Trasplante autólogo de progenitores hematopoyéticos en pacientes con mieloma múltiple
Análisis de factores pronósticos y sobrevida. Experiencia del Hospital Británico
Palabras clave:
TRASPLANTE DE CÉLULAS MADRE HEMATOPOYÉTICAS, TRASPLANTE AUTÓLOGO, MIELOMA MÚLTIPLEResumen
Introducción: el trasplante autólogo de progenitores hematopoyéticos (TAPH) es considerado estándar en el tratamiento de primera línea en pacientes con mieloma múltiple (MM) menores de 65 años.
Objetivo:analizar la sobrevida global (SG) y sobrevida libre de eventos (SLEv) de los pacientes con MM trasplantados en el Hospital Británico.
Material y método: se realizó un estudio retrospectivo de los pacientes que recibieron un primer TAPH.
Resultados:entre el 1º de julio de 1999 y el 30 de junio de 2010 se realizaron 56 TAPH a 48 pacientes con MM. Del análisis de los pacientes al primer TAPH, 46% eran mujeres y 54% hombres. La mediana de edad fue de 54 años (32-65 años). El 73% eran IgG, 17% IgA y 10% de cadenas livianas. El 60,4% logró una RC/nRC (RC, RC no confirmada y VGPR) posTAPH. Con una media de seguimiento de 58,6 meses (5,84-186,56), la mediana de SG fue de 121,8 meses (IC 95%: 70,1-173,54 meses). No se hallaron diferencias significativas en SG entre los pacientes que lograron RC/nRC posTAPH y quienes no lo lograron (log Rank p=0,162). La mediana de SLEv fue de 56 meses (IC 95%: 42,2-70,4 meses).
Conclusiones: el TAPH es una herramienta fundamental en el tratamiento de los pacientes con MM y es un procedimiento seguro en la Unidad de Hematología del Hospital Británico.
Citas
(2) Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348(19): 1875-83.
(3) Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood 2004; 104(10): 3052-7.
(4) Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña J, et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish Cooperative Group PETHEMA. Blood 2005; 106(12): 3755-9.
(5) Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, et al. High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005; 23(36): 9227-33.
(6) Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup trial S9321. J. Clin Oncol 2006; 24(6): 929-36.
(7) Koreth J, Cutler CS, Djulbegovic B, Behl R, Schlossman RL, Munshi NC, et al. High dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: a systematic review and metaanalysis of randomized controlled trials. Biol Blood Marrow Transplant 2007; 13(2): 183-96.
(8) Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, et al. Intergroupe Francophone du Myélome. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 2002; 99(3): 731-5.
(9) Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349(26): 2495-502.
(10) Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 2007; 25(17): 2434-41.
(11) Crawley C, Iacobelli S, Björkstrand B, Apperley JF, Niederwieser D, et al. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007; 109(8): 3588-94.
(12) Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: Up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998; 92: 3131-6.
(13) Facon T, Mary JY, Harousseau JL. Front-line or rescue autologous bone marrow transplantation (ABMT) following a first course of high dose melphalan (HDM) in multiple myeloma (MM). Preliminary results of a prospective randomized trial (CIAM) protocol. Blood 1996; 88(1): 685a.
(14) Barlogie B, Kyle R, Anderson K. Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m2 1 TBI 12 Gy autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: results of intergroup Trial S9321. Blood 2003; 102: 42a.
(15) Alexanian R, Weber D, Giralt S, Dimopoulos M, Delasalle K, Smith T, et al. Impact of complete remission with intensive therapy in patients with responsive multiple myeloma. Bone Marrow Transplant 2001; 27(10): 1037-43.
(16) Lahuerta JJ, Mateos MV, Martínez-López J, Rosiñol L, Sureda A, de la Rubia J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol 2008; 26(35): 5775-82.
(17) van de Velde HJ, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M. Complete response correlates with long-term survival and progression free survival in high-dose therapy in multiple myeloma. Haematologica 2007; 92(10): 1399-406.
(18) Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20(9): 1467-73.
(19) Center for International Blood & Marrow Transplant Research. Disponible en: http://www.cibmtr.org/pages/index.aspx. Consulta: 26/5/2011.
(20) Papanikolaou X, Maltezas D, Repousis P, Athanassopoulos A, Alexia S, Megalakaki K, et al. High dose chemotherapy and autologous stem cell transplantation in patients with multiple myeloma: the experience of a single haematological unit. J BUON 2008; 13(2): 193-7.
(21) Majolino I, Vignetti M, Meloni G, Vegna ML, Scimè R, Tringali S, et al. Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Haematologica 1999; 84(9): 844-52.
(22) Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005; 106(1): 35-9.
(23) Cavo M, Di Raimondo F, Zamagni E, Patriarca F, Tacchetti P, Casulli AF, et al. Short-Term Thalidomide Incorporated Into Double Autologous Stem-Cell Transplantation Improves Outcomes in Comparison With Double Autotransplantation for Multiple Myeloma. J Clin Oncol 2009; 27(30): 5001-7.
(24) Macro M, Divine M, Uzunhan Y. Dexamethasone + Thalidomide (Dex/Thal) compared to VAD as a Pre-Transplant Treatment in Newly Diagnosed Multiple Myeloma (MM): A Randomized Trial.. Blood 2006; 108: 22a.
(25) Lenhoff S, Hjorth M, Turesson I, Westin J, Gimsing P, Wislöff F, et al. Intensive therapy for multiple myeloma in patients younger than 60 years: Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation. Haematologica 2006; 91(9): 1228-33.
(26) Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant 2009; 15(4): 463-70.
(27) Harousseau JL, Avet-Loiseau H, Attal M, Charbonnel C, Garban F, Hulin C, et al. Achievement of at Least Very Good Partial Response Is a Simple and Robust Prognostic Factor in Patients With Multiple Myeloma Treated With High-Dose Therapy: Long-Term Analysis of the IFM 99-02 and 99-04 Trials. J Clin Oncol 2009; 27(34): 5720-6.