Additional Causes of Bone Marrow Failure

Aplastic anemia—peripheral blood findings

Pancytopenia with low WBC, low ANC, anemia, thrombocytopenia, and very low reticulocyte count

Aplastic anemia—bone marrow findings

Hypocellular marrow with markedly decreased hematopoietic cells (“empty marrow”), replaced by fat

Pathophysiology of aplastic anemia

Idiopathic immune-mediated destruction of pluripotent stem cells

Causes of aplastic anemia

Congenital (Fanconi), radiation, chemotherapy, medications, viral infections (non-A/B/C hepatitis, HIV, EBV), autoimmune disease (SLE), GVHD

Treatment of aplastic anemia

Remove offending agents, supportive care, immunosuppression (steroids, cyclosporine), allogeneic stem cell transplant

Paroxysmal Nocturnal Hemoglobinuria (PNH)—pathophysiology

PIGA mutation → loss of GPI anchors → absence of CD55/CD59 shield → complement-mediated intravascular hemolysis

Paroxysmal Nocturnal Hemoglobinuria (PNH)—initial hematologic abnormality

Intravascular hemolytic anemia with elevated LDH, low haptoglobin, hemoglobinemia, hemoglobinuria

Paroxysmal Nocturnal Hemoglobinuria (PNH)—late hematologic abnormality

Pancytopenia due to stem cell involvement and progression toward aplastic anemia

Paroxysmal Nocturnal Hemoglobinuria (PNH)—major causes of death

Infection, hemorrhage, thrombosis, renal failure, progression to MDS/AML

Paroxysmal Nocturnal Hemoglobinuria (PNH)—diagnostic test

Flow cytometry showing absence of CD55 and CD59 on RBCs/WBCs

Paroxysmal Nocturnal Hemoglobinuria (PNH)—treatment

Eculizumab (anti-C5 monoclonal antibody) to block terminal complement activation

Myelodysplastic Syndromes (MDS)—peripheral blood findings

Cytopenias (anemia, neutropenia, thrombocytopenia) with dysplastic cells bc it is a disorder of ineffective hematopoesis

Myelodysplastic Syndromes (MDS)—clinical presentation

Fatigue, infections, bleeding

Myelodysplastic Syndromes (MDS)—two diagnostic criterion

Hypercellular marrow + cytopenias + dysplasia with normal blast count (<5%)

OR

Hypercellular marrow + cytopenias + increased blasts (6–19%) without meeting AML threshold

Blast cutoff distinguishing Myelodysplastic Syndromes (MDS) from AML

≥20% blasts = AML

MDS—treatment

Supportive care, transfusions, growth factors (EPO, G-CSF), iron chelation, gentle chemotherapy, monitor for AML transformation

MDS—5q- syndrome

Isolated del(5q), more benign course, responsive to lenalidomide