Neumega in myelodysplasia
The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis and persistent peripheral cytopenias. These disorders typically are difficult to manage, and the advanced age of most patients renders administration of therapy challenging.THis case as described is difficult as the patient has thromboocuyopenia and having reactions to platelt transfusions.
The survival of patients with MDS is poor, and fatal complications of MDS-associated peripheral blood cytopenias are common. Life-threatening bleeding occurs less frequently than infection in patients with MDS but still represents a major problem. The reported incidence of hemorrhagic complications in the literature ranges from 3% to 53%, and the frequency of hemorrhagic deaths is on the order of 14% to 24%. Both thrombocytopenia and platelet dysfunction may contribute to hemorrhagic complications observed in patients with MDS. Three agents are approved by the US Food and Drug Administration (FDA) for the treatment of MDS -- azacitidine, decitabine, and lenalidomide -- although none is specifically approved for the treatment of thrombocytopenia in MDS. Most of these drugs cause at least transient cytopenias if they are to be effective, making difficult the interpretation of their effect on platelet counts.
Neumega (Oprelvekin), a recombinant human interleukin (IL)-11, stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitors and induces increased platelet production through megakaryocyte maturation.[ It is approved by the FDA for the prevention of severe thrombocytopenia following myelosuppressive chemotherapy in patients with nonmyeloid malignancies at high risk for this toxicity. Two small single-arm studies have explored the use of oprelvekin in patients with bone marrow failure, including those with bone marrow failure due to MDS. In a pilot study, median platelet counts at baseline were 12 x 109/L; 38% of patients showed a platelet response. Of the 6 responders, 1 had refractory anemia (RA), 1 had RA with ringed sideroblasts (RARS), and 3 had RA with excess blasts (RAEB); the remaining responder had aplastic anemia. The duration of platelet response ranged from 12 weeks to > 30 weeks.[35] In the second study, median platelet counts were 17 x 109/L at baseline and 27% of patients responded to treatment, with either a major or minor platelet response (6 patients) or a multilineage response (3 patients).] Of the responders, 4 had RAEB, 1 had RARS, and the remainder had chronic myelomonocytic leukemia or aplastic anemia. The duration of response ranged from 1.4 to ≥ 34.5 months. Most of the toxicities observed in these trials were mild (peripheral edema, conjunctival infection, fatigue, arthralgia, and myalgia). However, 1 patient in the second study had a transient ischemic attack after completing treatment and 1 patient developed atrial fibrillation/supraventricular tachycardia. Other cardiovascular events, such as arrhythmias and pulmonary edema, have also been observed in oprelvekin-treated patients. Oprelvekin also has been associated with allergic and hypersensitivity reactions, including anaphylaxis, and serious fluid retention, which has been fatal in some patients. Papilledema has also been reported and is more common in children; therefore, oprelvekin is not indicated for use in the pediatric population. It is also not indicated for use following myeloablative chemotherapy; a clinical study showed a significant increase in side effects in this population compared with placebo. The evidence for activiry of Neumaega in MDS is preliminary.
Tsimberidou AM, Giles FJ, Khouri I, et al. Low-dose interleukin-11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center experience. Ann Oncol. 2005;16:139-145. Abstract
Kurzrock R, Cortes J, Thomas DA, Jeha S, Pilat S, Talpaz M. Pilot study of low-dose interleukin-11 in patients with bone marrow failure. J Clin Oncol. 2001;19:4165-4172
