Hypoplastic acute myeloid leukaemia with 7 years of complete remission by low‐dose cytosine arabinoside therapy alone

To the Editor: Low-dose cytosine arabinoside (LDAC) regimens have been applied to some types of acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS), and high response rates have been reported especially in patients with hypoplastic AML (1-4). However, remission duration was brief in most cases. There have been few reports with long-term follow-up over 5 years. We report a patient with hypoplastic AML who achieved CR with LDAC regimen which has been maintained for 7 years with more than 5 years maintenance courses of LDAC. This case was reported previously as hypoplastic AML with inv( 16)(5). We present this case as the longest CR of hypoplastic AML so far reported. A 74-year-old woman was admitted to Shimabara Prefectural Hospital because of anaemia and neutropenia and was referred to our hospital for further evaluation on April 30, 1987. The patient had been treated with radioisotope therapy using 1311 for Grave’s disease at age 64. Family history was unremarkable. Physical examination revealed only anaemia. Haematological findings at the time of diagnosis were as follows: haemoglobin 9.6 g/dl, WBC 1.85 x 109/1 with neutrophils 13%, monocytes 19%, eosinophils 1 %, no blast cells, lymphocytes 67 %, and platelets 150 x 109/l. Examination of the bone marrow showed 50,000 nucleated cells/$ with 20.0% blasts, 21.2% monocytes, 12.0% eosinophils, 5.4% maturing neutrophils, 2 1 .O% lymphocytes and 17.2% erythroblasts. The blasts had Auer rods, and the eosinophils had coarse basophilic granules in their cytoplasm that were positive for chloroacetate esterase and periodic acid-Schiff reactions. A biopsy of the iliac bone marrow showed severe hypoplasia with 32% cellular marrow. Cytogenetic examination revealed 46,XX,inv( 16)(p 13q22) and 46,XX in 4 and 8 metaphase preparations, respectively. Serum chemistry was normal with the exception of elevated lactic dehydrogenase 547 mU/dl, and lysozyme was within normal limits (5.3 pg/ml). After one course of low-dose Ara-C (10 mg/day continuous infusion for 2 1 days), the patient achieved CR in June 1987. She was treated with two more courses of the same regimen at 3-week intervals as consolidation therapy, and was maintained on lowdose Ara-C (20 mg once a day for 14-21 days by subcutaneous injection) every 3-5 months for 64 months. She has been under observaton without therapy since October 1992, maintaining CR without relapse for 87 months. After achieving CR, the bone marrow cellularity became almost normal and cytogenetic analysis showed only normal karyotypes. With regard to the toxicity of the low-dose Ara-C regimen, bone marrow suppression was regularly observed after each course, but red cell and platelet transfusions were not required. The patient performed the maintenance therapy by self-injection with the help of her family, but there was no remarkable complications or side effects. Low-dose Ara-C regimens have been applied for some types of AML. CR rates in overall AML were approximately 30% (6-8). However, relatively high CR rates (60-80%) were reported in hypocellular AML (1-4). Hypocellular or hypoplastic AML is characterized by hypocellular bone marrow and less aggressive clinical course and affects mainly elderly patients. The good response to LDAC observed in hypoplastic cases may be explained by slower cell kinetics and lower leukaemic mass. With regard to CR duration, many reports have described that CR achieved with LDAC is relatively short; the median duration of CR was between 5 to 10 months (6-8). There is still no consensus concerning appropriate types of maintenance therapy after achieving CR with LDAC. It was reported that a repeated LDAC regimen provided lasting PR similar to the duraton of CR(8), or obtained 2nd or 3rd CR(3). Therefore, therapy-dependent CR may be maintained with repeated LDAC treatment in some cases. It is not clear for how long the maintenance therapy should be continued. We feel that not only the high sensitivity of leukaemic cells to LDAC but