TY - JOUR
T1 - Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy
AU - de Botton, S.
AU - Sanz, M. A.
AU - Chevret, S.
AU - Dombret, H.
AU - Martin, G.
AU - Thomas, X.
AU - Mediavilla, J. D.
AU - Recher, C.
AU - Ades, L.
AU - Quesnel, B.
AU - Brault, P.
AU - Fey, M.
AU - Wandt, H.
AU - Machover, D.
AU - Guerci, A.
AU - Maloisel, F.
AU - Stoppa, A. M.
AU - Rayon, C.
AU - Ribera, J. M.
AU - Chomienne, C.
AU - Degos, L.
AU - Fenaux, P.
N1 - Funding Information:
This work was supported by the Programme Hospitalier de Recherche Clinique (CHU Lille), the Association de Recherche contre le Cancer and the Ligue Nationale contre le Cancer (Comité du Nord).
PY - 2006/1/1
Y1 - 2006/1/1
N2 - We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700 -162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARα isoform (P =0.0003) and high WBC counts (≥10 000/mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P=0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (≥10 000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC ≥10000/mm3 at diagnosis remains to be established.
AB - We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700 -162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARα isoform (P =0.0003) and high WBC counts (≥10 000/mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P=0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (≥10 000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC ≥10000/mm3 at diagnosis remains to be established.
KW - Acute promyelocytic leukemia
KW - All-trans retinoic acid
KW - Extramedullary relapse
UR - http://www.scopus.com/inward/record.url?scp=33644976445&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2404006
DO - 10.1038/sj.leu.2404006
M3 - Article
C2 - 16307026
AN - SCOPUS:33644976445
SN - 0887-6924
VL - 20
SP - 35
EP - 41
JO - Leukemia
JF - Leukemia
IS - 1
ER -