Recurrent Gestational Acute Myeloid Leukemia: A case report

Introduction/Background/Significance: Pregnancy induces a unique immunological state characterized by increased tolerance and controlled immune response.Acute Leukemias as usually seen in the second and third trimester and are very rarely seen in the first trimester (23%). The underlying mechanism involves reduced cytotoxic T cell activity ,increased regulatory T cells and upregulation of immune checkpoints PD-1 and weakened tumour surveillance. Hormonal and cytokine changes during pregnancy further suppress anti tumour immunity allowing malignant cells to escape detection and proliferate. The incidence of leukemia in pregnancy varies from 1 in 75,000 to 1 in 1,00,000.AML is the most common subtype .We report a rare case of pregnancy-associated FLT3-ITD-positive AML, with relapse during a second pregnancy and remission following hematopoietic stem cell transplantation.

Materials and Methods/Case Presentation/Objective: A 37 year old female at 20 weeks of gestation, came with complaints of fatigue.Complete blood count revealed a count of WBC 271,000/mm³,Hemoglobin of 6.2 g/dL, and platelets of 60,000/mm³. Bone marrow biopsy confirmed Acute Myelomonocytic Leukemia(AML) M4, with 95% cellularity, sheets of aberrant monocytes and blasts. Cytogenetics and FISH were normal.Molecular analysis showed FLT3–ITD and NPM1 mutations

She underwent daunorubicin and cytarabine (7+3) induction chemotherapy and achieved remission by day 14. The pregnancy ended in spontaneous abortion two weeks after initiating therapy. CSF analysis was negative for leukemic involvement. She completed three cycles of high-dose cytarabine consolidation with midostaurin.Allogenic stem transplant was not done at first remission due to donor unavailability.

The patient remained in remission for 2 years until she again became symptomatic and presented with similar complaints of fatigue and tiredness during early planned pregnancy (8 weeks gestation).WBC counts were 62,000 /mm³. A bone marrow biopsy showed 70% blasts with monocytic differentiation, consistent with relapsed AML. Cytogenetics and FISH remained normal and molecular analysis confirmed FLT3-ITD, NPM1 and an additional RUNX1 mutation. She received remission with venetoclax for 10 days and gilteritinib for 14 days. Cytarabine ,daunorubicin were started as well.Despite marrow clearance, her clinical course was complicated by extended spectrum beta lactamase bacteremia and septic shock, requiring ICU admission and G-CSF support.

She was discharged after a month and started on azacitidine and gilteritinib, which was held temporarily due to hepatotoxicity but re started at 80 mg daily

She underwent matched unrelated donor allogeneic hematopoietic stem cell transplant four months later following BuCy conditioning. She has been in complete remission for the past fifty two months .

Results/Description/Main Outcome Measures: She has been in complete remission for the past fifty two months.

Conclusions: This case focuses on the complex interplay between an immunocompromised state like pregnancy and AML. Early relapse during a subsequent pregnancy signifies the importance of molecular surveillance. Integration of targeted therapy and transplantation resulted in durable remission.