#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Achieving Bcl-2/IgH negativity in peripheral blood/bone marrow after therapy implies better prognosis for patients with follicular lymphoma


Authors: D. Belada 1;  L. Smolej 1;  P. Štěpánková 1;  M. Beránek 2;  D. Dvořáková 3;  J. Bukač 4;  J. Malý 1
Authors‘ workplace: Oddělení klinické hematologie II. interní kliniky Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Jaroslav Malý, CSc. 1;  Ústav klinické biochemie a diagnostiky Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Vladimír Palička, CSc. 2;  Centrum molekulární biologie a genové terapie Interní hematoonkologické kliniky Lékařské fakulty MU a FN Brno, pracoviště Bohunice přednosta prof. MUDr. Jiří Vorlíček, CSc. 3;  Ústav lékařské biofyziky Lékařské fakulty UK Hradec Králové, přednosta doc. Ing. Josef Hanuš, CSc. 4
Published in: Vnitř Lék 2007; 53(10): 1057-1063
Category: Original Contributions

Overview

Bcl-2/IgH rearrangement is a characteristic molecular rearrangement in patients with follicular lymphoma (FL), yet its prognostic significance is still unclear.

Objective:
Evaluation of the implications of achieving Bcl-2/IgH negativity for the prognosis of FL patients. Twenty seven patients (54 %) were receiving only chemotherapy (CHT), 23 patients (46 %) were receiving chemotherapy combined with monoclonal antibody anti/CD20, rituximab (R-CHT).

Results:
Molecular genetic remission was achieved in 7 out of 11 patients (64 %) after R-CHT, and only in 2 out of 14 patients (14 %) after CHT – this difference was statistically significant (p = 0.037). 4 weekly doses of rituximab were administered in a sequence to 17 out of 27 patients who had received only chemotherapy and failed to achieve complete remission. 12 out of 17 patients (71 %) on this therapy were Bcl-2/IgH positive prior to treatment. 7 out of 12 (58 %) patients were no longer Bcl-2/IgH positive in a check performed after one month; the remaining 2 out of 5 patients had a negative Bcl-2/IgH record for the interval of 3 months (1 patient) or 6 (1 patient) months, respectively. The following factors were associated with the achievement of Bcl-2/IgH negativity at any point during the treatment: age < 65 years (p = 0.02) and performance status 0 + 1 according to WHO at baseline (p = 0.02). Patients who were Bcl-2/IgH negative after treatment had a lower recurrence/progression risk rate than the Bcl-2/IgH positive group of patients, i.e. 27 % vs. 75 % (p = 0.03), and a higher chance for progression-free survival, i.e. 81 % vs. 38 % (p = 0.004), event-free survival, i.e. 74 % vs. 38 % (p = 0.01), and overall survival, i.e. 87 % vs. 74 % (p = 0.05) at 2 years.

Conclusion:
In our experience, achieving Bcl-2/IgH negativity after follicular lymphoma therapy implies a better prognosis.

Keywords:
Bcl-2/IgH – follicular lymphoma 2 minimum residual disease – rituximab – prognosis


Sources

1. Apostolidis J, Gupta RK, Granzelias D et al. High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up. J Clin Oncol 2000; 18: 527-536.

2. Armitage J, Wiesenburger D New approach to classifying non-Hodgkin´s lymphomas. Clinical features of the major histologic subtypes. J Clin Oncol 1998; 16: 2780-2795.

3. Bakhshi A, Wright JJ, Graniger W et al. Mechanism of the t(14;18) chromosomal translocation: structural analysis of the both derivate 14 and 18 reciprocal partners. Proc Natl Acad Sci USA 1987; 84: 2396-2400.

4. Colombat P, Salles G, Brousse N et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood 2001; 97: 101-106.

5. Czuczman MS, Grillo-López AJ, McLauglin P, White CA et at. Clearing of celles bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy. Ann Oncol 2001; 12: 109-114.

6. Foran JM, Gupta RK, Cunningmam D et al. A UK multicentre phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response. Br J Heamatol 2000; 109: 81-88.

7. Glass AG, Karnell LH, Menck HR. The national Cancer Data Base report on non-Hodgkin’s lymphoma. Cancer 1997; 80: 2311-2320.

8. Gribben JG, Freedman AS et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Eng J Med 1991; 325: 1525-1531.

9. Gribben JG, Neuberg D, Barber M et al. Detection of Residual Lymphoma Cells by Polymerase Chain Reaction in Peripheral Blood Is Significantly Less Predictive for Relapse Than Detection in Bone Marrow. Blood 1994; 83: 3800-3807.

10. Cheson BD, Horning SJ, Coiffier B et al. Report of an international workshop to standardize response criteria for non‑Hodgkin’s lymphomas. J Clin Oncol 1999; 17: 1244. Erratum in: J Clin Oncol 2000; 18: 2351.

11. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481.

12. Ladetto M, Corradini P, Vallet S et al. High rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: a multicenter, prospective study by the Gruppo Italiano Trapianto Middolo Osseo (GIMTO). Blood 2002; 100: 1559-1564.

13. Lopez-Guillermo A, Cabanillas F, McLauglin P et al. Molecular response assessed by PCR is the most important factor predicting failure-gree survival in indolent follicular lymphoma: Update of the MDACC series. Ann Oncol 2000; 11(Suppl 1): S137-S140.

14. Mahé B, Milpied N, Mellerin MP et al. PCR detection of residual Bcl-2/IgH-positive cells after high-dose therapy with autologous stem cell transplantation is a prognostic factor for event-free survival in patients with low-grade follicular non-Hodgkin’s lymphoma. Bone Marrow Transpl 2003; 31: 467-473.

15. Mandigers CM, Meijerink PP, Mensink EM et al. Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma. Blood 2001; 98: 940-944.

16. Papajík T, Jedličková K, Krigerová E et al. Polymerase chain reaction detection of cells carrying t(14;18) in bone marrow of patients with follicular and diffuse large B-cell lymphoma: the importance of analysis at diagnosis and significance of long term follow-up. Neoplasma 2001; 6: 501-505.

17. Pezzela F, Jones M, Ersboll J et al. Evaluation of bcl-2 protein expression and 14;18 translocation as prognostic markers in follicular lymphoma. British J Can 1992; 65: 87-89.

18. Rambaldi A, Lazzari M, Manzoni C et al. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood 2002; 99: 856-862.

19. Reff ME, Carner K et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994; 83: 435-445.

20. Rogers J, Jackson J, Rosenberg J et al. Clearance of bcl-2 t(14;18) from peripheral blood and bone marrow in patients with relapsed low-grade or follicular lymphoma following single-agent therapy with the chimaeric anti-CD20 antibody IDEC-C2B8. Ann Oncol 1996; 7: 108a (abstract).

21. Summers KE, Davies AJ, Matthews J et al. The relative role of peripheral blood and bone marrow for monitoring molecular evidence of disease in follicular lymphoma by quantitative real-time polymerace Chin reaction. Br J Haematol 2002; 118: 563-566.

22. Tsijumoto Y, Finger L, Yunis J et al. Cloning of the chromosome braekpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984; 226: 1097-1099.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 10

2007 Issue 10

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#