Introduction Adult patients with acute lymphoblastic leukemia (ALL) have a poorer outcome than children, characterized by a higher relapse and shorter survival rate. This difference in survival has been par- ticularly highlighted for older adolescents and young adults (AYAs) with ALL with an age range of 16 to 20 years who may end up being treated with either pediatric or adult regimens. 1 A recent study of more than 300 AYAs showed significantly better event- free and overall survival when AYAs received therapy according to pediatric protocols rather than adult programs. 2 There are several factors to explain these results, including social, disease-specific, and treatment-related features. In the aforementioned analysis, a comparison between the regimens showed that the children’s protocols incorporated earlier and more intensive central nervous system (CNS) prophylaxis and higher cumulative doses of the nonmyelosuppressive components such as vincristine, steroids, and asparaginase. Numerous studies have since been reported using such “pediatric-like” protocols in younger adults whereby the upper age limit for these approaches has been extended to 40 years and higher. 3-7 The hyper-CVAD (cyclophosphamide/vincristine/doxorubicin/ dexamethasone) program is a well-established regimen for the treat- ment of adult patients with ALL. 8 Up to 8 cycles of fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine are followed by a prolonged standard maintenance with interspersed cycles of Abstract Augmented Hyper-CVAD Based on Dose- Intensified Vincristine, Dexamethasone, and Asparaginase in Adult Acute Lymphoblastic Leukemia Salvage Therapy Stefan Faderl, Deborah Ann Thomas, Susan O’Brien, Farhad Ravandi, Guillermo Garcia-Manero, Gautam Borthakur, Alessandra Ferrajoli, Srdan Verstovsek, Mohamed Ayoubi, Michael Rytting, Jennie Feliu, Hagop M. Kantarjian The prognosis of adult patients with relapsed acute lymphoblastic leukemia (ALL) remains poor. Recent studies in adoles- cents and young adults reported better outcomes when therapy was intensified. Based on hyper-CVAD (cyclophospha- mide/vincristine/doxorubicin/dexamethasone) as a backbone, we designed an augmented version with intensified doses of vincristine, dexamethasone, and asparaginase (L-asparaginase in the first 62 patients and pegaspargase in the remainder) starting from course 1. Ninety patients have been enrolled, with a median age of 34 years (range, 14-70 years). Most patients (78%) had pre-B ALL and were in first salvage (76%), with a first remission duration of 12.6 months (range, 1-78 months). Ten patients had primary refractory disease. Of 88 evaluable patients, 41 (47%) achieved complete remission (CR), with a median time to CR of 29 days (range, 18-80 days). Eight patients (9%) died within the first 30 days. Median CR dura- tion, progression-free survival, and overall survival were 5, 6.2, and 6 months, respectively. Median overall survival of CR patients was 10.2 months (range, 1.4-69.5+ months). Twenty-eight patients (32%) proceeded to stem cell transplantation. Myelosuppression-associated complications were frequent. Pegaspargase was equally effective and easier to administer than L-asparaginase. Augmented hyper-CVAD may be suitable to be studied in younger adults with untreated ALL. Clinical Lymphoma, Myeloma & Leukemia, Vol. 11, No. 1, 54-59, 2011; DOI: 10.3816/CLML.2011.n.007 Keywords: ALL, Chemotherapy, Myelosuppression, Pegaspargase Original Study Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Submitted: Aug 3, 2010; Revised: Sep 18, 2010; Accepted: Sep 24, 2010 Address for correspondence: Stefan Faderl, MD, Department of Leukemia, Unit 428, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX 77230-1402 Fax: 713-792-9616; e-mail: sfaderl@mdanderson.org 2152-2650/$ - see frontmatter © 2011 Elsevier Inc. All rights reserved. 54 | Clinical Lymphoma, Myeloma & Leukemia February 2011 The summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. For authorization to photocopy items for internal or personal use, visit www.elsevier.com/permissions.