High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: Long-term clinical and molecular follow-up

被引:143
作者
Apostolidis, J
Gupta, RK
Grenzelias, D
Johnson, PWM
Pappa, VI
Summers, KE
Salam, A
Adams, K
Norton, AJ
Amess, JAL
Matthews, J
Bradburn, M
Lister, TA
Rohatiner, AZS
机构
[1] St Bartholomews Hosp, Dept Med Oncol, Imperial Canc Res Fund, Med Oncol Unit, London EC1A 7BE, England
[2] St Bartholomews Hosp, Dept Histopathol & hematol, London EC1A 7BE, England
[3] Imperial Canc Res Fund, Ctr Stat Med, Inst Hlth Sci, Oxford, England
关键词
D O I
10.1200/JCO.2000.18.3.527
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. Patients and Methods: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow wets treated in vitro with anti-B-cell antibodies and complement. Results: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P = .04) and three or fewer treatment episodes before HDT (HR, 0.03; P = .001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up wets associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P < .001) and death (HR, 0.25; P = .02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. Conclusion: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting. J Clin Oncol 18:527-536. (C) 2000 by American Society of Clinical Oncology.
引用
收藏
页码:527 / 536
页数:10
相关论文
共 65 条
[1]   Patterns of outcome following recurrence after myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma [J].
Apostolidis, J ;
Foran, JM ;
Johnson, PWM ;
Norton, A ;
Amess, J ;
Matthews, J ;
Bradburn, M ;
Lister, TA ;
Rohatiner, AZS .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (01) :216-221
[2]   INTENSIVE THERAPY WITH PERIPHERAL-BLOOD PROGENITOR-CELL TRANSPLANTATION IN 60 PATIENTS WITH POOR-PROGNOSIS FOLLICULAR LYMPHOMA [J].
BASTION, Y ;
BRICE, P ;
HAIOUN, C ;
SONET, A ;
SALLES, G ;
MAROLLEAU, JP ;
ESPINOUSE, D ;
REYES, F ;
GISSELBRECHT, C ;
COIFFIER, B .
BLOOD, 1995, 86 (08) :3257-3262
[3]  
Bendandi M, 1998, BLOOD, V92, p153A
[4]   High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma [J].
Bierman, PJ ;
Vose, JM ;
Anderson, JR ;
Bishop, MR ;
Kessinger, A ;
Armitage, JO .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (02) :445-450
[5]  
Brittinger G, 1984, Hematol Oncol, V2, P269
[6]  
CARBONE PP, 1971, CANCER RES, V31, P1860
[7]   MULTIVARIATE SURVIVAL ANALYSIS USING COX REGRESSION-MODEL [J].
CHRISTENSEN, E .
HEPATOLOGY, 1987, 7 (06) :1346-1358
[8]  
COX DR, 1972, J R STAT SOC B, V34, P187
[9]   Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy [J].
Czuczman, MS ;
Grillo-López, AJ ;
White, CA ;
Saleh, M ;
Gordon, L ;
LoBuglio, AF ;
Jonas, C ;
Klippenstein, D ;
Dallaire, B ;
Varns, C .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (01) :268-276
[10]   INCIDENCE AND CHARACTERIZATION OF SECONDARY MYELODYSPLASTIC SYNDROME AND ACUTE MYELOGENOUS LEUKEMIA FOLLOWING HIGH-DOSE CHEMORADIOTHERAPY AND AUTOLOGOUS STEM-CELL TRANSPLANTATION FOR LYMPHOID MALIGNANCIES [J].
DARRINGTON, DL ;
VOSE, JM ;
ANDERSON, JR ;
BIERMAN, PJ ;
BISHOP, MR ;
CHAN, WC ;
MORRIS, ME ;
REED, EC ;
SANGER, WG ;
TARANTOLO, SR ;
WEISENBURGER, DD ;
KESSINGER, A ;
ARMITAGE, JO .
JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (12) :2527-2534