Is Thalidomide the Sole Treatment of Primary Myelofibrosis? Report of a Case with Complete Reversal of Bone Marrow Fibrosis and Splenomegaly.

Primary myelofibrosis (MF) is a chronic progressive disorder incurable except for allo-transplantation in young patients. Thalidomide which down-regulates cytokine release involved in fibrosis (VEGF, TGF-beta, beta-FGF, PDGF) and angiogenesis has been used with variable responses in the treatment of MF. We report a patient who achieved a complete response of MF after being treated with low doses thalidomide.

An 82-year-old patient, with no other medical problems, was followed since 1993 because of erythrocytosis and mild splenomegaly, his bone marrow biopsy revealed tree-lineage hyperplasia and moderate fibrosis. The patient was initially treated with phlebotomy when needed, and afterwards by a low dose of hydroxyurea. Five years later, when anemia developed (Hb<10 g/dl) together with prominent splenomegaly (18 cm) and aggravation of bone marrow fibrosis, combination treatment with androgen, vitamin B complex and folic acid was started. Since 2003 the patient became transfusion dependent (2 packed red cells every 3 weeks). He had a huge splenomegaly (up to the pubis), Hb 8.3 g/dl, WBC 4×10⁹/l with occasionally blasts, platelet count 75×10⁹/l, and LDH 1220 U. Bone marrow biopsy revealed severe reticulin and collagen fibrosis with no hematopoiesis. In view of the progressive painful splenomegaly and deep pancytopenia, splenectomy was advised which was refused by the patient.

Therefore alternative treatment with thalidomide was considered and started at a dose of 50 mg/day together with 5 mg/day prednisone in March, 2004. B-complex and folic acid were continued. Four months later, the blood transfusion requirement decreased, and gradually was abolished. The spleen size started to be smaller and became impalpable. Currently after 30 months of treatment blood count showed Hb 12.0 g/dl, WBC 2.6×10^9//l, Plt 140×10⁹/l. The repeated bone biopsy showed a dramatic change with complete normalization of hematopoiesis and total resolution of collagen. The blood film doesn’t disclose any tear drops.

Thalidomide monotherapy in moderate and high doses (200–800 mg/day) produces a 20–50% response rate in MF-associated anemia and thrombocytopenia, has mild impact on splenomegaly, but is poorly tolerated. Most patients are withdrawn from treatment because of adverse effects in first three months. Mesa et al (Blood, 2003) improved tolerability and efficacy of therapy using thalidomide in low dose 50 mg/day along with a three months oral prednisone. An objective clinical response was demonstrated in 62% patients; however, complete reversal of fibrosis has never been mentioned before.

In conclusion, we report a patient with a very advanced MF who showed complete hematological response to low dose thalidomide with complete reversal of bone marrow fibrosis and splenomegaly. We suggest that this exceptional response might be due to the long continuous tolerable low dose treatment (30 months) and a combination with prednisone, B-complex vitamins and folic acid.