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161. Differentiation therapy with interferon-alpha plus low-dose cytarabine in acute monoblastic leukemia patients
160. All-&ans retinoic acid (ATRA) and granulocyte colony-stimulating the treatment of myelodysplastic syndromes (MDS): a pilot study A Ganser’,
OG Ottmann’, Hiddemann3, D Hoelzer’
K Kolbe’,
A Maurer I, S Elsner’,
‘Depts of Hematology of the Universities of FrankfurtlMainz;
G Geissler’,
‘Main;
factor (G-CSF) in
C Schardt’,
R Reutzel’,
W
3Gdttingen, Germany
Differentiation induction therapy has been studied in patients (pts) with myelodysplastic syndromes in various forms, eg treatment with interferons, retinoic acid, vitamin D, low-dose area-C. colony-stimulating factors (CSF). Since ATRA and G-CSF synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with MDS, especially with refractory anemia without blast cells in the bone marrow. ATRA was given at 45 mg/m2/day po from week 1-12 and G-CSF at 5 pg/kg/day SQ from week 5-12 to be adjusted to the neutrophil count (ANC). A total of 11 patients (median age: 66 years; range: 57-71) were treated, eight males and three females. During initial ATRA therapy, ANC increased in three patients, platelet count (pits) in four patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, plts increased in three out of ten evaluable patients but decreased in one patient. Improvement of impaired erythropoiesis was not seen. In the bone marrow, the myeloid-erythroid ratio increased. but not the maturation index of myeloid cells. Cytogenetic analysis demonstrated the persistence of the abnormal clones in all patients. Adverse effects included dermatitis and cheilosis in most patients and a drop in plt counts in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well colerated in n&t patients leading to normalization of ANC in most and of pits in a substantial portion of patients.
161. Differentiation therapy with interferon-alpha oblastic leukemia patients HT Hassan’, HR Maurer2* IDepartment of Haematology. Medical Freie Vnbersitdt Berlin, Germany
Research
plus low-dose cytarabine in acute mon-
Institute, Alexandria
University, Egypt; 21nstitut fur Pharmazie,
As acute monoblastic leukemia (AMoL) is a malignant disease in which neither conventional intensive chemotherapy nor bone marrow transplantation was beneficial, it is justified in this disease to evaluate the efficacy of interferon-alpha (IFNalpha) that seems promising on the basis of a possible role for its juxta-positioned genes in the pathogenesis of the differentiation defect in scme AMoL patients, of its regulatory effect in monocyte differentiation and of its success in the treatment of chronic leukemias. Six children with untreated primary AMoL (median age 9.8 years: range, 7.5-13) were treated with recombinant human IFN-alpha 2b (3 million U/m*/day SC three times weekly) plus low dose cytarabine (10mgfm2/day SC daily) for 21 days with or without hydroxyurea [HU] (50 mgfkglday orally daily only for patients with WC counts of 2 50 x 109/1) for 10 days in a clinical pilot study. Prophylactic paracetamol, antibiotics and allopurine were given orally daily to suppress concomitant influenza1 symptoms, fever and prevent infections and urate nephropathy. After two treatment courses, 4 patients achieved complete remission and 2 had partial remission. HU was also, effective in reducing the leukemic mass and preventing leukostasis in the patients with V%C count of 2 50 x 109/l. Therapy was well tolerated, with thrombocytopenia comprising the prominant side effect which required frequent platelet transfusions (median: 4 units per treatment course, range: 2-7). Upon the achievement of complete remission, CNS prophylaxis with cranial irradiation was administered followed by maintenance therapy with 6-thioguanine plus hydroxyurea for 7 days every three weeks. For follow-up durations of nine months or more, the four patients have sustained ongoing complete remission. These promising results warrant confirmation and randomiscd comparison with established regimens to determine any survival advantage in large clinical studies for leukemia patients aged 2 6 years. Both interferon-alpha [2] and low dose cytarabine [ 1] induce in vitro differentiation of human acute monoblastic leukemia cells, therefore it would be interesting to investigate any possible in vivo differentiation in response to the treatment with their combination in acute monoblastic leukemia patients using the bormodeoxyuridine labelling and/or premature condensed chromosome analyses. 1 Hassan HT et al (1991) Eur J Chin Pharmacol 41, 531 2 Hassan HT. Maurer HR (1991) Chemotherapy 37, 441 3 Hassan HT. Maurer HR (1991) Med Res Sci 19, 195
OG Ottmann’, Hiddemann3, D Hoelzer’
K Kolbe’,
A Maurer I, S Elsner’,
‘Depts of Hematology of the Universities of FrankfurtlMainz;
G Geissler’,
‘Main;
factor (G-CSF) in
C Schardt’,
R Reutzel’,
W
3Gdttingen, Germany
Differentiation induction therapy has been studied in patients (pts) with myelodysplastic syndromes in various forms, eg treatment with interferons, retinoic acid, vitamin D, low-dose area-C. colony-stimulating factors (CSF). Since ATRA and G-CSF synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with MDS, especially with refractory anemia without blast cells in the bone marrow. ATRA was given at 45 mg/m2/day po from week 1-12 and G-CSF at 5 pg/kg/day SQ from week 5-12 to be adjusted to the neutrophil count (ANC). A total of 11 patients (median age: 66 years; range: 57-71) were treated, eight males and three females. During initial ATRA therapy, ANC increased in three patients, platelet count (pits) in four patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, plts increased in three out of ten evaluable patients but decreased in one patient. Improvement of impaired erythropoiesis was not seen. In the bone marrow, the myeloid-erythroid ratio increased. but not the maturation index of myeloid cells. Cytogenetic analysis demonstrated the persistence of the abnormal clones in all patients. Adverse effects included dermatitis and cheilosis in most patients and a drop in plt counts in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well colerated in n&t patients leading to normalization of ANC in most and of pits in a substantial portion of patients.
161. Differentiation therapy with interferon-alpha oblastic leukemia patients HT Hassan’, HR Maurer2* IDepartment of Haematology. Medical Freie Vnbersitdt Berlin, Germany
Research
plus low-dose cytarabine in acute mon-
Institute, Alexandria
University, Egypt; 21nstitut fur Pharmazie,
As acute monoblastic leukemia (AMoL) is a malignant disease in which neither conventional intensive chemotherapy nor bone marrow transplantation was beneficial, it is justified in this disease to evaluate the efficacy of interferon-alpha (IFNalpha) that seems promising on the basis of a possible role for its juxta-positioned genes in the pathogenesis of the differentiation defect in scme AMoL patients, of its regulatory effect in monocyte differentiation and of its success in the treatment of chronic leukemias. Six children with untreated primary AMoL (median age 9.8 years: range, 7.5-13) were treated with recombinant human IFN-alpha 2b (3 million U/m*/day SC three times weekly) plus low dose cytarabine (10mgfm2/day SC daily) for 21 days with or without hydroxyurea [HU] (50 mgfkglday orally daily only for patients with WC counts of 2 50 x 109/1) for 10 days in a clinical pilot study. Prophylactic paracetamol, antibiotics and allopurine were given orally daily to suppress concomitant influenza1 symptoms, fever and prevent infections and urate nephropathy. After two treatment courses, 4 patients achieved complete remission and 2 had partial remission. HU was also, effective in reducing the leukemic mass and preventing leukostasis in the patients with V%C count of 2 50 x 109/l. Therapy was well tolerated, with thrombocytopenia comprising the prominant side effect which required frequent platelet transfusions (median: 4 units per treatment course, range: 2-7). Upon the achievement of complete remission, CNS prophylaxis with cranial irradiation was administered followed by maintenance therapy with 6-thioguanine plus hydroxyurea for 7 days every three weeks. For follow-up durations of nine months or more, the four patients have sustained ongoing complete remission. These promising results warrant confirmation and randomiscd comparison with established regimens to determine any survival advantage in large clinical studies for leukemia patients aged 2 6 years. Both interferon-alpha [2] and low dose cytarabine [ 1] induce in vitro differentiation of human acute monoblastic leukemia cells, therefore it would be interesting to investigate any possible in vivo differentiation in response to the treatment with their combination in acute monoblastic leukemia patients using the bormodeoxyuridine labelling and/or premature condensed chromosome analyses. 1 Hassan HT et al (1991) Eur J Chin Pharmacol 41, 531 2 Hassan HT. Maurer HR (1991) Chemotherapy 37, 441 3 Hassan HT. Maurer HR (1991) Med Res Sci 19, 195