PB2241 AN UNCOMMON CASE OF SECONDARY MYELOFIBROSIS RELAPSING AS MYELOID SARCOMA

Abstract

Background: Despite the advent of many novel agents, allogeneic hematopoietic stem cell transplant (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Long-term mortality after transplantation results from relapse of MF, followed by GvHD, infections and secondary cancers. The most common secondary cancers are solid neoplasms, 70% of which are breast cancer, followed by second leukemias and myelodysplastic syndromes. Myeloid sarcoma (MS) secondary to a MF has been described as a rare entity. Aims: We report a case of a patient with MS following MF treated with alloHSCT with multiple bone lesions in order to provide a better knowledge about this disease. Methods: A 54-year-old lady with a past medical history of haemochromatosis was diagnosed with JAK2 mutated essential thrombocythemia in 2004. After initial treatment with anegralide, she received acetylsalicicylic acid and hydroxycarbamide, which controlled her disease until 2014. She then developed night sweats and arthralgia followed by progressive anaemia in 2015. A bone marrow biopsy performed in 2016 showed a transformation to MF. Consequently, the patient stopped taking hydroxycarbamide and was treated with ruxolitinib and transfusional supportive therapy. Ruxolitinib did not improve her condition, but it increased the severity of viral upper respiratory tract infections as well as her night sweats and joint pains. Due to this deterioration, the patient underwent a 11/12 HLA matched unrelated alloHSCT with a conditioning regimen of fludarabine, busulfan and antithymocyte globulin in June 2017. After transplant she was in morphological remission with full donor chimerism. In the post-transplant period she developed acute and then chronic GvHD involving skin, mouth and liver that was well controlled by immunosuppressive therapy with ciclosporin, mycophenolate mofetil and steroids. Results: In September 2018 she presented with a spontaneous fracture of her left fibular. An X-Ray showed multiple lytic lesions in her left fibula which progressed over two months. An open biopsy of right tibia and fibula was performed, and the histopathological examination revealed the presence of a myeloid sarcoma with mainly megakaryocytic differentiation. Immunohistochemistry showed that the majority of cells expressed CD42b (mature megakaryocytes), CD61 (mononuclear cells) and 10-20% of the cellular population expressed CD34, while clusters of cells expressed CD117, CD20, CD3, myeloperoxidase and Ret40f. Staining for AE1/3, desmin and S100 was negative and the Ki67 proliferation fraction was moderately high (up to 60%) in the lesion cells. Furthermore, a FDG-PET/CT detected widespread multiple lytic bone lesions with cortical erosion and destruction with occasional soft tissue component. The largest and most FDG avid lesion was at the right sacrum measuring 34 mm in diameter (SUV max 6.4). The patient underwent induction chemotherapy with the FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF), followed by a donor lymphocyte infusion (1 × 106 CD3+/Kg) as consolidation treatment. The FDG-PET/CT performed after two months showed an improvement of most lesions (the right sacral lesion had a SUV max of 4.0, previous 6.4), confirming a partial remission. The patient is now very well, with no symptoms of MF and no signs of GvHD. Summary/Conclusion: MS following MF is a very uncommon event and its prognosis is not yet well understood. Therefore, each case description is fundamental to enhance the understanding of this singular malignancy.