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Effect of Age and Previous Autologous Transplantation on Nonrelapse Mortality and Survival in Patients Treated With Reduced-Intensity Conditioning and Allografting for Advanced Hematologic Malignancies

From the Divisione di Ematologia and Ufficio Operativo, Istituto Nazionale Tumori, Università di Milano; Divisione di Ematologia, Unità Trapianto Midollo, Ospedale San Raffaele, Milano; Divisione di Ematologia II, Ospedale San Martino, Genova; Divisione di Ematologia, Università di Ancona, Ancona; Divisione di Ematologia, Università di Udine, Udine; Divisione di Ematologia, Ospedale Riuniti, Bergamo; Unità Trapianto Midollo, Ospedale Cervello, Palermo; Divisione di Ematologia, Ospedale San Camillo-Forlanini, Roma; Istituto di Ematologia–Oncologia, Università di Bologna, Bologna; and Divisione di Ematologia, Università di Torino, Torino, Italy

Address reprint requests to Paolo Corradini, MD, Division of Hematology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; e-mail: paolo.corradini{at}istitutotumori.mi.it

PURPOSE: Older age and a previously failed autologous stem-cell transplantation (SCT) are poor prognostic factors for patients receiving myeloablative conditioning and allogeneic SCT. Reduced-intensity conditioning (RIC) regimens achieved a significant reduction of treatment-related mortality, but the influence of previously described risk factors on the outcome of this novel transplantation strategy have not been fully analyzed yet.

PATIENTS AND METHODS: One hundred fifty patients with advanced hematologic malignancies received a RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/m²), and cyclophosphamide (60 mg/kg), followed by an allogeneic transplantation from an HLA-identical sibling donor. Patients were divided into two cohorts according to age; 90 patients were younger than 55 years, and 60 patients were 55 years old or older. The other pretransplantation characteristics were fairly balanced.

RESULTS: Actuarial 5-year nonrelapse mortality (NRM) rate was not statistically different between the groups (13% in the younger group and 19% in the older group). By univariate and multivariate analysis, NRM was significantly higher in older patients who previously experienced failure with an autograft. The occurrence of grade 3 to 4 acute graft-versus-host disease (GVHD) or extensive chronic GVHD was associated with a higher NRM in both age cohorts. Overall survival (OS) was not statistically different between the younger (66%) and older groups (61%). By multivariate analysis, refractory disease was associated with a worse OS irrespective of age group.

CONCLUSION: RIC transplantations show a rather low NRM, and age 55 years per se cannot be considered a risk factor anymore. The timing of transplantation and novel strategies for the prevention of severe GVHD could further improve patient outcome.

Supported in part by the Italian Association for Cancer Research, and Compagnia di San Paolo "Programma Oncologia."

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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