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Originally published as JCO Early Release 10.1200/JCO.2008.18.6916 on January 5 2009 Publisher’s Note The February 20, 2009, article by Huguet et al, entitled, “Pediatric–Inspired Therapy in Adults With Philadelphia Chromosome—Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 Study” (J Clin Oncol 27:911–918, 2009), was published in print with errors in Table 1. This article was also published online on January 5, 2009, with errors in Table 1. Under “Remission induction,” the term “corticosteroid prophase” was given, whereas it should have been “corticosteroid prephase.” The dose for L–asparaginase was given as, “6,000 U/m2/d on days 8, 10, 12, 18, 20, 22, 24, and 26,” and it should have been, “6,000 U/m2/d on days 8, 10, 12, 20, 22, 24, 26, and 28.” Also, the dose for cyclophosphamide (CPM) was given as, “750 mg/m2/d on days 1 and 8; 750 mg/m2 on day 15 in good early responders; 500 mg/m2/12 h on days 15 and 16 in poor early responders,” and should have been, “750 mg/m2/d on day 1; 750 mg/m2/d on day 15 in good early responders; 500 mg/m2/12 h on days 15 and 16 in poor early responders.” Under “Consolidation blocks 3, 6, and 9,” the dose for CPM was given as, “500 mg/m2 on days 29 and 30,” and should have been, “500 mg/m2/d on days 29 and 30.” Also, the dose for VP–16 was given as, “75 mg/m2m/d on days 29 and 30,“ and should have been, “75 mg/m2/d on days 29 and 30.” Under “Late intensification (between consolidation blocks 6 and 7),” the dose for lenograstim was not indicated for patients in complete remission after the first induction course, and should have been, “150 μg/m2/d if neutrophils < 0.5 G/L to myeloid recovery.” Under “Maintenance therapy,” the dose for prednisone (PDN) was given as, “40 mg/m2/d on days 1–14 monthly for 12 months,” and should have been, “40 mg/m2/d on days 1–7 monthly for 12 months.” Under “CNS therapy, Treatment of patients with initial CNS involvement,” the dose for triple IT injections was given as, “Eight between days 7 and 21 of induction; four during the first two consolidation blocks; one at day 29 of consolidation blocks 3 and 6,” and should have been, “Eight between days –7 and 21 of induction; four during the first two consolidation blocks; one at day 29 of consolidation blocks 3 and 6.” Also, the dose for cranial irradiation was given as, “15 Gy before SCT or 18 Gy before late intensification; 6–MP 60 mg/m2/d during irradiation,” and should have been, “15 Gy before SCT or 24 Gy before maintenance therapy initiation; 6–MP 60 mg/m2/d during irradiation.” Also under “CNS therapy,” the footnote for triple IT injections was given as: †Triple IT injections consisted of MTX 15 mg, Ara–C 40 mg, and PDN 40 mg. While it should have been: †Triple IT injections consisted of MTX 15 mg, Ara-C 40 mg, and methylprednisolone 40 mg. These corrections have been made online as of May 12, 2009. These corrections are not reflected in the February 20, 2009, print edition. An erratum for the print edition was published in the May 20, 2009, issue (J Clin Oncol 27:2574, 2009). © 2009 American Society of Clinical Oncology.
Pediatric-Inspired Therapy in Adults With Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia: The GRAALL-2003 StudyFrom the Departments of Hematology, Hôpital Purpan, Toulouse; Hôpital Haut-Lévèque, Bordeaux; Hôpital Saint-Louis, Hôpital Necker, and Hôpital Pitié-Salpêtriere, Assistance Publique–Hôpitaux de Paris, Paris; Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon; Hotel Dieu, Nantes; Hôpital de la Timone, Marseille; Hôpital Larrey, Angers; Hôpital Brabois, Nancy, France; Hôpital Universitaire, Geneva, Switzerland; and Cliniques Universitaires Saint-Luc, Brussels, Belgium. Corresponding author: Hervé Dombret, MD, Department of Hematology, Hôpital Saint-Louis, 1 Ave Claude Vellefaux, 75010 Paris, France; e-mail: herve.dombret{at}sls.aphp.fr. Purpose Retrospective comparisons have suggested that adolescents or teenagers with acute lymphoblastic leukemia (ALL) benefit from pediatric rather than adult chemotherapy regimens. Thus, the aim of the present phase II study was to test a pediatric-inspired treatment, including intensified doses of nonmyelotoxic drugs, such as prednisone, vincristine, or L-asparaginase, in adult patients with ALL up to the age of 60 years. Patients and Methods Between 2003 and 2005, 225 adult patients (median age, 31 years; range, 15 to 60 years) with Philadelphia chromosome–negative ALL were enrolled onto the Group for Research on Adult Acute Lymphoblastic Leukemia 2003 protocol, which included several pediatric options. Some adult options, such as allogeneic stem-cell transplantation for patients with high-risk ALL, were nevertheless retained. Results were retrospectively compared with the historical France-Belgium Group for Lymphoblastic Acute Leukemia in Adults 94 (LALA-94) trial experience in 712 patients age 15 to 55 years. Results Complete remission rate was 93.5%. At 42 months, event-free survival (EFS) and overall survival (OS) rates were 55% (95% CI, 48% to 52%) and 60% (95% CI, 53% to 66%), respectively. Age remained an important bad prognostic factor, with 45 years of age as best cutoff. In older versus younger patients, there was a higher cumulative incidence of chemotherapy-related deaths (23% v 5%, respectively; P < .001) and deaths in first CR (22% v 5%, respectively; P < .001), whereas the incidence of relapse remained stable (30% v 32%, respectively). Complete remission rate (P = .02), EFS (P < .001), and OS (P < .001) compared favorably with the previous LALA-94 experience. Conclusion These results suggest that pediatric-inspired therapy markedly improves the outcome of adult patients with ALL, at least until the age of 45 years. Written on behalf of the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). GRAALL includes the former France-Belgium Group for Lymphoblastic Acute Leukemia in Adults, the French Western-Eastern Group for Lymphoblastic Acute Leukemia, and the Swiss Group for Clinical Cancer Research. GRAALL participating centers and investigators are listed in the Appendix. Supported by the Regional Clinical Research Office, Toulouse, France, and by grants from the Programme Hospitalier de Recherche Clinique (PHRC ID No. 0200701) in France and the Swiss Federal Government in Switzerland. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. Clinical Trials repository link available on JCO.org.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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