Tsimberidou, A.M., Giles, F.J., Khouri, I., Bueso-Ramos, C., Pilat, S., Thomas, D.A., . . . Kurzrock, R. (2005). Low-dose interleukin-11 in patients with bone marrow failure: Update of the MD Anderson Cancer Center experience. Annals of Oncology, 16, 139–145.

Interleukin-11 (IL-11) 10 mcg/kg subcutaneous was given daily for two weeks followed by a two-week rest period for two induction courses. Patients with grade 0–1 toxicity during a course could have a 5 mcg/kg/day dose increase in subsequent courses. If grade 3 toxicity was reached, the dose was decreased by 50%. If grade 4 toxicity was reached, therapy was stopped. Responders could receive maintenance therapy of the same daily dose used in induction (10 mcg/kg) given on alternate days or daily. For grade 3 or lower toxicity, the dose could increase by 5 mcg/kg. Therapy continued as long as there was hematologic improvement without grade 3 or 4 toxicity.

• N = 33
• AGE: 5–85 years
• MALES: 25, FEMALES: 8             
• OTHER KEY SAMPLE CHARACTERISTICS: Bone marrow failure because of myelodysplastic syndrome (MDS), graft failure, aplastic anemia (AA), or chemotherapy. Platelet count 20 or less, or a platelet of less than 50 with an absolute neutrophil count less than 1 or hemoglobin less than 10 g/dl. No chemotherapy for more than two months and no disease progression. Patients with AA, no anti-thymocyte globulin for three months prior. Bone marrow biopsy and aspirate prior to treatment, at time of response, and post-therapy for those who lost their response.

• Assess toxicity, safety, response, and efficacy.

Twenty-seven percent (nine patients—eight patients at 10 mcg dose, one patient at 15 mcg dose) responded. Patients were 56–78 years of age. The median time to response was 0.9 months (higher response rate with patients older than 50 years [P = 0.008], MDS versus AA [P=0.025], and creatinine greater than 1 mg/dl [P = 0.0004]). Lower baseline platelet counts (less than five) took months to respond. The median response duration was three months. Among responders, the median maximum post-treatment platelet count was 137. Five patients showed multilineage response; three were treated with IL-11 alone, and two were treated with IL-11 plus erythropoietin and granulocyte colony-stimulating factor. The most common side effects for grade 1–2 were lower extremity edema, conjunctiva infection, and fatigue. Grade 3 toxicities were arrhythmia and transient ischemic attack. Ten patients had no side effects. Patients on maintenance therapy received a range of 35–70 mg/kg weekly cumulative.
 

• What was the alternate dosing schedule?
• Small subgroup of patients
• Wide variety of maintenance dosing
• No control
• Age range of participants