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Effect of all-trans-retinoic acid alone or in combination with chemotherapy in newly diagnosed acute promyelocytic leukaemia

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Abstract

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans-retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 109/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 109/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 109/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 109/l). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard ′3+7′ chemotherapy (DNR 45 mg m-2,1 -3 days, ARA-C 200 mg m-2,1-7 days) followed by two courses of standard ′2+5′ chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).

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Authors and Affiliations

  1. Institute of Hematology, Clinical Center of Serbia, 11000 Belgrade, ul. Dr Koste Todorovića br. 2, Yugoslavia

    Milica D. Čolović, Gradimir M. Janković, Ivo Elezović, Ana Vidović, Jelena S. Bila & Angelina Novak

  2. Institute of Statistics, Medical Faculty of Belgrade, Yugoslavia

    Dragan Babić

Authors
  1. Milica D. Čolović
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  2. Gradimir M. Janković
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  3. Ivo Elezović
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  4. Ana Vidović
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  5. Jelena S. Bila
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  6. Angelina Novak
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  7. Dragan Babić
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Čolović, M.D., Janković, G.M., Elezović, I. et al. Effect of all-trans-retinoic acid alone or in combination with chemotherapy in newly diagnosed acute promyelocytic leukaemia. Med Oncol 14, 65–72 (1997). https://doi.org/10.1007/BF02990950

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