S-HAM Salvage Therapy of Relapsed and Refractory AML Followed by Interleukin 2 Postremission Therapy
A preceding study of the German AML Cooperative Group with an age adjusted randomized comparison of high-dose versus intermediate-dose Cytosine Arabinoside (AraC) as part of the S-HAM protocol indicated a significantly higher antileukemic activity of AraC at a dose of 3.0 vs. 1.0 g/m2 per single dose predominantly in patients with early relapse and second or subsequent recurrence of disease but also an increased rate of early deaths. Based on these results the current study aimed at taking advantage of the high antineoplastic activity of high dose AraC but to reduce the associated infectious complications by the posttherapeutic application of G-CSF. AraC dose was adjusted to disease status and age in that patients below 60 years of age with early relapse and second or subsequent recurrence received AraC at a dose of 3.0 g/m2 while later first relapses and older patients were treated with AraC 1.0 g/m2. Immediately after the end of S-HAM G-SCF was applied at a dose of 5 ug/kg until neutrophil recovery. Patients achieving a complete remission underwent randomization for postremission therapy with Interleukin 2 (IL2) 18 × 106 U/m2/d over 5 days by cont. infusion or observation only. IL2 therapy was repeated at 4 week intervals. At the present time 53 patients have been entered into the study and 38 are evaluable for response and toxicity. 22 cases (58%) obtained a CR, 9 patients (24%) were NR and 7 cases (18%) died during the first six weeks (early deaths). Neutrophil recovery occured at a median of 28 days and was significantly shorter as compared to the preceding S-HAM therapy without G-CSF support. 8 patients have been randomized for IL2 postremission therapy. These results indicate a significant improvement of remission rate and a reduction of lethal complications by G-CSF administration as compared to the historic control. Further recruitment and a longer observation time are needed to substantiate these findings and to assess the impact of IL2 on remission duration.
KeywordsToxicity Lymphoma Leukemia Diarrhea Glucocorticoid
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- 1.Gale RP, Foon KA: Therapy of acute myelogenous leukemia. Semin Hematol 2224: 40–54, 1987Google Scholar
- 3.Hiddemann W, Maschmeyer G, Pfreundschuh M et al: Treatment of refractory acute myeloid (AML) and lymphoblastic leukemia (ALL) with high-dose cytosine arabinoside (HD-AraC) and mitox-antrone: indication of increased efficacy by sequential administration. Proc Am Soc Clin Oncol 5: 189, 1988Google Scholar
- 4.Hiddemann W, Aul C, Maschmeyer G et al: High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: Results of an age adjusted randomized comparison. Leukemia and Lymphoma 10: 133–137, 1993PubMedCrossRefGoogle Scholar
- 7.Stone RM, Mayer RJ: Treatment of the newly diagnosed adult with de novo acute myeloid leukemia. Hematol/Oncol Clin. North America: 47–64, 1993Google Scholar
- 8.Gale RP, Champlin R: How does bone marrow transplantation cure leukemia? Lancet 2: 28–30, 1987Google Scholar
- 9.Sullivan KM, Fefer A, Witherspoon R et al: Graft versus leukemia in man: Relationship of acute and chronic graft-versus-host disease to relapse of acute leukemia following allogeneic bone marrow transplantation. In: Truitt RL, Gale RP, Bortin MM eds. Cellular Immunotherapy of Cancer. New York, Alan R Liss: 391–399, 1987Google Scholar
- 10.Adler A., Chervenick PA, Whiteside TL et al: Interleukin 2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients. I. Feasability of LAK generation in adult patients with active disease and in remission. Blood 71: 709–716, 1988PubMedGoogle Scholar
- 15.Pelzer P, Garritsen HSP, Wörmann B et al: Inhibition of colony formation of leukemic blasts in acute leukemia by interleukin 2 stimulated autologous lymphocyte subsets. Blut 61: 176, 1990Google Scholar
- 16.Garritsen HSP, Segers-Nolten GMJ, Radosevic K et al: Assessment of lymphokine-activated killer activity in myeloid leukemic blasts and the myeloid cell line K562 by flow cytometry. In: Hiddemann W et al. eds. AcuteLeukemias. Pharmakokinetics and Management of Relapsed and Refractory Disease. Berlin, Springer Verlag: 581–589, 1992Google Scholar
- 17.Garritsen HSP, Kaufhold E, Pelzer P et al: Prognostic relevance and specific cytotoxic lymphocyte subpopulations in patients with acute myeloid leukemia. Onkologie 14, suppl. 2: 50, 1991Google Scholar