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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Aug;85(3):325–332. doi: 10.1054/bjoc.2000.1928

Glomerular filtration rate prior to high-dose melphalan 200 mg/m2 as a surrogate marker of outcome in patients with myeloma

B Sirohi 1, R Powles 1, S Kulkarni 1, C Rudin 1, R Saso 1, A Rigg 1, C Horton 1, S Singhal 1, J Mehta 1, J Treleaven 1
PMCID: PMC2364060  PMID: 11487259

Abstract

We correlated age and body surface area corrected glomerular filtration rate (GFR) at the time of high-dose melphalan (HDM) administration with treatment-related toxicity (TT), time to disease progression and survival. Between 8/85 and 6/98, 144 newly diagnosed myeloma patients with a median age of 53 years (range, 31–72) received infusional chemotherapy with vincristine, doxorubicin and methylprednisolone, with/without cyclophosphamide or verapamil, followed by HDM 200 mg/m2and stem cell rescue. An additional patient received HDM at diagnosis. GFR was below normal in 38 patients (26%). At presentation, patients with low GFR at the time of HDM had higher serum creatinine, β2M, stage III disease, calcium and Bence–Jones proteinuria. Toxic deaths post-HDM were similar in both groups (2/38 (5%) vs. 4/107 (4%)), though patients with low GFR had more oral mucositis (P< 0.0001), diarrhoea (P = 0.005) and infections (P = 0.04). The response and relapse rates of the 2 groups were not substantially different, but the median overall survival (OS) was significantly shorter in patients with low GFR (5.1 vs 7.5 years, P = 0.015). Multivariate analysis showed that a normal GFR and being in CR at the time of HDM were predictive of longer OS. We conclude that in context of high-dose chemotherapy for myeloma, dose of melphalan should not be modified in patients with low GFR and that early intensive treatment at relapse may improve results in patients with abnormal renal function. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: myeloma, glomerular filtration rate, morbidity, outcome

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Selected References

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  1. Attal M., Harousseau J. L., Stoppa A. M., Sotto J. J., Fuzibet J. G., Rossi J. F., Casassus P., Maisonneuve H., Facon T., Ifrah N. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996 Jul 11;335(2):91–97. doi: 10.1056/NEJM199607113350204. [DOI] [PubMed] [Google Scholar]
  2. Barlogie B., Jagannath S., Desikan K. R., Mattox S., Vesole D., Siegel D., Tricot G., Munshi N., Fassas A., Singhal S. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999 Jan 1;93(1):55–65. [PubMed] [Google Scholar]
  3. Björkstrand B., Goldstone A. H., Ljungman P., Brandt L., Brunet S., Carlson K., Prentice G., Cavo M., Samson D., de Laurenzi A. Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation. Leuk Lymphoma. 1994 Oct;15(3-4):265–272. doi: 10.3109/10428199409049723. [DOI] [PubMed] [Google Scholar]
  4. Britton K. E., Nimmon C. C., Whitfield H. N., Hendry W. F., Wickham J. E. Obstructive nephropathy: successful evaluation with radionuclides. Lancet. 1979 Apr 28;1(8122):905–907. doi: 10.1016/s0140-6736(79)91377-1. [DOI] [PubMed] [Google Scholar]
  5. Cunningham D., Paz-Ares L., Milan S., Powles R., Nicolson M., Hickish T., Selby P., Treleavan J., Viner C., Malpas J. High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol. 1994 Apr;12(4):759–763. doi: 10.1200/JCO.1994.12.4.759. [DOI] [PubMed] [Google Scholar]
  6. Cunningham D., Powles R., Malpas J., Raje N., Milan S., Viner C., Montes A., Hickish T., Nicolson M., Johnson P. A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol. 1998 Jul;102(2):495–502. doi: 10.1046/j.1365-2141.1998.00795.x. [DOI] [PubMed] [Google Scholar]
  7. Durie B. G., Salmon S. E. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842–854. doi: 10.1002/1097-0142(197509)36:3<842::aid-cncr2820360303>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  8. Forgeson G. V., Selby P., Lakhani S., Zulian G., Viner C., Maitland J., McElwain T. J. Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients. Br J Cancer. 1988 Oct;58(4):469–473. doi: 10.1038/bjc.1988.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gore M. E., Selby P. J., Viner C., Clark P. I., Meldrum M., Millar B., Bell J., Maitland J. A., Milan S., Judson I. R. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet. 1989 Oct 14;2(8668):879–882. doi: 10.1016/s0140-6736(89)91548-1. [DOI] [PubMed] [Google Scholar]
  10. Kergueris M. F., Milpied N., Moreau P., Harousseau J. L., Larousse C. Pharmacokinetics of high-dose melphalan in adults: influence of renal function. Anticancer Res. 1994 Nov-Dec;14(6A):2379–2382. [PubMed] [Google Scholar]
  11. Mansi J., da Costa F., Viner C., Judson I., Gore M., Cunningham D. High-dose busulfan in patients with myeloma. J Clin Oncol. 1992 Oct;10(10):1569–1573. doi: 10.1200/JCO.1992.10.10.1569. [DOI] [PubMed] [Google Scholar]
  12. Merlini G., Waldenström J. G., Jayakar S. D. A new improved clinical staging system for multiple myeloma based on analysis of 123 treated patients. Blood. 1980 Jun;55(6):1011–1019. [PubMed] [Google Scholar]
  13. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  14. Moreau P., Milpied N., Mahé B., Juge-Morineau N., Rapp M. J., Bataille R., Harousseau J. L. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant. 1999 May;23(10):1003–1006. doi: 10.1038/sj.bmt.1701763. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Powles R., Raje N., Milan S., Millar B., Shepherd V., Mehta J., Singhal S., Kulkarni S., Viner C., Gore M. Outcome assessment of a population-based group of 195 unselected myeloma patients under 70 years of age offered intensive treatment. Bone Marrow Transplant. 1997 Sep;20(6):435–443. doi: 10.1038/sj.bmt.1700917. [DOI] [PubMed] [Google Scholar]
  17. Raje N., Powles R., Horton C., Millar B., Shepherd V., Middleton G., Kulkarni S., Eisen T., Mehta J., Singhal S. Comparison of marrow vs blood-derived stem cells for autografting in previously untreated multiple myeloma. Br J Cancer. 1997;75(11):1684–1689. doi: 10.1038/bjc.1997.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Raje N., Powles R., Kulkarni S., Milan S., Middleton G., Singhal S., Mehta J., Millar B., Viner C., Raymond J. A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma. Br J Haematol. 1997 Apr;97(1):153–160. doi: 10.1046/j.1365-2141.1997.d01-2122.x. [DOI] [PubMed] [Google Scholar]
  19. Selby P., Zulian G., Forgeson G., Nandi A., Milan S., Meldrum M., Viner C., Osborne R., Malpas J. S., McElwain T. J. The development of high dose melphalan and of autologous bone marrow transplantation in the treatment of multiple myeloma: Royal Marsden and St Bartholomew's Hospital studies. Hematol Oncol. 1988 Apr-Jun;6(2):173–179. doi: 10.1002/hon.2900060218. [DOI] [PubMed] [Google Scholar]
  20. Siegel D. S., Desikan K. R., Mehta J., Singhal S., Fassas A., Munshi N., Anaissie E., Naucke S., Ayers D., Spoon D. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood. 1999 Jan 1;93(1):51–54. [PubMed] [Google Scholar]
  21. Sirohi B., Powles R., Mehta J., Raje N., Kulkarni S., Ramiah V., Saso R., Horton C., Bhagwati N., Singhal S. Complete remission rate and outcome after intensive treatment of 177 patients under 75 years of age with IgG myeloma defining a circumscribed disease entity with a new staging system. Br J Haematol. 1999 Dec;107(3):656–666. doi: 10.1046/j.1365-2141.1999.01744.x. [DOI] [PubMed] [Google Scholar]
  22. Sirohi B., Powles R., Treleaven J., Mainwaring P., Kulkarni S., Pandha H., Bhagwati N., Horton C., Singhal S., Mehta J. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant. 2000 Mar;25(5):533–539. doi: 10.1038/sj.bmt.1702188. [DOI] [PubMed] [Google Scholar]
  23. Toto R. D., Kirk K. A., Coresh J., Jones C., Appel L., Wright J., Campese V., Olutade B., Agodoa L. Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. J Am Soc Nephrol. 1997 Feb;8(2):279–287. doi: 10.1681/ASN.V82279. [DOI] [PubMed] [Google Scholar]
  24. Tricot G., Alberts D. S., Johnson C., Roe D. J., Dorr R. T., Bracy D., Vesole D. H., Jagannath S., Meyers R., Barlogie B. Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study. Clin Cancer Res. 1996 Jun;2(6):947–952. [PubMed] [Google Scholar]
  25. Vesole D. H., Tricot G., Jagannath S., Desikan K. R., Siegel D., Bracy D., Miller L., Cheson B., Crowley J., Barlogie B. Autotransplants in multiple myeloma: what have we learned? Blood. 1996 Aug 1;88(3):838–847. [PubMed] [Google Scholar]

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