Clinical and laboratory evaluation of all‐trans retinoic acid modulation of chemotherapy in patients with acute myelogenous leukaemia
- 1 January 2000
- journal article
- clinical trial
- Published by Wiley in British Journal of Haematology
- Vol. 108 (1) , 40-47
- https://doi.org/10.1046/j.1365-2141.2000.01804.x
Abstract
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.Keywords
This publication has 11 references indexed in Scilit:
- Phase II Evaluation of a High-Dose Mitoxantrone Based Induction Regimen in Untreated Adults with Acute Myeloid LeukemiaLeukemia & Lymphoma, 2000
- Randomized Phase II Study of Fludarabine + Cytosine Arabinoside + Idarubicin ± All-Trans Retinoic Acid ± Granulocyte Colony-Stimulating Factor in Poor Prognosis Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic SyndromeBlood, 1999
- Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormalityLeukemia, 1999
- Phosphorylation of BCL-2 After Exposure of Human Leukemic Cells to Retinoic AcidBlood, 1998
- High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemiaAnnals of Oncology, 1998
- A randomized trial of high- vs standard-dose mitoxantrone with cytarabine in elderly patients with acute myeloid leukemiaLeukemia, 1997
- Down‐regulation of bcl‐2 in AML blasts by all‐trans retinoic acid and its relationship to CD34 antigen expressionBritish Journal of Haematology, 1996
- Intensive Postremission Chemotherapy in Adults with Acute Myeloid LeukemiaNew England Journal of Medicine, 1994
- High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapyBlood, 1993
- Use of differentiation inducing agents in the myelodysplastic syndrome and acute non‐lymphocytic leukemiaAmerican Journal of Hematology, 1988