Journal of Clinical and Diagnostic Research. 2022 Aug, Vol-16(8): ED10-ED12 10 10 DOI: 10.7860/JCDR/2022/56765.16749 Case Report Pathology Section Unusual Presentation of Aplastic Anaemia: Evolving into Myelodysplastic Syndrome with Excess Blasts 1 and Type III Paroxysmal Nocturnal Haemoglobinuria Clone CASE REPORT Twenty six years old male patient, known case of Aplastic anaemia (AA), diagnosed at All India Institute of Medical Sciences (AIIMS), New Delhi in April 2014, presented with weakness and fatigability in September 2021. In 2014, Patient had pancytopenia with hemoglobin of 6.1 g/dL, Total Leucocyte Count (TLC) of 3000/mm 3 and platelet count of 70,000/mm 3 . Bone Marrow Biopsy (BMB) showed a patchy cellularity of 15-20% with increased lymphocytes and plasma cells. Patient received Immunosuppressive Therapy (IST) with Cyclosporine and 20-25 units Packed Red Blood Cells (RBCs). He had an uneventful disease progression from year 2016-2019. In January 2020, patient started having complaints of fatigability and weakness. He underwent Bone Marrow Aspirate (BMA) and biopsy in September 2020 which revealed patchy cellularity of 15-20% with increased lymphocytes and plasma cells. BMA revealed 2% blasts with myeloid to elytroid (M:E) ratio of 1:3 and increased iron deposition (Grade 4). He eventually came to our hospital for allogeneic HSCT with a clinical diagnosis of AA in September 2021. He had a fully matched donor with 6/6 HLA matching from his sister. The authors advised a fresh BMA and BMB. His hemoglobin at this point was 3.7 g/ dL, TLC was 2500/mm 3 and platelet count 13,000/mm 3 . BMA was adequate with 50% cellularity and 7% blasts and M:E ratio of 2:1 [Table/Fig-1]. Dysmegakaryopoiesis was noted in the form of micro megakaryocytes and hypolobated megakaryocytes. BMB [Table/ Fig-2] demonstrated similar findings with presence of blasts in the para trabecular spaces, which showed membranous positivity for CD34 and membranous and cytoplasmic positivity for CD117 [Table/Fig-3,4]. Final impression was AA converted to MDS with excess blasts-1 (MDS-EB-1), World Health Organisation (WHO) 2016 Classification [1]. The authors also got Fluorescein-labeled proaerolysin (FLAER) test for detection of Paroxysmal Nocturnal Haemoglobinuria (PNH) clone and immunophenotyping by flow cytometer along with cytogenetics study for MDS. FLAER was positive for type III PNH SHILPI MORE 1 , SAROJ RAJPUT 2 , GEETIKA SHARMA 3 , NIMISHA SHARMA 4 , TATHAGATA CHATTERJEE 5 Keywords: Haematopoietic stem cell transplant, Human leucocyte antigen, Immunosuppressive therapy, Pancytopenia ABSTRACT Aplastic Anaemia (AA) is an immune mediated, primary haematopoietic disorder characterized by pancytopenia with significant morbidity and mortality. Allogeneic Haematopoietic Stem Cell Transplant (HSCT) is the treatment of choice in younger patients whenever Human Leucocyte Antigen (HLA) matched donor is available. For older patients and those in whom matched donor is not available, immunosuppressive therapy is the frontline treatment. With the long survivals of AA patients, clonal evolution into Myelodysplastic Syndrome (MDS) and clinically evident Paraoxysmal Nocturnal Haemoglobinuria (PNH) is frequently seen over a period of 5-10 years. The prognosis and overall survival of post AA, MDS is poor and the only treatment of choice is Allogeneic HSCT. The overall survival of post AA, MDS is however comparable to de novo MDS post-transplant. The authors hereby discuss a case of 26 years old male patient, known case of AA who evolved into MDS with Excess Blasts 1 (MDS-EB-1) and type III PNH clone over a period of six years. [Table/Fig-1]: Bone Marrow Aspirate (BMA) smears (400X) (Leishman Giemsa) were cellular showing 50% cellularity with normoblastic erythroid maturation, myeloid series showing all stages of maturation with 7% blasts (highlighted by arrows) and M:E ratio of 2:1 clone. Flow cytometer revealed the blasts to be positive for Cluster of Differentiation (CD)45, HLADR, CD13, CD33, CD14, CD64, CD11b with aberrant expression of CD7 and cytoplasmic CD3 (cCD3). Cytogenetics by Fluorescence in-situ Hybridization (FISH) showed positivity for deletion (del) 7q; del 5q, del 20q and trisomy 8 were found to be negative. Overall impression was AA converted into MDS-EB-1 with del 7q and type III PNH clone. Patient was taken up for Allogeneic HSCT with reduced-toxicity conditioning regimen with Treosulfan, Fludarabine and Grafalon (ATG). He was transfused with stem cell harvest on Day 6 with the CD34 dose being 6 million/Kg body weight. Daily hologram and