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

Research output: Contribution to journalArticle

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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Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Maintenance Chemotherapy
Drug Therapy
Anthracyclines
Vincristine
Doxorubicin
Cyclophosphamide
Dexamethasone
Monoclonal Antibodies
Rituximab
Survival
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia. / Thomas, Deborah A.; O'Brien, Susan; Faderl, Stefan; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Wierda, William; Ravandi, Farhad; Verstovsek, Srdan; Jorgensen, Jeffrey L.; Bueso-Ramos, Carlos; Andreeff, Michael; Pierce, Sherry; Garris, Rebecca; Keating, Michael J.; Cortes, Jorge; Kantarjian, Hagop M.

In: Journal of Clinical Oncology, Vol. 28, No. 24, 20.08.2010, p. 3880-3889.

Research output: Contribution to journalArticle

Thomas, DA, O'Brien, S, Faderl, S, Garcia-Manero, G, Ferrajoli, A, Wierda, W, Ravandi, F, Verstovsek, S, Jorgensen, JL, Bueso-Ramos, C, Andreeff, M, Pierce, S, Garris, R, Keating, MJ, Cortes, J & Kantarjian, HM 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, vol. 28, no. 24, pp. 3880-3889. https://doi.org/10.1200/JCO.2009.26.9456
Thomas, Deborah A. ; O'Brien, Susan ; Faderl, Stefan ; Garcia-Manero, Guillermo ; Ferrajoli, Alessandra ; Wierda, William ; Ravandi, Farhad ; Verstovsek, Srdan ; Jorgensen, Jeffrey L. ; Bueso-Ramos, Carlos ; Andreeff, Michael ; Pierce, Sherry ; Garris, Rebecca ; Keating, Michael J. ; Cortes, Jorge ; Kantarjian, Hagop M. / Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 24. pp. 3880-3889.
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title = "Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia",
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.",
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T1 - Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome - Negative precursor B-lineage acute lymphoblastic leukemia

AU - Thomas, Deborah A.

AU - O'Brien, Susan

AU - Faderl, Stefan

AU - Garcia-Manero, Guillermo

AU - Ferrajoli, Alessandra

AU - Wierda, William

AU - Ravandi, Farhad

AU - Verstovsek, Srdan

AU - Jorgensen, Jeffrey L.

AU - Bueso-Ramos, Carlos

AU - Andreeff, Michael

AU - Pierce, Sherry

AU - Garris, Rebecca

AU - Keating, Michael J.

AU - Cortes, Jorge

AU - Kantarjian, Hagop M.

PY - 2010/8/20

Y1 - 2010/8/20

N2 - 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.

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