Myelofibrosis and following chronic myeloid leukemia: imatinib and ruxolitinib treatment in two cases

Myelofibrosis (MF) is a stem cell derived disorder characterised by bone marrow fibrosis, extramedullary hematopoiesis, anemia, splenomegaly, constitutional symptoms, leukemic progression and shortened survival. It can be primary or secondary to evolution from polycythemia vera (PV) or essential thrombocythemia. JAK2 V617F mutation is present in almost 50% of cases and recently Jak-2 inhibitors have been successfully used in some of these patients. Very few MF cases are reported to develop chronic myeloid leukemia (CML) during the follow-up. Herein we report two cases of post-PV MF that developed CML 7 years after their initial presentation. Case 1: a 48 year old man was diagnosed with PV in 1992; he was treated with hydrossiurea, antiplatelet therapy and phlebotomy. Thirteen years later, after increasing of splenomegaly and a decrease of haemoglobin level, a new bone marrow evaluation was performed and according to WHO criteria, post-PV MF Jak2 positive was diagnosed. He continued cytoreductive therapy at a low dose. On December 2011 t(9;22)(q34;q11.2) [2/30] was detected on bone marrow, suggesting the presence of a Philadelphia positive CML clone. PCR analysis showed a BCR-ABL transcript (b2a2). Consequently, cytoreductive therapy was stopped and imatinib started at a daily dose of 400 mg. A complete cytogenetic and major molecular response were achieved after 10 months, but this treatment had no effect on MF (increase splenomegaly, constitutional symptoms); therefore we added ruxolitinib at 15mg BID. Case 2: a 49-year old man was diagnosed with PV in 2000, after a recovery for TIA. He started an anticoagulant and a cytoreductive therapy with hydrossiurea. Five years later after increasing of splenomegaly and decrease of haemoglobin level, evolution to MF was observed. On March 2012 bone marrow evaluation confirmed a myelofibrosis (MF-3), but at cytogenetic evaluation, t(9;22)(q34;q11.2) was detected. PCR analysis on peripheral blood showed the BCR-ABL transcript (b3a2). He stopped the previous therapy and started imatinib at a daily dose of 400 mg. Six months later, a complete cytogenetic response was achieved. After observing an increase of splenomegaly and Jak-2 allele burden and the presence of constitutional symptoms, ruxolitinib at 15mg BID was started. Conclusion: these rare cases of MF and following CML, obtained improving clinical conditions and reduction of splenomegaly with imatinib and ruxolitinib unusual association.