A recent letter by Tefferi and Eliott1 reported the development of a myeloproliferative reaction and thrombocytosis after thalidomide administration in myelofibrosis with myeloid metaplasia. Thalidomide is being used currently with promising results, in the treatment of refractory multiple myeloma,2other plasmacytic dyscrasias,3 and myelofibrosis.4 The reported results of the ongoing therapeutic trials with thalidomide are preliminary. Therefore, the side effects of this drug are not entirely known.
In this letter we present a patient with a monoclonal gammopathy of undetermined significance secreting IgM (IgM-MGUS) who underwent treatment with thalidomide followed by a monoclonal antibody against the CD20 antigen (anti-CD20, mabthera) and developed thrombocytosis along with features of bone marrow dysplasia with excess of blasts.
During a routine examination, an asymptomatic 72-year-old man was found to have a mild anemia (Hb concentration of 12.5 g/dL) with white blood cell (WBC) count of 7.2 × 109/L, normal differential, and platelet (PLT) count of 232 × 109/L. No evidence of blood loss or nutritional deficiency was found (normal iron, ferritin, folate, and vitamin B12levels). Bone-marrow smear and trephine biopsy were normal. Biochemistry and immunology tests revealed only a small (480 mg/dL) IgMκ monoclonal compound present in the serum without proteinuria. Computed tomography (CT) scans of the chest and abdomen did not reveal any abnormality. He was then diagnosed as having an IgM-MGUS, and in the context of a therapeutic trial conducted in another hospital, he was administered 200 mg thalidomide daily, but this regimen was stopped after 20 days because of constipation, dizziness, and edema of the lower extremities. After thalidomide, his Hb concentration was 11.3 g/dL and his WBC count, 4 × 109/L, with normal differential and PLT count of 497 × 109/L. Treatment continued as scheduled by their protocol with 4 courses of 375mg/m2 anti-CD20 weekly. One month after completion of treatment with the anti-CD20 and 2 months after thalidomide, he had Hb concentration of 8.6 g/dL, WBC count of 3.6 × 109/L, PLT count of 650 × 109/L, and IgM count of 1180 mg/dL. Two months later, he presented to our department with an Hb concetration of 8.1 g/dL, WBC count of 2.4 × 109/L (neutrophils 60%, lymphocytes 31%, monocytes 9%), and PLT count of 1000 × 109/L. Bone marrow smear and trephine biopsy revealed an hyperplastic marrow with marked dysplasia of the erythrocyte progenitors, highly increased number of markedly dysplastic megakaryocytes, left shifted myeloid series with 20% blasts, and 30% lymphocytic infiltration by small B-lymphoid cells and lymphoplasmacytes (cIgκ). Immunophenotype of the bone marrow, by flow cytometry, confirmed the presence of an immature blast, cell population that was CD13+, CD34+, and CD38+, and a lymphocytic component that was CD20+ and CD5− with κ light-chain restriction; karyotype was normal. The patient is currently being given hydroxyurea with a PLT count reduction to 740 × 109/L after 2 weeks' administration.
It seems that the administration of thalidomide and the anti-CD20 monoclonal antibody was ineffective in controlling the IgM-MGUS problem that subsequently evolved into Waldenstrom macroglobulinemia; on the other hand, it caused a myeloproliferative reaction leading to a myeloproliferative disorder not precisely classifiable, which, however, is currently the major hematologic problem of this patient. This case is another example of myeloproliferative reaction with marked thrombocytosis after thalidomide administration as reported by Tefferi and Eliott.1 These observations indicate that, until thalidomide's mode of action and its complications are better known, this drug should be used with great caution.
