Definition (Hematology Am Soc Hematol Educ Program 2009:329)
• Pancytopenia: Anemia, thrombocytopenia, leukopenia
Diagnostic Evaluation: Exam for signs of anemia &/or thrombocytopenia
• Exam for dysmorphic features (eval for inherited etiologies)
• Labs: CBC, serum aminotransferases, viral serologies (HIV, CMV, EBV, hepatitis, parvo, HSV), folate, B12, Hgb F, BM aspirate and biopsy, marrow cytogenetics, drug screen
• Specific labs: Diepoxybutane for Fanconi anemia; CD 55/59 screen for paroxysmal nocturnal hemoglobinuria, HLA tissue typing
Aplastic Anemia (Lancet 2005;365:1647; Ann Intern Med 2002;136:534)
• Pancytopenia (2 of the following—ANC < 500/μL, retics < 1%, platelets < 20,000), and hypocellular bone marrow; 2/2 injury or loss of hematopoietic stem cells
• Incidence triphasic, w/ 1 peak in childhood (2–5 yr; 2/2 inherited causes), and 2 peaks in adulthood, 20–25 yr and majority pts presenting beyond 55–60 yo
• Complications: Infxns (2/2 neutropenia), bleeding (decr Plts), and findings of anemia, cancer susceptibility (Br J Haematol 2010;150:179)
• Acquired: Idiopathic, chemo/XRT, drugs (gold, NSAIDs, AEDs, sulfa), chemicals (benzene), viral (parvo B19, Non-A, B, C hepatitis, HIV, EBV), immune (SLE), misc (pregnancy, thymoma, paroxysmal nocturnal hemoglobinuria)
• Paroxysmal nocturnal hemoglobinuria: Rare in children, intravascular hemolysis, nocturnal hemoglobinuria, thrombotic events, serious infections, bone marrow failure, a/w GPI-anchor protein deficiency (Br J Haematol 2005;128:571)
• Inherited
• Fanconi anemia: Café-au-lait spots, abn of thumbs, hypogonadism, microcephaly
• Dyskeratosis congenita: Nail dystrophy, early hair graying or loss, leukoplakia, hyperpigmented rash, dysmorphic teeth, enamel hypoplasia, restrictive pulm dz, or pulm vasc dz
• Shwachman–Diamond syndrome: Exocrine pancreatic insufficiency, short stature, skeletal anomalies, transient transaminitis (Hematol Oncol Clin North Am 2009;23:233)
• Amegakaryocytic thrombocytopenia: Isolated thrombocytopenia
Pure RBC Aplasia (Pediatr Rev 2002;23:111) will have reticulocytopenia
• Diamond–Blackfan (Consensus conference: Br J Haematol 2008;142:859)
• Insidious presentation in 1st yr of life (2–3 mo)
• 25% w/ dysmorphic features (short statues, abnormal facies w/ cleft palate),
abnormalities of the thumb, congenital heart disease
• Increased MCV and red cell adenosine deaminase
• Rx: Glucocorticoids (initially prednisone 2 mg/kg/d) and check retic response
• If no response to steroids, will likely need chronic RBC transfusion support
• If matched sibling, consider BMT
• Complications of chronic transfusions: Iron overload and need chronic iron
chelation therapy. Increased risk of AML
• Transient erythroblastopenia of childhood (TEC)
• Unknown etiology; median age is 2 yr; normal physical exam
• Resolves spont w/i mo. Recurrence unlikely; can require RBC xfusion
• Parvovirus: Significant in prenatal parvo infxn or setting of chronic hemolysis (sickle cell)
• Has affinity for erythroid precursors; thus in setting of chronic hemolysis and incr reticulocytosis, can lead to severe anemia and aplastic crisis
Bone Marrow Transplant (N Engl J Med 2006;354:1813;
Pediatr Clin North Am 2010;57:147)
• Definitions
• Graft vs. host disease (GVHD): Undesirable side effect of allogenic hematopoietic stem cell transplant (HSCT) where donor cells effect the host
• Graft vs. tumor (GVT) effect: Desired effect of bone marrow transplant, transplanted
cells attack host tumor cells
• Goal is to balance immunosuppression as to minimize the effects of GVHD, while still maintaining an adequate GVT response
• Indications
• Malignancy: Useful in case of refractory dz or non-responsive to usual chemo Rx regimens. Uses GVT effect w/ hopes of eradicating malignancy
• Non-malignant dzs: Immunodeficiencies, hematologic abn (thalassemia, sickle cell); goal to replace abn lymphohematopoietic system w/ nml donor one
• Autologous: Goal is as rescue for pt w/o replacing their lymphohematopoietic sys
• Allows pts to receive higher than usual doses of chemo w/ rescue in place
• Often used for neuroblastoma, extraocular retinoblastoma
• No risk of GVHD, but also no benefit of GVT
• Allogeneic: Donor provides host w/ hematopoietic rescue and GVT effect
• Goal to minimize side effect of GVHD and maximize GVT effect