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 10 mug/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 thrombocytopenia following stem cell transplantation or chemotherapy, 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 creatinine 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.