Abstract
Introduction: Erythroblastic sarcoma (ES) is a rare form of myeloid sarcoma(MS). We report an unusual case of ES transforming from chronic myeloid Leukaemia (CML).
Case Summary: A 46-year-old female was referred to our institution in November 2023 with a five-week history of cervical and axillary lymphadenopathy and fatigue. white blood cell 95.3 × 10⁹/L, Haemoglobin 111 g/L, and platelet count 253 × 10⁹/L. Bone marrow biopsy showed no significant dysplasia or excess blasts. Cytogenetics/FISH: t(9;22) positive. The diagnosis of CML in chronic phase was confirmed. Repeated lymph node biopsies showed a nonspecific inflammatory infiltrate with no evidence of chloroma or lymphoma.
She was started on Dasatinib 100 mg daily, but the dose was reduced due to intolerance. Her lymphadenopathy improved. Serial molecular monitoring showed an initial favourable response with BCR-ABL1 IS% decreasing to 2.19% at three months and 0.10% at ten months. However, at thirteen months, the patient experienced molecular relapse with BCR-ABL1 IS% of 9.54%. At the same time, the patient developed progressive left breast enlargement, axillary and supraclavicular lymphadenopathy, acute respiratory symptoms and increased left neck pain & swelling, and oedema of the left upper limb and breast. Dasatinib was held due to concerns of drug-related pleural effusion and disease progression. Cross-sectional imaging revealed a moderate left-sided pleural effusion, widespread disease dissemination, including sclerotic bone lesions, mediastinal and axillary lymphadenopathy, a 7.1 × 5.8 cm left cervical nodal mass, causing significant left internal jugular vein compression. Repeat bone marrow biopsy showed: 90% cellularity; 2% myeloblasts; PB: 16% basophils consistent with accelerated phase CML. Cytogenetics: Complex karyotype with t(9;22), +19, +8, inv(7), extra Ph chromosome, FISH: Positive for BCR-ABL with extra Ph; Negative for chromosome 7/p53 abnormalities, ABL1 Kinase Domain Mutation Testing: No mutations detected. Pleural Fluid Flow Cytometry: 48% immature erythroid precursors (erythroblastic sarcoma phenotype); CD117+, CD71+, CD36+, CD38+, CD7+, CD123+, CD33+.Left neck core biopsy this time revealed sheets of leukemic erythroid blasts. Breast biopsy showed no evidence of malignancy.
Ponatinib was started at a dose of 30 mg daily, subsequently reduced to 15 mg due to severe hypertension despite triple anti-hypertensive medications and Induction chemotherapy DA 7+3 regimen (cytarabine and anthracycline). Imaging revealed bilateral pleural effusions. A right-sided chest drain was inserted, which drained chylous fluid, confirming chylothorax. Post-induction therapy imaging showed marked regression of all previous lesions, no active bone lesions and resolving pleural effusions. Bone marrow biopsy: Normocellular (60%) with trilineage haematopoiesis; no evidence of leukaemia and pleural Fluid Cytology negative for malignant cells. BCR-ABL1 PCR: Negative (P210 and P190). She received three cycles of high-dose cytarabine and ponatinib. After extensive discussion, our patient declined consolidation with an Allogeneic stem cell transplant (AlloSCT). She continues to receive ponatinib with plans to add Azacitidine.
Discussion: Our patient case is unique as she had extra medullary manifestations at the time of the diagnosis of CML; however, repeated tissue biopsies failed to show any abnormal cells. Those changes responded well to initial CML treatment but returned in aggressive forms once the disease transformed to erythroblastic sarcoma. She developed extensive ES involving multiple organs with evolving molecular changes and disease acceleration in the bone marrow associated with the ES transformation. She responded well to intensive chemotherapy and Ponatinib. Currently, there is no data to support further treatment beyond AlloSCT.
Conclusions: Myeloid Sarcoma is a rare form of myeloid malignancies, which is usually composed of myeloblasts, Monoblasts or megakaryoblasts. Erythroblastic sarcoma is a rare form of MS which is associated with a poor prognosis. ES Transformation from CML is extremely rare, with only a few cases reported in the literature. Given the limited number of published cases, Diagnosis and treatment can be challenging. Currently, treatment follows protocols for acute myeloid leukaemia. Large case series are required to establish the best management plans.
