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Stem Cell Transplantation in Myeloma

Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure

Abstract

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5–7 g/m2 + G-CSF, 5 μg/kg/day (patients 1–3, 5 and 6) or G-CSF, 15 μg/kg/day alone (patient No. 4). Four patients (Nos 1–4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1–3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/μl and 20000 platelets/μl were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3–4 infectious complications. Transplant-related toxicity included grade 3–4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.

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References

  1. Alexanian R, Barlogie B, Dixon D . Renal failure in multiple myeloma: pathogenesis and prognostic implications Arch Intern Med 1990 150: 1693–1695

    Article  CAS  Google Scholar 

  2. Cavo M, Baccarani M, Galieni P, Gobbi M, Tura S . Renal failure in multiple myeloma. A study of the presenting findings, response to treatment and prognosis in 26 patients Nouv Rev Fr Hematol 1986 28: 147–152

    CAS  PubMed  Google Scholar 

  3. Knudsen L, Hippe E, Hjorth M, Holmberg E, Westin J . Renal function in newly diagnosed multiple myeloma – a demographic study of 1353 patients Eur J Haematol 1994 53: 207–212

    Article  CAS  Google Scholar 

  4. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R . A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma New Engl J Med 1996 335: 91–97

    Article  CAS  Google Scholar 

  5. Barlogie B, Jagannath S, Vesole DH Nancke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G . Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma Blood 1997 98: 789–793

    Google Scholar 

  6. Alberts DS, Chen HG, Benz D, Mason NL . Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan Br J Cancer 1981 43: 330–334

    Article  CAS  Google Scholar 

  7. Osterborg A, Ehrsson H, Eksberg S Wallin I, Mellstedt H . Pharmacokinetics of oral melphalan in relation to renal function in multiple myeloma patients Eur J Cancer Clin Oncol 1989 25: 899–903

    Article  CAS  Google Scholar 

  8. Cornwell IGG, Pajak TF, McIntyre OR Kochwa S, Dosik H . Influence of renal failure on myelosuppressive effets of melphalan: Cancer and Leukemia Group B experience Cancer Treat Rep 1982 66: 475–481

    PubMed  Google Scholar 

  9. Pecherstrofer M, Zimmer-Roth I, Weidinger S, Irsigler K, Halbmayer WM, Ulrich W, Fischer M, Baumgartner G . High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure Clin Invest 1994 72: 522–525

    Google Scholar 

  10. Rebibou JM, Caillot D, Casanovas RO Tanter Y, Maillard N, Solary E, Rifle G, Guy H . Peripheral blood stem cell transplantation in a multiple myeloma patient with end-stage renal failure Bone Marrow Transplant 1997 20: 63–65

    Article  CAS  Google Scholar 

  11. Ballester OF, Tummala R, Janssen WE, Fields KK, Hiemenz JW, Goldstein SC, Perkins JB, Sullivan DM, Rosen R, Sackstein R, Zorsky P, Saez R, Elfenblein GJ . High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency Bone Marrow Transplant 1997 20: 653–656

    Article  CAS  Google Scholar 

  12. Tricot G, Alberts DS, Johnson C, Roe DJ, Dorr RT, Bracy D, Vesole DH, Jagannath S, Meyers R, Barlogie B . Safety of autotransplant with high-dose melphalan in renal failure: a pharmacokinetics and toxicity study Clin Cancer Res 1996 2: 947–952

    CAS  PubMed  Google Scholar 

  13. Reiter E, Kalhs P, Keil F, Rabitsch W, Gissingler H, Mayer G, Worel N, Lechner K, Greinix HT . Effects of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature Ann Hematol 1999 78: 189–191

    Article  CAS  Google Scholar 

  14. Chronic Leukemia-Myeloma Task Force . Proposed guidelines for protocol studies: II. Plasma cell myeloma Cancer Chemother Rep 1973 3: 145–157

    Google Scholar 

  15. Alexanian R, Barlogie B, Tucker S . VAD-based regimens as primary treatment for multiple myeloma Am J Hematol 1990 33: 86–89

    Article  CAS  Google Scholar 

  16. Bladé J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D . Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation Br J Haematol 1998 102: 1115–1123

    Article  Google Scholar 

  17. Kulkarni S, Rodriguez M, Lafuente A, Mateos P, Metha J, Singhal S, Saso R, Tait D, Treleaven JG, Powles RL . Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD) Bone Marrow Transplant 1999 23: 803–807

    Article  CAS  Google Scholar 

  18. Siegel DS, Desikan KR, Metha J, Singhal S, Fassas A, Munshi N, Anaissie E, Nancke S, Ayers D, Spoon D, Vesole D, Tricot G, Barlogie B . Age is not a prognostic variable with autotransplants for multiple myeloma Blood 1999 93: 51–54

    CAS  PubMed  Google Scholar 

  19. Bagley CM, Bostick FW, DeVita VT . Clinical pharmacology of cyclophosphamide Cancer Res 1978 88: 226–233

    Google Scholar 

  20. Alegre A, Diaz Mediavilla J, san Miguel J, Martínez R, García Laraña J, Sureda A, Lahuerta JJ, Morales D, Bladé J, Caballero D, De la Rubia J, Escudero A, Díez Martín JL, Hernández Navarro F, Rifón J, Odriozola J, Brunet S, De la Serna J, Besalduch J, Vidal MJ, Solano C, Leon A, Sánchez JJ, Martínez Chamorro C, Fernández Rañada JM . Autologous peripheral blood stem cell transplantation for multiple myeloma: a report of 259 cases from the Spanish Registry Bone Marrow Transplant 1998 21: 133–140

    Article  CAS  Google Scholar 

  21. Cavo M, Bandini G, Benni M, Gozzetti A, Ronconi S, Rosti GA, Zamagni E, Lemoli RM, Bonini A, Belardinelli A, Motta MR, Rizzi S, Tura S . High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma Bone Marrow Transplant 1998 22: 27–32

    Article  CAS  Google Scholar 

  22. Hassan M, Oberg G, Ehrsson H, Ehrnebo M, Wallin I, Smedyr B, Totterman T, Eksborg S, Simonsson B . Pharmacokinetic and metabolic studies of high-dose busulfan in adults Eur J Clin Pharmacol 1989 36: 525–530

    Article  CAS  Google Scholar 

  23. Cornwell GG, Pajak TF, McIntyre ER, Kochwa S, Dosik H . Influence of renal failure on the myelosuppressive effects of melphalan: cancer and leukemia group B experience Cancer Treat Rep 1982 66: 476–482

    Google Scholar 

  24. Sarosy G, Leyland-Jones B, Soochan P, Cheson BD . The systemic administration of intravenous melphalan J Clin Oncol 1988 6: 1768–1782

    Article  CAS  Google Scholar 

  25. Barlogie B, Alexanian R, Smallwood L, Cheson B, Dixon D, Dicke K, Cabanillas F . Prognostic factors with high-dose melphalan for refractory multiple myeloma Blood 1988 72: 2015–2019

    CAS  PubMed  Google Scholar 

  26. Cunningham D, Paz-Ares L, Gore ME, Malpas J, Hickish T, Nicolson M, Meldrum M, Viner C, Milan S, Selby PJ . High-dose melphalan for multiple myeloma: long-term follow-up data J Clin Oncol 1994 12: 759–763

    Article  CAS  Google Scholar 

  27. Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J . Total therapy with tandem transplants for newly diagnosed multiple myeloma Blood 1999 93: 55–65

    CAS  PubMed  Google Scholar 

  28. Lemoli RM, Fortuna A, Motta MR, Rizzi S, Giudice V, Nanetti A, Martinelli G, Cavo M, Amabile M, Mangianti S, Fogli M, Conte R, Tura S . Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells Blood 1996 87: 1625–1634

    CAS  PubMed  Google Scholar 

  29. Slattery JT, Sanders JE, Buckner RL, Schaffer RL, Lambert KW, Langer FP, Anasetti C, Bensinger WI, Fisher LD, Appelbaum FR . Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics Bone Marrow Transplant 1995 16: 31–42

    CAS  PubMed  Google Scholar 

  30. Moreau P, Milpied N, Mahe B Juge Morineau N, Rapp MJ, Bataille R, Harousseau JL . Melphalan 220mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma Bone Marrow Transplant 1999 23: 1003–1006

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by MURST (TURA), 40% Fondi Ex60% (CAVO).

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Tosi, P., Zamagni, E., Ronconi, S. et al. Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. Leukemia 14, 1310–1313 (2000). https://doi.org/10.1038/sj.leu.2401819

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