Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia

Deborah A. Thomas, Susan O'Brien, Stefan Faderl, Guillermo Garcia-Manero, Alessandra Ferrajoli, William Wierda, Farhad Ravandi, Srdan Verstovsek, Jeffrey L. Jorgensen, Carlos Bueso-Ramos, Michael Andreeff, Sherry Pierce, Rebecca Garris, Michael J. Keating, Jorge Cortes, Hagop M. Kantarjian

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235 Scopus citations

Abstract

Purpose: The adverse prognosis of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia (ALL) prompted incorporation of monoclonal antibody therapy with rituximab into the intensive chemotherapy regimen hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone). Other modifications (irrespective of CD20 expression) included early anthracycline intensification, alterations in number of risk-adapted intrathecal chemotherapy treatments for CNS prophylaxis, additional early and late intensifications, and extension of maintenance phase chemotherapy by 6 months. Patients and Methods: Two hundred eighty-two adolescents and adults with de novo Philadelphia chromosome (Ph) - negative precursor B-lineage ALL were treated with standard or modified hyper-CVAD regimens. The latter incorporated standard-dose rituximab if CD20 expression ≥20%. Results: The complete remission (CR) rate was 95% with 3-year rates of CR duration (CRD) and survival (OS) of 60% and 50%, respectively. In the younger (age < 60 years) CD20-positive subset, rates of CRD and OS were superior with the modified hyper-CVAD and rituximab regimens compared with standard hyper-CVAD (70% v 38%; P < .001% and 75% v 47%, P = .003). In contrast, rates of CRD and OS for CD20-negative counterparts treated with modified versus standard hyper-CVAD regimens were similar (72% v 68%, P = not significant [NS] and 64% v 65%, P = NS, respectively). Older patients with CD20-positive ALL did not benefit from rituximab-based chemoimmunotherapy (rates of CRD 45% v 50%, P = NS and OS 28% v 32%, P = NS, respectively), related in part to deaths in CR. Conclusion: The incorporation of rituximab into the hyper-CVAD regimen appears to improve outcome for younger patients with CD20-positive Ph-negative precursor B-lineage ALL.

Original languageEnglish (US)
Pages (from-to)3880-3889
Number of pages10
JournalJournal of Clinical Oncology
Volume28
Issue number24
DOIs
StatePublished - Aug 20 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Thomas, D. A., O'Brien, S., Faderl, S., Garcia-Manero, G., Ferrajoli, A., Wierda, W., Ravandi, F., Verstovsek, S., Jorgensen, J. L., Bueso-Ramos, C., Andreeff, M., Pierce, S., Garris, R., Keating, M. J., Cortes, J., & Kantarjian, H. M. (2010). Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia. Journal of Clinical Oncology, 28(24), 3880-3889. https://doi.org/10.1200/JCO.2009.26.9456