Gemcitabine‐associated thrombotic microangiopathy

Abstract

BACKGROUNDGemcitabine‐associated thrombotic microangiopathy (TMA) is believed to be very rare, with an estimated incidence rate of 0.015%. Indications for gemcitabine are expanding, and comprehensive characterization of this complication is therefore important.METHODSThe authors performed a retrospective chart review of all cases with gemcitabine‐associated TMA diagnosed at Partners Healthcare System (Boston, MA) between January 1997 and February 2002.RESULTSNine patients with gemcitabine‐associated TMA were identified. Diagnosis was aided by clinical and laboratory features. Renal biopsy confirmed the diagnosis in two patients. The cumulative incidence of gemcitabine‐associated TMA was 0.31% (8 cases among 2586 patients) when only the 8 patients with TMA who were treated at clinics associated with the current study were considered (1 patient with a TMA syndrome was transferred from another institution). The median patient age was 53 years, and the median time to development of a TMA syndrome after the initiation of gemcitabine was 8 months (range, 3–18 months), with a cumulative dose ranging from 9 to 56 g/m2. New or exacerbated hypertension was a prominent feature in 7 of 9 patients and preceded the clinical diagnosis by 0.5–10 weeks. Treatment of TMA included discontinuation of gemcitabine, antihypertensive therapy, plasma exchange, and dialysis. Outcomes are known for all nine patients. Six patients remain alive, whereas three have died of disease progression. No patient died as a direct result of TMA, but two developed kidney failure requiring dialysis, and one developed chronic renal insufficiency.CONCLUSIONSIn the current series, the largest single‐institution study to date, the incidence of gemcitabine‐associated TMA was higher than previously reported (0.31% vs. 0.015%). Seven of nine patients developed new or exacerbated hypertension, which could be a useful early identifier of patients with gemcitabine‐associated TMA syndromes. Cancer 2004. © 2004 American Cancer Society.

Síndrome hemolítico-urémico asociado al uso de gemcitabina: Caso clínico

“…Se ha utilizado también en cáncer pulmonar de células no pequeñas, linfoma, cáncer de ovario, mama, hígado, vía biliar y vejiga [3][4][5]14,19 .…”

“…El SHU asociado a GEM tiene una baja incidencia, varía entre 0,008% y 2,2% de los pacientes tratados con la droga 3,[10][11][12][13]22 . Se asocia frecuentemente a falla renal con necesidad de diálisis y tiene elevada mortalidad 11,14,21,22 .…”

“…En el último control, 10 sem después de la última dosis de GEM, la hemoglobina fue 12,3 g/dL, plaquetas 147.000 mm 3 , leucocitos 4.700 mm 3 , creatinina sérica 1,18 mg/dl, clearance de creatinina 85 ml/min/1,73 m 2 y LDH normal. El paciente continuó recibiendo olmesartán como terapia antihipertensiva originada por el daño renal por GEM.…”

“…Existen diversas etiologías: infecciones entéricas, formas familiares, enfermedades autoinmunes, trasplante de médula ósea, embarazo, neoplasias diseminadas, infecciones por VIH y drogas [3][4][5][6][7][8][9][10] . De estas últimas se han descrito casos asociados al uso de ciclosporina, tacrolimus, ticlopidina, alfa interferón, quinina y a drogas oncológicas como mitomicina C, cisplatino, bleomicina, 5 fluoracilo, adriamicina, carboplatino y otras [3][4][5][6]10 .…”

“…En los últimos años se han comunicado en forma creciente casos de SHU asociados al uso de gemcitabina (GEM), droga introducida en 1996 para el tratamiento del cáncer pancreático irresecable o metastásico y que ha tenido un amplio uso [3][4][5][6][7][8][9][10][11][16][17][18][19][20][21][22][23][24] . Se ha utilizado también en cáncer pulmonar de células no pequeñas, linfoma, cáncer de ovario, mama, hígado, vía biliar y vejiga [3][4][5]14,19 .…”