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Blood, 15 January 2004, Vol. 103, No. 2, pp. 435-441.
Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-07-2236.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors
Didier Blaise,
Jacques Olivier Bay,
Catherine Faucher,
Mauricette Michallet,
Jean-Michel Boiron,
Bachra Choufi,
Jean-Yves Cahn,
Nicole Gratecos,
Jean-Jacques Sotto,
Sylvie François,
Joel Fleury,
Mohamad Mohty,
Christian Chabannon,
Karin Bilger,
Gwenaelle Gravis,
Frédéric Viret,
Anne Chantal Braud,
Valérie Jeanne Bardou,
Dominique Maraninchi, and
Patrice Viens
From the Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France; Université de la Méditerranée, Marseille, France; Centre d'Investigation clinique, Hôpital Ste Marguerite, Marseille, France; Centre Jean Perrin, Clermont Ferrand, France; Centre Hospitalier Universitaire (CHU) Edouard Herriot, Lyon, France; CHU Haut Lévèque, Bordeaux, France; CHU Jean Minjoz, Besançon, France; CHU Cimiez, Nice, France; CHU Michalon, Grenoble, France; CHU Angers, Angers, France; Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France; and Unité de Biostatistiques, Institut Paoli-Calmettes, Marseille, France.
In this prospective multicenter program, we investigated allogeneic stem cell transplantation (ASCT) from HLA-identical siblings following reduced-intensity conditioning (RIC) regimen for patients with refractory metastatic solid tumors (STs). Fifty-seven patients, of whom 39 had a progressive disease (PD) at time of ASCT, received an RIC ASCT combining fludarabine, antithymocyte globulin (ATG), and busulfan. Patients were analyzed in terms of engraftment, transplant-related mortality (TRM), disease response, and outcome. In this setting, RIC was associated with rapid engraftment and low overall TRM (9% [95% confidence interval (CI), 1%-16%]). The cumulative incidence of objective responses (ORs) reached 14% (95% CI, 6%-30%) with this being significantly higher in patients without PD (44% [95% CI, 21%-67%] versus 0; P < .0001) at time of ASCT. Achievement of OR translated into a significantly better overall survival (OS). In multivariate analysis, OS was significantly influenced by disease status at time of ASCT (odds ratio, 4.88; P < .001) and chronic graft-versus-host disease (GVHD) occurrence (odds ratio, 2.86; P < .01). Overall, these results showed that OR can occur after RIC ASCT for resistant ST with a relatively low TRM and potential benefit especially in patients with slowly progressive disease. Further studies are warranted in patients with less advanced ST.
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