Low-dose interleukin-11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center experience

Background: Recombinant interleukin (IL)-11 is a thrombopoietic growth factor. The purpose of this study was to assess the toxicity, safety and efficacy of low-dose recombinant IL-11 in patients with bone marrow failure (BMF). Patients and methods: Patients with BMF due to myelodysplastic syndromes (MDS), graft failure. chemotherapy or aplastic anemia (AA) were treated. Patients were required to have a platelet count of <20 x 10(9)/l, or a platelet count of <50 x 10(9)/l with an absolute neutrophil count <1 x 10(9)/l or a hemoglobin value <10 g/dl. Treatment consisted of daily IL-11 at a dose of 10mug/kg subcutaneously followed by a 2-week rest period. Two induction courses were given. Responders could receive maintenance therapy. Results: Thirty-three patients (MDS, n = 14; AA, n = 16; prolonged thrombocytopena following stem cell transplantation or chemtherapy, n = 3) were evaluable. Their median age was 58 years (range 5-85). Three patients (9%) had poor risk cytogenetics. Nine patients (27%) responded to IL-11 (six MDS, three AA). Of these, three patients treated with IL-11 alone (n = 1) or IL-11 together with other growth factors (n=2) showed multilineage recovery. The median time to response was 0.9 months (range 0.3-11). Factors associated with higher response rates in univariate analysis were age >50 years (P = 0.008), diagnosis of MDS versus AA (P = 0.025) and creatine level >1 mg/dl (P = 0.0004). The median response duration was 3 months (range 1.4-34.5+). Amongst responders, the median increment in platelet count was 111 x 10(9)/l (range 43-165). The most common side-effects were grade 1-2 lower extremity edema, conjunctival injections and fatigue. Grade 3 toxicities included arrhythmia (n = 1) and transient ischemic attack (n = 1). Ten patients (30%) had no side-effects. Conclusions: Low-dose IL-11 has activity in patients with BMF and is generally well tolerated.