The Efficacy Of RhIL-11 In The Management Of Postremission Consolidation Chemotherapy-Induced Thrombocytopenia In Acute Myeloid Leukemia

Retrospective analyses of cooperative group studies show that increasing the intensity of postremission chemotherapy is beneficial in younger adults with acute myeloid leukemia. But it is frequently accompanied by anemia, neutropenia, thrombocytopenia, or some combination of these conditions. These complications can potentially increase the morbidity or even mortality .While chemotherapy-related anemia and neutropenia are often adequately managed by use of currently available hematopoietic growth factors (e.g.G-CSF and EPO), thrombocytopenia remains a significant contributor to morbidity and mortality in patients with this disease. In addition, the presence of significant thrombocytopenia could -possibly limit the benefits of modern therapy for potentially curable malignancies by preventing appropriate administration of drugs at the optimal doses and schedule. Nowadays platelet transfusions remain the "gold-standard" for the acute management of severe thrombocytopenia, there are many resource issues and possible complications associated with their use. Consequently, the hematologist is engaged in a search for alternative therapeutic interventions to raise platelet counts. Recombinant human interleukin-11 (rhIL-11) was the first commercially available thrombocytopoietic cytokine. It is licensed for the prevention of severe thrombocytopenia and the reductionof the need for platelet transfusion following myelosuppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia. So far rhIL-11 was studied in only a few clinical trials on acute myeloid leukemia.Objective: To evaluate the efficacy and safety of rhIL-11 in the management of the postremission consolidation chemotherapy-induced thrombocytopenia in acute myeloid leukemia.Methods: Thirty eight acute myeloid leukemia patients who achieved complete remission or partial remission(myeloblasts or myeloblasts + promylocytes<5% was required) after their first induction chemotherapies were enrolled into auto-controlled clinical trial, and each one of them received 2 cycles of the same consolidation chemotherapies in three months. Patients only received consolidation chemotherapy in the control cycle, and in the treatment cycle rhIL-11 was given when platelet count ^ 50 X 109/L after consolidation chemotherapy, at 25 u g/kg (1.5mg),subcutenously,daily ,at least 7 days until the platelet count was higher than 50 X109/L.Result: Thirty two of 38 patients were eligible for assessment of efficacy. The minimum platelet count due to consolidation chemotherapy in the two cycles had statistic significance(P=0.007).In the treatment cycle, the duration of the platelet count under 20X 109/L was shorter than in the control cycle (P=0.001) ,and more patients received platelet transfusion in control cycle( 16/32 )than in treatment cycle( 8 / 32 ) (P=0.039). In these two cycles there was no statistic significance in the ratio of blast cells in bone marrow before and after consolidation chemotherapy (P>0.05),while the proportion of mature megakaryocytes in bone marrow after consolidation chemotherapy had statistic significance (P=0.02). Thirty six of 38 patients were eligible for assessment of safety. Major adverse events associated with rhIL-11 when it was administered at a dose of 25 u g/kg per day were edema, arthralgia/myalgia, fatigue and anemia, and one patient experienced symptomatic atrial fibrillation which required drug cardioversion. Most adverse events were mild, tolerable and reversible with rhIL-11 discontinuation.Conclusion: This study shows that when rhIL-11 is administered at a dose of 25 Ug/kg per day it can accelerate the platelet recovery and reduces the need for platelet transfusion after postremission consolidation chemotherapy in acute myeloid leukemia, and it shows rhIL-11 plays an important role in the production,differention and maturation of megkaryocytes. When rhIL-11 is administered at a dose of 25 u g/kg per day most adverse events are mild, tolerable and reversible with rhIL-11 discontinuation.