Pb2248: bone marrow necrosis: rare presentation of chronic myeloid neoplasms systemic review and case report

Topic: 16. Myeloproliferative neoplasms - Clinical Background: The prevalence of bone marrow necrosis (BMN) with hematological malignancy (HM) is 0.3% to 2.2%. Very rarely, BMN has been reported with chronic myeloid neoplasms (CMN). BMN is defined as necrosis of myeloid tissue and medullary stroma in large areas of the hematopoietic bone marrow. The presence of BMN has also been associated with poor survival outcomes in HM. Aims: To describe the outcomes of CMN associated with BMN Methods: A literature search was conducted with MEDLINE. PubMED, and Google Scholar, using search terms bone marrow necrosis, myeloproliferative neoplasm, myeloid neoplasm, chronic myeloid neoplasms, polycythemia vera, essential thrombocythemia, and myelofibrosis. The search was limited to articles (ART) in English. Resulting in 21 ART. ART reporting about pediatric population and solely about acute leukemia were removed. A total of 7 publications comprising total of 8 cases spanning 29 years (1994-2023) were reviewed. Results: Our case is a 64M developed left hip pain with Hb: 94g/L, Plt: 30 x109/L, WBC: 6.1x109/L and peripheral blast (PB) 2%. After 3 non-diagnostic BmBx, there was suspicion for myeloproliferative neoplasm unclassifiable. Referral to Princess Margaret for diagnostic clarification. Repeat BmBx showed necrosis, granulopoiesis with left shift, with reticulin fibrosis grade 2, with blast >10%. Flow showed 14% of cells positive for CD13, CD33, CD34, CD45, CD71, CD105, CD117, CyMPO, HLA-DR and negative: sCD3, CyCD3, CD10, CD11b, CD14, CD16, CD19, CD35, CD36, CD56, CD64, cyCD79a, CD300e, TdT. Next Generation Sequencing (NGS): ASXL1, DNMT3A, NPM1, TET2 with normal cytogenetics. Myeloid neoplasm with fibrosis accelerated phase. Patient was treated with induction chemotherapy and achieved remission. Including our case, we found a total of 9 cases of BMN with a diagnosis of CMN (See table 1 for details). Patients experience bone pain in 66.7% of the cases (N=6/9), 55.6% (N=5/9) experience 1 or more constitutional symptoms of either fevers, drenching night sweats and/or unintentional weight loss. All (N=9/9, 100%) of the patients in this presentation experienced anemia and/or thrombocytopenia. One patient developed pancytopenia during hospitalization, repeat marrow BMN diagnosed concurrently with disease transformation to AML secondary to polycythemia vera. Three cases were lost to follow-up. Thirty-three percent (N=3/9) early mortality was seen, and one patient although time of death not provided, was transferred to a hospice. One patient with myeloid neoplasm and NPM1 and TET2 mutation responded well with induction and consolidation chemotherapy with resolution of BMN on repeat marrow. Our patient had undergone FLAG-IDA induction and achieved complete remission. Summary/Conclusion: BMN in CMN is a rare entity, patients often present with cytopenia. Bone pain and constitutional symptoms are the next most common clinical manifestations. BMN in this report also seems to be associated with poor prognostic outcomes. However, BMN poses diagnostic challenges, as the necrotized trephine provides little to no cellular component for diagnostic analysis; in such situations, NGS and cytogenetics have important diagnostic implications, and may change the diagnosis from CMN to an acute leukemia, utilizing the ELN 2022 guidelines, which in turn has implications on treatment. In our case and Saito et al, in both cases although blast was below 10%, but the utilization of intensive chemotherapy resulted in positive patient outcomes.Keywords: Myelofibrosis, Bone Marrow Fibrosis, Myeloid malignancies, Osteonecrosis