Acute promyelocytic leukemia (APL) is a specific subtype of acute leukemias characterized by t(15;17) chromosomal translation. Although APL is treatable with ...
Leukemia (2000) 14, 1153–1160 2000 Macmillan Publishers Ltd All rights reserved 0887-6924/00 $15.00 www.nature.com/leu
CORRESPONDENCE Interferon may reduce minimal residual disease of acute promyelocytic leukemia
TO THE EDITOR Acute promyelocytic leukemia (APL) is a specific subtype of acute leukemias characterized by t(15;17) chromosomal translation. Although APL is treatable with the vitamin A derivative ALL-trans retinoic acid (ATRA), during treatment ATRA resistance may develop.1,2 In cases of ATRA resistance arsenic therapy and/or bone marrow transplantation can offer further possibilities for treatment.3 As an alternative treatment of ATRA resistance, interferon (IF) therapy has been suggested by in vitro and in vivo experiments.4,5 In this report we describe a case of APL where IF therapy reduced the minimal residual disease. A 21-year-old female patient was admitted to the Hematological Department of Internal Medicine, Kaposi Mo´r Hospital, Kaposva´r, Hungary in February 1995 for palor, fatigue and bone pain. The morphological evaluation of the bone marrow smears revealed M2 subtype of acute myeloid leukemia. At the time of diagnosis cytogenetic evaluation of the leukemic cells was initiated. Ten days following the morphologic diagnosis, the cytogenetic results revealed a t(15;17)(q22;q11) translocation. Induction therapy was then started with the 7+3 treatment (daunorubicin 45 mg/m2 1–3, cytosine arabinoside 200 mg/m2 1–7). Complete hematological remission was observed on the 21st day of treatment. Following the induction treatment three courses of HIDAC (cytosine arabinoside 2 × 3 g 1, 3, 5) were given. Cytogenetic and molecular genetic remissions were observed according to Biondi et al.6 Cytogenetic remission was achieved after the first, while molecular genetic remission was detected after the second post-induction course. After 14 months of complete remission a molecular relapse (0.1%) was observed followed 1 month later by complete hematological relapse. Two courses of AIDA (ATRA 45 mg/m2 1–30, idarubicin 12 mg/m2 2, 4, 6, 8) treatment started at this time resulted in molecular remission (0.0001%), however, 3 months later molecular relapse (0.1%) occurred, which suggested that ATRA resistance had developed. Unfortunately, bone marrow transplantation was not feasible due to lack of a suitable HLA identical donor, while arsenic therapy was not available. Based on the results of Koller et al5 interferon alfa-2a was initiated at 3 MU/day doses in order to eliminate ATRA resistance. At the end of the fourth month of treatment less than 0.0001% of chimera could be detected, against 0.01% at the end of the first month of treatment with interferon. Because of molecular remission IF therapy was suspended. Following 2 months of remission, molecular relapse (0.01%) developed, IF therapy was resumed and resulted in molecular remission (⬍0.0001%) within 2 months. This time severe pancytopenia developed, therefore IF therapy was replaced by supportive treatment. A month later hematologicalrelapse developed. ATRA treatment was initiated but the patient died after 6 h of treatment because of adult respiratory distress syndrome.
Correspondence: M Egyed; Fax: 36 82 411 535 Received 18 February 1999; accepted 26 April 1999
To the best of our knowledge this case report provides the first evidence that IF therapy may reduce the minimal residual disease in cases of ATRA-resistant APL. Based on these results, it would be worthwhile to treat larger numbers of patients with IF at the stage of ATRA resistance of the disease to see whether IF treatment is useful in reaching hematological remission of APL.
M Egyed1 G Rumi1 B Boros1 P Pa´ldi-Haris2 J Fo¨ldi2
1
Hematological Department of Internal Medicine Kaposi Mo´r Hospital, Kaposva´r; and 2 Department of Molecular Genetics National Institution of Hematology, Budapest, Hungary
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