|
|
Blood, 15 January 2007, Vol. 109, No. 2, pp. 405-411.
Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-07-033274.
Previous Article | Next Article 
Submitted July 12, 2006
Accepted August 22, 2006
Combination chemoimmunotherapy with pentostatin,
cyclophosphamide and rituximab shows significant
clinical activity with low accompanying toxicity in
previously untreated B-chronic lymphocytic leukemia
Neil E. Kay*, Susan M Geyer, Timothy G. Call, Tait D. Shanafelt, Clive S Zent, Diane F. Jelinek, Renee Tschumper, Nancy D Bone, Gordon W Dewald, Thomas S Lin, Nyla A Heerema, Lisa Smith, Michael R Grever, and John C. Byrd
Mayo Clinic, Rochester, MN
Ohio State University, Columbus, OH
* Corresponding author; email: kay.neil{at}mayo.edu.
Building on the prior work of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2) and rituximab (375 mg/m2) for symptomatic, previously untreated patients (n=65). Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy chain variable region gene, 34% were CD38+ and 34% were ZAP-70+. Thirty patients (52%) had one FISH anomaly, and 21 (36%) had complex FISH defects. 38 patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs, and no major infections. Responses occurred in 58 (91%) with 26 (41%) complete responses (CR), 14 (22%) nodular partial responses (nodular PR), and 18 (28%) partial responses (PR)patients. Many patients with CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del (17p). In contrast, we found this regimen was equally effective in young vs. elderly (>70 yrs) patients and in del(11)(q22.3) vs. other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide and rituximab for previously untreated CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. R. Friedman, J. B. Weinberg, W. T. Barry, B. K. Goodman, A. D. Volkheimer, K. M. Bond, Y. Chen, N. Jiang, J. O. Moore, J. P. Gockerman, et al.
A Genomic Approach to Improve Prognosis and Predict Therapeutic Response in Chronic Lymphocytic Leukemia
Clin. Cancer Res.,
November 15, 2009;
15(22):
6947 - 6955.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Ravandi, A. Aribi, S. O'Brien, S. Faderl, D. Jones, A. Ferrajoli, X. Huang, S. York, S. Pierce, W. Wierda, et al.
Phase II Study of Alemtuzumab in Combination With Pentostatin in Patients With T-Cell Neoplasms
J. Clin. Oncol.,
November 10, 2009;
27(32):
5425 - 5430.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Bosch, P. Abrisqueta, N. Villamor, M. J. Terol, E. Gonzalez-Barca, C. Ferra, M. Gonzalez Diaz, E. Abella, J. Delgado, F. Carbonell, et al.
Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
September 20, 2009;
27(27):
4578 - 4584.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. S. Tam, T. D. Shanafelt, W. G. Wierda, L. V. Abruzzo, D. L. Van Dyke, S. O'Brien, A. Ferrajoli, S. A. Lerner, A. Lynn, N. E. Kay, et al.
De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience
Blood,
July 30, 2009;
114(5):
957 - 964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Gertner-Dardenne, C. Bonnafous, C. Bezombes, A.-H. Capietto, V. Scaglione, S. Ingoure, D. Cendron, E. Gross, J.-F. Lepage, A. Quillet-Mary, et al.
Bromohydrin pyrophosphate enhances antibody-dependent cell-mediated cytotoxicity induced by therapeutic antibodies
Blood,
May 14, 2009;
113(20):
4875 - 4884.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Foon, M. Boyiadzis, S. R. Land, S. Marks, A. Raptis, L. Pietragallo, D. Meisner, A. Laman, M. Sulecki, A. Butchko, et al.
Chemoimmunotherapy With Low-Dose Fludarabine and Cyclophosphamide and High Dose Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
February 1, 2009;
27(4):
498 - 503.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. T. Awan, N. E. Kay, M. E. Davis, W. Wu, S. M. Geyer, N. Leung, D. F. Jelinek, R. C. Tschumper, C. R. Secreto, T. S. Lin, et al.
Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab
Blood,
January 15, 2009;
113(3):
535 - 537.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. E. Kay, W. Wu, J. C. Byrd, B. Kabat, D. F. Jelinek, C. S. Zent, T. Call, T. Lin, and T. Shanafelt
Cyclophosphamide Remains An Important Component of Treatment in CLL Patients Receiving Pentostatin and Rituximab Based Chemoimmunotherapy
Blood (ASH Annual Meeting Abstracts),
November 16, 2008;
112(11):
43 - 43.
[Abstract]
|
 |
|

|
 |

|
 |
 
C. S. Tam, S. O'Brien, W. Wierda, H. Kantarjian, S. Wen, K.-A. Do, D. A. Thomas, J. Cortes, S. Lerner, and M. J. Keating
Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia
Blood,
August 15, 2008;
112(4):
975 - 980.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Nabhan
Frontline Therapy for Chronic Lymphocytic Leukemia: The Dilemma Continues
Clin. Cancer Res.,
July 1, 2008;
14(13):
4353 - 4353.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. W. Hauswirth and U. Jager
Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia
Haematologica,
January 1, 2008;
93(1):
14 - 19.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Bosch, A. Ferrer, N. Villamor, M. Gonzalez, J. Briones, E. Gonzalez-Barca, E. Abella, S. Gardella, L. Escoda, E. Perez-Ceballos, et al.
Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication
Clin. Cancer Res.,
January 1, 2008;
14(1):
155 - 161.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. G. Wierda
Treatments for Patients with Chronic Lymphocytic Leukemia
ASCO Educational Book,
January 1, 2008;
2008(1):
297 - 305.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al.
A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias
Blood,
September 15, 2007;
110(6):
1762 - 1769.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
PCR Immunochemotherapy for Previously Untreated CLL
Journal Watch Oncology and Hematology,
February 5, 2007;
2007(205):
1 - 1.
[Full Text]
|
 |
|

|
 |

|
 |
 
T. D. Shanafelt and N. E. Kay
Comprehensive Management of the CLL Patient: A Holistic Approach
Hematology,
January 1, 2007;
2007(1):
324 - 331.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|