|
|
 Previous Article | Table of Contents | Next Article 
Response assessment in chronic lymphocytic leukemia after fludarabine plus
prednisone: clinical, pathologic, immunophenotypic, and molecular analysis
[see comments]
LE Robertson, YO Huh, JJ Butler, WC Pugh, C Hirsch-Ginsberg, S Stass, H Kantarjian and MJ Keating
Department of Hematology, University of Texas, M.D. Anderson Cancer Center,
Houston 77030.
The goals of this study were to evaluate the response to treatment in
chronic lymphocytic leukemia (CLL) according to clinical, pathologic,
immunophenotypic, and molecular features, as well as to address the
clinical significance of each finding. One hundred fifty-nine CLL patients
with either advanced Rai stage III or IV (81 patients) or progressive Rai
stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d
intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally
daily for 5 days). Thirty-six patients were previously untreated. The
response rates were 12% complete response (CR), 30% nodular complete
response (nCR), and 18% partial response (PR). In all patients who achieved
a complete response (both CR and nCR) less than 30% of nucleated cells were
lymphocytes on marrow aspirate differential analysis; however, nCR patients
had residual nodular and/or interstitial lymphocyte involvement on marrow
biopsy examination. There was no evidence of leukemic infiltration on
marrow biopsy examination in CR patients. With a median follow-up of 35
months, comparison of time to progression in the CR and nCR groups at 2
years showed a projected 87% versus 55% progression-free survival (P less
than .03). Residual disease assessment by flow cytometry using simultaneous
dual-color staining on blood and marrow lymphocytes was also performed on
each patient. Residual disease was determined by the expression of CD5 on B
lymphocytes and the monoclonality of surface light-chain expression. After
six courses of fludarabine plus prednisone, no residual disease was
detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of
the PRs. Clinical residual disease in PR patients with no residual disease
detectable by flow cytometry was limited to lymph-adenopathy. Time to
progression at 2 years was longer in CR and nCR patients having no residual
disease detected by flow cytometry (84% v 39% 2-year progression-free
survival, P less than .001). Posttreatment lg gene rearrangement analysis
using JH, J kappa, and C lambda probes demonstrated no rearranged bands and
a return to the germline configuration in five of seven CRs and two of
eight nCRs studied. The molecular studies were concordant with the dual-
parameter immunophenotype results and none of the patients who reverted to
a germline DNA pattern after treatment have experienced relapse. The
absence of detectable minimal residual disease by bone marrow biopsy,
dual-color flow cytometry, and lg gene rearrangement analysis is
achieveable in CLL with fludarabine and is predictive of the response
duration.
Volume 80,
Issue 1,
pp. 29-36,
07/01/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Motiwala, S. Majumder, H. Kutay, D. S. Smith, D. S. Neuberg, D. M. Lucas, J. C. Byrd, M. Grever, and S. T. Jacob
Methylation and Silencing of Protein Tyrosine Phosphatase Receptor Type O in Chronic Lymphocytic Leukemia
Clin. Cancer Res.,
June 1, 2007;
13(11):
3174 - 3181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Smit, D. Y.H. Hallaert, R. Spijker, B. de Goeij, A. Jaspers, A. P. Kater, M. H.J. van Oers, C. J.M. van Noesel, and E. Eldering
Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity
Blood,
February 15, 2007;
109(4):
1660 - 1668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Robak, J. Z. Blonski, J. Gora-Tybor, K. Jamroziak, J. Dwilewicz-Trojaczek, A. Tomaszewska, L. Konopka, B. Ceglarek, A. Dmoszynska, M. Kowal, et al.
Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2)
Blood,
July 15, 2006;
108(2):
473 - 479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Moreno, N. Villamor, D. Colomer, J. Esteve, E. Gine, A. Muntanola, E. Campo, F. Bosch, and E. Montserrat
Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia
Blood,
June 1, 2006;
107(11):
4563 - 4569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lamanna, M. Kalaycio, P. Maslak, J. G. Jurcic, M. Heaney, R. Brentjens, A. D. Zelenetz, D. Horgan, A. Gencarelli, K. S. Panageas, et al.
Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
April 1, 2006;
24(10):
1575 - 1581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Elter, P. Borchmann, H. Schulz, M. Reiser, S. Trelle, R. Schnell, M. Jensen, P. Staib, T. Schinkothe, H. Stutzer, et al.
Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial
J. Clin. Oncol.,
October 1, 2005;
23(28):
7024 - 7031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Keating, S. O'Brien, M. Albitar, S. Lerner, W. Plunkett, F. Giles, M. Andreeff, J. Cortes, S. Faderl, D. Thomas, et al.
Early Results of a Chemoimmunotherapy Regimen of Fludarabine, Cyclophosphamide, and Rituximab As Initial Therapy for Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
June 20, 2005;
23(18):
4079 - 4088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Tournilhac, B. Cazin, S. Lepretre, M. Divine, K. Maloum, A. Delmer, B. Grosbois, P. Feugier, F. Maloisel, F. Villard, et al.
Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia
Blood,
January 1, 2004;
103(1):
363 - 365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Weiss, P. G. Maslak, J. G. Jurcic, D. A. Scheinberg, T. B. Aliff, N. Lamanna, S. R. Frankel, S. E. Kossman, and D. Horgan
Pentostatin and Cyclophosphamide: An Effective New Regimen in Previously Treated Patients With Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
April 1, 2003;
21(7):
1278 - 1284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Keating, N. Chiorazzi, B. Messmer, R. N. Damle, S. L. Allen, K. R. Rai, M. Ferrarini, and T. J. Kipps
Biology and Treatment of Chronic Lymphocytic Leukemia
Hematology,
January 1, 2003;
2003(1):
153 - 175.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schulz, S. K. Klein, U. Rehwald, M. Reiser, A. Hinke, W.-U. Knauf, W.-E. Aulitzky, M. Hensel, M. Herold, D. Huhn, et al.
Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia
Blood,
October 16, 2002;
100(9):
3115 - 3120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Rawstron, B. Kennedy, P. A. S. Evans, F. E. Davies, S. J. Richards, A. P. Haynes, N. H. Russell, G. Hale, G. J. Morgan, A. S. Jack, et al.
Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy
Blood,
July 1, 2001;
98(1):
29 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Noy, R. Verma, M. Glenn, P. Maslak, Z. U. Rahman, J. R. Keenan, M. Weiss, D. Filippa, and A. D. Zelenetz
Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol
Blood,
April 1, 2001;
97(7):
1929 - 1936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. R. Rai, H. Dohner, M. J. Keating, and E. Montserrat
Chronic Lymphocytic Leukemia: Case-Based Session
Hematology,
January 1, 2001;
2001(1):
140 - 156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. R. Rai, B. L. Peterson, F. R. Appelbaum, J. Kolitz, L. Elias, L. Shepherd, J. Hines, G. A. Threatte, R. A. Larson, B. D. Cheson, et al.
Fludarabine Compared with Chlorambucil as Primary Therapy for Chronic Lymphocytic Leukemia
N. Engl. J. Med.,
December 14, 2000;
343(24):
1750 - 1757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Robak, J. Z. Blonski, M. Kasznicki, M. Blasinska-Morawiec, E. Krykowski, A. Dmoszynska, H. Mrugala-Spiewak, A. B. Skotnicki, W. Nowak, L. Konopka, et al.
Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial
Blood,
October 15, 2000;
96(8):
2723 - 2729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Mauro, R. Foa, D. Giannarelli, I. Cordone, S. Crescenzi, E. Pescarmona, R. Sala, R. Cerretti, and F. Mandelli
Clinical Characteristics and Outcome of Young Chronic Lymphocytic Leukemia Patients: A Single Institution Study of 204 Cases
Blood,
July 15, 1999;
94(2):
448 - 454.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.J. Keating, S. O'Brien, S. Lerner, C. Koller, M. Beran, L.E. Robertson, E. J Freireich, E. Estey, and H. Kantarjian
Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy
Blood,
August 15, 1998;
92(4):
1165 - 1171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Jennings and K. A. Foon
Recent Advances in Flow Cytometry: Application to the Diagnosis of Hematologic Malignancy
Blood,
October 15, 1997;
90(8):
2863 - 2892.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Kolesar, A. K. Morris, and J. G. Kuhn
Review : Purine nucleoside analogues: Fludarabine, pentostatin, and cladribine: Part 1: Fludarabine
Journal of Oncology Pharmacy Practice,
January 1, 1996;
2(3):
160 - 181.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Rozman and E. Montserrat
Chronic Lymphocytic Leukemia
N. Engl. J. Med.,
October 19, 1995;
333(16):
1052 - 1057.
[Full Text]
[PDF]
|
|
|
|
|
