative incidences of non-relapse mortality among patients aged 60–64 (n=218), 65–69 (n=121), and ≥70 years (n=33).

Figure 2

(A) Rate of disease progression or relapse of 41% among 372 patients aged 60 years or older, who were treated with nonmyeloablative conditioning and HCT. (B) No statistically significant difference (p=0.38, likelihood ratio statistics from Cox regression model) detected in rates of disease progression or relapse among patients aged 60–64 (n=218), 65–69 (n=121), and ≥70 years (n=33).

Figure 3

(A) Kaplan-Meier estimate of overall survival of 35% among 372 patients aged 60 years or older, who were treated with nonmyeloablative conditioning and HCT. (B) No statistically significant difference (p=0.18, likelihood ratio statistics from Cox regression model) detected in rates of overall survival among patients aged 60–64 (n=218), 65–69 (n=121), and ≥70 years (n=33).