Acute promyelocytic leukemia: All-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone

Abstract

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytoge-netic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemo-therapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA. Am. J. Hematol. 60:87-93, 1999.

Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD–positive leukemic cells

“…However, the use of ATRA in combination with traditional chemotherapeutic agents produces the highest sustained remissions rate of any FrenchAmerican-British (FAB) subtype of AML. 40,48 This example suggests that the most effective use of targeted agents in AML may be in combination with standard AML chemotherapy agents.…”

“…However, the use of ATRA in combination with traditional chemotherapeutic agents produces the highest sustained remissions rate of any FrenchAmerican-British (FAB) subtype of AML. 40,48 This example suggests that the most effective use of targeted agents in AML may be in combination with standard AML chemotherapy agents.In our experiments we have shown the feasibility of combining a FLT3 inhibitor, SU11248, with standard AML chemotherapy drugs. SU11248 increased the antiproliferative effects of cytarabine and daunorubicin on FLT3 ITD-containing cell lines.…”

SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase

“…However, the use of ATRA in combination with traditional chemotherapeutic agents produces the highest sustained remissions rate of any FrenchAmerican-British (FAB) subtype of AML. 58,59 In this manner, the targeting of FLT3 in combination with other agents may prove useful in the development of more effective therapy for patients with AML.…”

Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children

“…Therefore, the combination of ATRA and an intensive chemotherapy seemed to be more effective [1]. According to theresults of our previous studies BFM 78-87, relapse rate was low after an intensive multidrug treatment regimen.…”

“…According to our experiences, we recommend a dosage of 25 mg/m 2 per day, an early reduction or interruption of ATRA treatment, and probably most important the use of dexamethasone when symptoms of ATRA toxicity occur [1,10]. The decrease in the early death rate and the prevention of severe ATRA toxicity enabled a further improvement of overall survival of children with APL.…”