Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Oct;68(4):767–774. doi: 10.1038/bjc.1993.425

Combination chemotherapy for intermediate and high grade non-Hodgkin's lymphoma.

H S Dhaliwal 1, A Z Rohatiner 1, W Gregory 1, M A Richards 1, P W Johnson 1, J S Whelan 1, C J Gallagher 1, J Matthews 1, T S Ganesan 1, M J Barnett 1, et al.
PMCID: PMC1968617  PMID: 8398705

Abstract

One hundred and eighteen consecutive adults with newly diagnosed intermediate and high-grade non-Hodgkin's lymphoma were treated with chemotherapy comprising Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone with mid-cycle Methotrexate (MTX) and leucovorin rescue ('CHOP-M'). Intrathecal MTX was given with each treatment cycle as central nervous system (CNS) prophylaxis. 'Clinical remission' was achieved in 70/110 evaluable patients (64%), complete remission: 45/110, (41%), good partial remission: 25/110 (23%). Twenty two patients (19%) died prior to completion of therapy, 18 patients had persistent disease. Hyponatremia (< 137 mmol l-1), advanced age and hypoalbuminaemia (< 32 g l-1) correlated adversely with achievement of CR (P = 0.0007, 0.0005 and 0.04 respectively). With a minimum follow up of 41 years, 47 of the seventy patients (67%) in whom clinical remission was achieved remain well, 19 have developed recurrent disease, resulting in an actuarial projected remission duration of 70% at 8 years. Four died in CR. There has been only one isolated CNS recurrence. On univariate analysis, hypoalbuminaemia, hyponatremia and beta 2 microglobulin (> 3) correlated with unfavourable outcome in terms of duration of remission (P = 0.0009, 0.007 and 0.04 respectively). On multivariate analysis, only the serum sodium (0.002) and advanced age (0.01) were predictive for remission duration. Fifty patients (45%) are alive, the overall actuarial projected survival is thus 42% at 8 years. On univariate analysis, age, hypoalbuminaemia, hyponatraemia, liver involvement and the presence of B symptoms correlated unfavourably with survival. On multivariate analysis, hypoalbuminaemia, advanced age, hyponatraemia, male gender (aged > 50) and diffuse large cell or large cell, immunoblastic histology (Working Formulation) had an adverse effect (P = 0.003, < 0.0001, < 0.0001, 0.002, and 0.03). It was further possible, using cut-off points of 32 g l-1 and 136 mmol l-1 for albumin and sodium respectively to define prognostic categories for patients who differed significantly in terms of survival.

Full text

PDF
767

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armitage J. O., Dick F. R., Corder M. P., Garneau S. C., Platz C. E., Slymen D. J. Predicting therapeutic outcome in patients with diffuse histiocytic lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1982 Nov 1;50(9):1695–1702. doi: 10.1002/1097-0142(19821101)50:9<1695::aid-cncr2820500907>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  2. Berd D., Cornog J., DeConti R. C., Levitt M., Bertino J. R. Long-term remission in diffuse histiocytic lymphoma treated with combination sequential chemotherapy. Cancer. 1975 Apr;35(4):1050–1054. doi: 10.1002/1097-0142(197504)35:4<1050::aid-cncr2820350406>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  3. Boyd D. B., Coleman M., Papish S. W., Topilow A., Kopel S. K., Bernhardt B., Files J. C., Schwartz S., Gaynor M., McDermott D. COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma. J Clin Oncol. 1988 Mar;6(3):425–433. doi: 10.1200/JCO.1988.6.3.425. [DOI] [PubMed] [Google Scholar]
  4. Cabanillas F., Burgess M. A., Bodey G. P., Freireich E. J. Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type. Am J Med. 1983 Mar;74(3):382–388. doi: 10.1016/0002-9343(83)90955-5. [DOI] [PubMed] [Google Scholar]
  5. Coiffier B., Bryon P. A., Ffrench M., Blanc M., Sebban C., Berger F., Viala J. J. Intensive chemotherapy in aggressive lymphomas: updated results of LNH-80 protocol and prognostic factors affecting response and survival. Blood. 1987 Nov;70(5):1394–1399. [PubMed] [Google Scholar]
  6. Coiffier B., Gisselbrecht C., Vose J. M., Tilly H., Herbrecht R., Bosly A., Armitage J. O. Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs. J Clin Oncol. 1991 Feb;9(2):211–219. doi: 10.1200/JCO.1991.9.2.211. [DOI] [PubMed] [Google Scholar]
  7. Coleman M., Gerstein G., Topilow A., Lebowicz J., Berhardt B., Chiarieri D., Silver R. T., Pasmantier M. W. Advances in chemotherapy for large cell lymphoma. Semin Hematol. 1987 Apr;24(2 Suppl 1):8–20. [PubMed] [Google Scholar]
  8. Cowan R. A., Jones M., Harris M., Steward W. P., Radford J. A., Wagstaff J., Deakin D. P., Crowther D. Prognostic factors in high and intermediate grade non-Hodgkin's lymphoma. Br J Cancer. 1989 Feb;59(2):276–282. doi: 10.1038/bjc.1989.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Danieu L., Wong G., Koziner B., Clarkson B. Predictive model for prognosis in advanced diffuse histiocytic lymphoma. Cancer Res. 1986 Oct;46(10):5372–5379. [PubMed] [Google Scholar]
  10. De Vita V. T., Jr, Hubbard S. M., Longo D. L. The chemotherapy of lymphomas: looking back, moving forward--the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1987 Nov 15;47(22):5810–5824. [PubMed] [Google Scholar]
  11. DeVita V. T., Jr, Canellos G. P., Chabner B., Schein P., Hubbard S. P., Young R. C. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248–250. doi: 10.1016/s0140-6736(75)91142-3. [DOI] [PubMed] [Google Scholar]
  12. Dixon D. O., Neilan B., Jones S. E., Lipschitz D. A., Miller T. P., Grozea P. N., Wilson H. E. Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience. J Clin Oncol. 1986 Mar;4(3):295–305. doi: 10.1200/JCO.1986.4.3.295. [DOI] [PubMed] [Google Scholar]
  13. Fisher R. I., DeVita V. T., Jr, Hubbard S. M., Longo D. L., Wesley R., Chabner B. A., Young R. C. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. Ann Intern Med. 1983 Mar;98(3):304–309. doi: 10.7326/0003-4819-98-3-304. [DOI] [PubMed] [Google Scholar]
  14. Fisher R. I., Gaynor E. R., Dahlberg S., Oken M. M., Grogan T. M., Mize E. M., Glick J. H., Coltman C. A., Jr, Miller T. P. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002–1006. doi: 10.1056/NEJM199304083281404. [DOI] [PubMed] [Google Scholar]
  15. Fisher R. I., Miller T. P., Dana B. W., Jones S. E., Dahlberg S., Coltman C. A., Jr Southwest oncology group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas. Semin Hematol. 1987 Apr;24(2 Suppl 1):21–25. [PubMed] [Google Scholar]
  16. Gallagher C. J., Copplestone A., Meikle J. D., Lister T. A. The treatment of disseminated non-Hodgkin's lymphoma of unfavourable histology. Cancer Chemother Pharmacol. 1982;8(2):237–241. doi: 10.1007/BF00255490. [DOI] [PubMed] [Google Scholar]
  17. Gobbi P. G., Gendarini A., Crema A., Cavalli C., Attardo-Parrinello G., Federico M., Di Prisco U., Ascari E. Serum albumin in Hodgkin's disease. Cancer. 1985 Jan 15;55(2):389–393. doi: 10.1002/1097-0142(19850115)55:2<389::aid-cncr2820550216>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  18. Guglielmi C., Amadori S., Martelli M., Dragoni F., Mandelli F. The F-MACHOP sequential combination chemotherapy regimen in advanced diffuse aggressive lymphomas: long-term results. Ann Oncol. 1991 May;2(5):365–371. doi: 10.1093/oxfordjournals.annonc.a057958. [DOI] [PubMed] [Google Scholar]
  19. Hoskins P. J., Ng V., Spinelli J. J., Klimo P., Connors J. M. Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B. J Clin Oncol. 1991 Feb;9(2):220–226. doi: 10.1200/JCO.1991.9.2.220. [DOI] [PubMed] [Google Scholar]
  20. Jagannath S., Velasquez W. S., Tucker S. L., Fuller L. M., McLaughlin P. W., Manning J. T., North L. B., Cabanillas F. C. Tumor burden assessment and its implication for a prognostic model in advanced diffuse large-cell lymphoma. J Clin Oncol. 1986 Jun;4(6):859–865. doi: 10.1200/JCO.1986.4.6.859. [DOI] [PubMed] [Google Scholar]
  21. Klimo P., Connors J. M. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596–602. doi: 10.7326/0003-4819-102-5-596. [DOI] [PubMed] [Google Scholar]
  22. Kwak L. W., Halpern J., Olshen R. A., Horning S. J. Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis. J Clin Oncol. 1990 Jun;8(6):963–977. doi: 10.1200/JCO.1990.8.6.963. [DOI] [PubMed] [Google Scholar]
  23. Miller T. P., Dahlberg S., Weick J. K., Files J. C., Eyre H. J., Pendergrass K. B., Fisher R. I. Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study. J Clin Oncol. 1990 Dec;8(12):1951–1958. doi: 10.1200/JCO.1990.8.12.1951. [DOI] [PubMed] [Google Scholar]
  24. Osterlind K., Andersen P. K. Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation. Cancer Res. 1986 Aug;46(8):4189–4194. [PubMed] [Google Scholar]
  25. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. doi: 10.1038/bjc.1977.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schein P. S., DeVita V. T., Jr, Hubbard S., Chabner B. A., Canellos G. P., Berard C., Young R. C. Bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP) combination chemotherapy in the treatment of advanced diffuse histiocytic lymphoma. Ann Intern Med. 1976 Oct;85(4):417–422. doi: 10.7326/0003-4819-85-4-417. [DOI] [PubMed] [Google Scholar]
  27. Shipp M. A., Harrington D. P., Klatt M. M., Jochelson M. S., Pinkus G. S., Marshall J. L., Rosenthal D. S., Skarin A. T., Canellos G. P. Identification of major prognostic subgroups of patients with large-cell lymphoma treated with m-BACOD or M-BACOD. Ann Intern Med. 1986 Jun;104(6):757–765. doi: 10.7326/0003-4819-104-6-757. [DOI] [PubMed] [Google Scholar]
  28. Shipp M. A., Yeap B. Y., Harrington D. P., Klatt M. M., Pinkus G. S., Jochelson M. S., Rosenthal D. S., Skarin A. T., Canellos G. P. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84–93. doi: 10.1200/JCO.1990.8.1.84. [DOI] [PubMed] [Google Scholar]
  29. Skarin A. T., Canellos G. P., Rosenthal D. S., Case D. C., Jr, MacIntyre J. M., Pinkus G. S., Moloney W. C., Frei E., 3rd Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol. 1983 Feb;1(2):91–98. doi: 10.1200/JCO.1983.1.2.91. [DOI] [PubMed] [Google Scholar]
  30. Steward W. P., Todd I. D., Harris M., Jones J. M., Blackledge G., Wagstaff J., Anderson H., Wilkinson P. M., Crowther D. A multivariate analysis of factors affecting survival in patients with high-grade histology non-Hodgkin's lymphoma. Eur J Cancer Clin Oncol. 1984 Jul;20(7):881–889. doi: 10.1016/0277-5379(84)90159-7. [DOI] [PubMed] [Google Scholar]
  31. Stuart N. S., Blackledge G. R., Child J. A., Fletcher J., Perren T. J., O'Brien C. J., Jones E. L., Ellis I. O., Kavanagh J. A., Kelly K. A. A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma--intensive two-phase chemotherapy. Cancer Chemother Pharmacol. 1988;22(2):141–146. doi: 10.1007/BF00257312. [DOI] [PubMed] [Google Scholar]
  32. Velasquez W. S., Jagannath S., Tucker S. L., Fuller L. M., North L. B., Redman J. R., Swan F., Hagemeister F. B., McLaughlin P., Cabanillas F. Risk classification as the basis for clinical staging of diffuse large-cell lymphoma derived from 10-year survival data. Blood. 1989 Aug 1;74(2):551–557. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES