TY - JOUR
T1 - Clinical and laboratory evaluation of all-trans retinoic acid modulation of chemotherapy in patients with acute myelogenous leukaemia
AU - Seiter, Karen
AU - Feldman, Eric J.
AU - Dorota Halicka, H.
AU - Deptala, Andrzej
AU - Traganos, Frank
AU - Burke, Harry B.
AU - Hoang, Albert
AU - Goff, Heather
AU - Pozzuoli, Monica
AU - Kancherla, Ramamohana
AU - Darzynkiewicz, Zbigniew
AU - Ahmed, Tauseef
PY - 2000
Y1 - 2000
N2 - All-trans retinoic acid (ATRA) is synergistic with chemotherapy in leukaemia cell lines. We treated 53 patients with newly diagnosed acute myelogenous leukaemia (AML) with high-dose cytarabine-based chemotherapy followed by ATRA. Peripheral blood and bone marrow samples were obtained to study the effect of in vitro exposure to ATRA and to measure apoptosis and bcl-2. The response rate was 72% for patients under age 60 years and 46% for patients aged 60 years or above. There was no difference in the percentage of responding patients, time to recurrence or overall survival for patients receiving chemotherapy with ATRA vs. historical controls receiving chemotherapy without ATRA. After in vitro exposure of day 3 bone marrow samples to ATRA, there was an increase in apoptotic cells in 25% of patient samples compared with samples not exposed to ATRA. Later date of peak apoptosis in peripheral blood and higher percentage of apoptotic cells in bone marrow on day 3 of treatment were associated with lack of clinical response to treatment. Increased bcl-2 in patient samples was associated with shorter time to recurrence and poor cytogenetic risk. The addition of ATRA to chemotherapy did not improve patient outcome. However, evidence of in vitro response to ATRA in 25% of patients suggests that retinoid pathways should be studied further in patients with AML.
AB - All-trans retinoic acid (ATRA) is synergistic with chemotherapy in leukaemia cell lines. We treated 53 patients with newly diagnosed acute myelogenous leukaemia (AML) with high-dose cytarabine-based chemotherapy followed by ATRA. Peripheral blood and bone marrow samples were obtained to study the effect of in vitro exposure to ATRA and to measure apoptosis and bcl-2. The response rate was 72% for patients under age 60 years and 46% for patients aged 60 years or above. There was no difference in the percentage of responding patients, time to recurrence or overall survival for patients receiving chemotherapy with ATRA vs. historical controls receiving chemotherapy without ATRA. After in vitro exposure of day 3 bone marrow samples to ATRA, there was an increase in apoptotic cells in 25% of patient samples compared with samples not exposed to ATRA. Later date of peak apoptosis in peripheral blood and higher percentage of apoptotic cells in bone marrow on day 3 of treatment were associated with lack of clinical response to treatment. Increased bcl-2 in patient samples was associated with shorter time to recurrence and poor cytogenetic risk. The addition of ATRA to chemotherapy did not improve patient outcome. However, evidence of in vitro response to ATRA in 25% of patients suggests that retinoid pathways should be studied further in patients with AML.
KW - Acute myelogenous leukaemia
KW - All-trans retinoid acid
KW - Apoptosis
KW - Bcl- 2
KW - Chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=0033954404&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2000.01804.x
DO - 10.1046/j.1365-2141.2000.01804.x
M3 - Article
C2 - 10651722
AN - SCOPUS:0033954404
SN - 0007-1048
VL - 108
SP - 40
EP - 47
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -