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5 DEDICATORIA A MI QUERIDA HIJA EVITA A MI ESPOSA EVA A MIS PADRES: VICTOR Y ROSA A MI MAESTRO JORGE CASTILLO MOTORES DE MI PROGRESO 1

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7 ITRODUCCIÓ: Mieloma multiple es una de las neoplasias hematológicas más frecuentes. Durante los últimos años los avances en el diagnóstico y estadiaje han sido promisorios, sin embargo con el objetivo de prolongar la sobrevida total (ST), los distintos esquemas de quimioterapia de inducción (QTI) no han logrado resultados significativamente favorables. Para evaluar la respuesta a la QTI ya sea con Melfalán-Prednisona (MP) o Quimioterapias Combinadas (QTC) se planteo un estudio retrospectivo. MATERIAL Y MÉTODOS: Se estudiaron un total de 161 casos de mieloma multiple diagnosticada en el Hospital acional Edgardo Rebagliati Martins - EsSalud, evaluándose diferentes factores clínicos, laboratoriales y terapeúticos al debut, realizando el análisis estratificados según factores de riesgo mediante la elaboración de las curvas de sobrevida de Kaplan Meier y la determinación del Log Rank con p<0,05 para definir significancia estadística. También se compararon el tiempo promedio de respuesta en fase plateau mediante el test de Barlett y el Test de AOVA, considerándose como estadísticamente significativo al F con p<0,05con el estudio de las diferencias en las tasas de respuestas obtenidas. RESULTADOS: La ST promedio fue 43,19 meses, no habiendo diferencia significativa entre los porcentajes de remisión completa, parcial y objetiva logradas por la QTI ya sea MP ó QTC. o existió diferencia en la duración de la fase plateau en el grupo de MP vs. QTC (22,5 m vs m; F=1,122 ; p=0,293) Algunos factores al diagnóstico que se relaciona con mayor ST fueron: edad menor de 65 años (Log rank 2,75 ; p=0,0973), creatinina menor de 2 mg/dl (Log rank 5,92 ; p=0,0149), albumina menor de 3 g/dl (Log rank 11,71 ; p=0,0006), ), Beta 2 microglobulina <=6 mg/dl (Log rank 5,16 ; p=0,0231), estadío clínico IIA (Log rank 17,03 ; p=0,0007) y QTI con MP (Log rank 10,87 ; p=0,0010). Al evaluar si existen diferencias en la ST, al iniciar en los diferentes grupos estratificados con QTI ya sea con MP o QTC, se observó mayor ST al inducir con MP en pacientes: mayores de 65 años(log Rank 11,32 ; p=0,0008), sexo masculino (Log Rank 12,59 ; p=0,0004), hipoalbuminemia (Log Rank 5,26 ; p=0,0218), proteinuria > 150 mg/dl (Log Rank 6,12 ; p=0,0134), LDH normal (Log Rank 6,65 ; p=0,0099), bajo porcentaje tumoral en médula ósea (Log Rank 5,39 ; p=0,0202),ausencia de Bence Jones (Log Rank 16,35 ; p=0,0001), proteina M G Lambda (Log Rank 7,80 ; p=0,0052), estadío clínico III (Log Rank 6,71 ; p=0,0096). La fase plateau fue posible de evaluar en 66 pacientes (53 con QTI de MP y 13 con QTI de QTC), observándose promedios de y meses respectivamente que no ofrecen diferencias estadísticamente importantes (F=1,122 ; p=0,293) COCLUSIOES:o se ha logrado incrementar la ST al incorporar QTC en la inducción; observándose que la QTI con MP muestras mayor ST, existiendo algunos factores catalogados como de alto y bajo riesgo al diagnóstico que se relacionan con mayor margen de ST al manejarlas con MP y que son precisos de valorar antes de iniciar la terapia. 3

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35 Barlogie B, Epstein J, Selvanayagam, et a Plasma cell myeloma: ew biological insights and advances in therapy.blood 73: : 1989 Vacca A., Frigeri et al.microvessel overexpression of aquaporin 1 parallels bone marrow angiogenesis in patients with active multiple myeloma.british JournalHaematology 113: , 2001 Greenlee RT, Hill et al. Cancer Statistic 2001CA Cancer J Clinical 51: 15-36, Jesús F. San Miguel, Joan Blade C, Ramón García-Sanz.Treatment of multiple myeloma Haemotologica 84: 36-58: 1999 Alexanian R, Haut A, Khan AU, et al Treatmente for multiple myeloma: combination chemotherapy with different melphalan dose regimens. Journal of the American Medical Association 208: : 1969 Cornelissen JJ, Sonneveld P, et al. MDR-1 expresion and response to vincristine, doxorrubicin, and dexamethasone chemoterapy in multiple myeloma refractory to alkilating agents. Journal of Clinical Oncology 12: : 1994 Vesole David H, Croley J, Catchatourian R, et al. High dose melphalan with autotrasplantation for Refractory multiple myeloma. Journal of Clinical Oncology 17: : Durie BG, Dixon DO, et al. Improved surviaval duration with combination chemotherapy inducction for multiple myeloma: a Southwest Oncology Group Study. Journal of Clinical Oncology 4: :

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37 therapy for multiple myeloma: a CALGB study. Journal of Clinical Oncology 4: : Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trial. Journal of Clinical Oncology 10: : Myeloma Trialist Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. Journal of Clinical Oncology Vol 16, , 1998 Alexanian R, Gehan A, Haut A, Saiki J, Weick J. Unmaintained remissions in multiple myeloma. Blood 51: : 1978 Cohen HJ, Bartolucci AA, Forman WB, Silberman HR. Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment. Journal of Clinical Oncology 4: : Salmon SE. Crowley JJ, et al. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study Journal of Clinical Oncology 16: : 1998 Berenson JR, Lichtenstein A, et al. Long-term pamidronate treatment of advanced multiple myeoloma patients reduces skeletal events. Myeloma Aredia Study Group. Journal of Clinical Oncology 16: : 1998 Salmon SE. Crowley JJ, et al. Combination chemotherapy, glucocorticoids and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group Study. Journal of Clinical Oncology 12: : 1994 Cooper MR, Dear K, et ala randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study. Journal of Clinical Oncology 11: : 1993 Peest D, Bladé J, et al. Cytokine therapy in multiple myeloma. British Journal of Haematology 94: , Salmón SE, Haut A, et al.alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study. Journal of Clinical Oncology 1: : Sonneveld P, Schoester M, et al. Clinical modulation of multidrug resistance in multiple myeloma: effect of cyclosporine on resistant tumor cells. Journal of Clinical Oncology 12: : 1994 Sonneveld P, Durie BGM, Lokhorst HM. Modulation of multidrug-resistant myeloma by cyclosporin. Lancet 340: 255-9: 1992 Rostom AY, O Cathail SM, et al. Systemic irradiation in multiple myeloma: a report on nineteeen cases. British Journal of Haematology 96: 746-8, 1997 Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. ew England Journal of Medicine 334: : 1996 Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interpheron alpha-2b in patients with multiple myeloma responding to conventional 33

38 ! " # $ " % &" ' ( # $ )" % "&" (" ) &$" ( " &" & &* "( +( " ", (" induction chemotherapy. ew England Journal of Medicine 322: : 1990 Bart Barlogie, MD, Ph D. Intensive therapy and steam cell transplants in multiple myeloma ew elements in the diagnosis and treatment of multiple myeloma, San Diego 1997, California. Blade J. San Miguel JF, et al. Survival of multiple myeloma patients who are potential candidates for early high dose therapy intensification autotransplatation and who were conventionally treated. Journal of Clinical Oncology 14: : 1996 Gahrton G, Tura S, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. Journal of Clinical Oncology 13: : 1995 Blade J, San Miguel JF, et al. Surviva of multiple myeloma patients who are potencial candidates for early high-dose therapy intensification/autotransplantation and who were conventionally treated. Journal of Clinical Oncology 14: :

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