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426 Part IV Disorders of Hematopoietic Cell Development

TABLE Classification of Pure Red Cell Aplasia Autoantibodies
32.1 Cytokine inhibition
Congenital (DBA) FasL
Primary Autoimmune IFN, TNF
Idiopathic
Secondary Thymoma 1–5 CLL 6,7
Hematologic T-LGL/chronic NK-LGL
malignancies leukemia 8–15
Erythroid
Myeloma 16 progenitors
NHL 17,18 TCR Direct cytotoxicity
MDS 19
ALL 20–22 PRCA Myeloid progenitors
Solid tumors Renal cell carcinoma 23 granulocytes
Thyroid cancer 24
Various AIN
adenocarcinomas 25,26
Infections Parvovirus B19 27
28
EBV, mumps
29
HIV, HTLV-1 12
CMV 30
Viral hepatitis (hepatitis Fig. 32.1 PATHOGENESIS OF PURE RED CELL APLASIA. AIN,
A, 31–33 hepatitis B 34,35 ) Autoimmune neutropenia; FasL, Fas ligand; IFN, interferon; PRCA, pure red
Leishmaniasis 36 cell aplasia; TCR, T-cell receptor; TNF, tumor necrosis factor.
Gram-positive systemic
infections (e.g.,
staphylococcemia) T-Cell Large Granular
Meningococcemia
Autoimmune SLE 37 Lymphocyte–Associated PRCA
conditions RA 38
Sjögren syndrome 39,40 Although neutropenia is a typical finding in T-LGL leukemia, PRCA
Mixed connective tissue with varying degrees of erythroblastopenia can also be observed in
disease 41 10% to 15% of patients with T-LGL leukemia. It is found to be
Autoimmune hepatitis 42 commonly associated with signal transducer and activator of tran-
Anti-EPO antibodies 43,44 scription (STAT)3 mutant T-LGL leukemia. In such a setting, PRCA
ABO-incompatible BMT is often accompanied by red cells with an increased mean corpuscular
Minor incompatibility 45–50 volume. It is possible that PRCA associated with T-LGL leukemia
Drugs and represents an extreme form of the T cell–mediated disease that, if
polyclonal, might be classified as idiopathic PRCA.
chemicals
Pregnancy 51,52
Severe nutritional Thymoma-Associated PRCA
deficiencies 53,54
Renal failure 55
Thymoma is associated with PRCA; thus a chest x-ray examination
ALL, Acute lymphoblastic leukemia; BMT, bone marrow transplantation; CLL, or computed tomographic (CT) scan should be included in the
chronic lymphocytic leukemia; CMV, cytomegalovirus; DBA, Diamond-Blackfan workup for PRCA. Antibodies with direct inhibitory effects against
anemia; EBV, Epstein-Barr virus; EPO, erythropoietin; HIV, human
immunodeficiency virus; HTLV-1, human T-lymphotrophic virus-1; MDS, erythroid precursors may be present. T cell–mediated inhibition of
myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; NK-LGL, natural erythropoiesis has also been implicated in the pathogenesis of PRCA
killer large granular lymphocyte; RA, refractory anemia; SLE, systemic lupus associated with either benign or malignant thymomas. A late onset
erythematosus; T-LGL, T-cell large granular lymphocyte.
immunodeficiency condition; Good syndrome characterized by
hypogammaglobulinemia and thymoma is associated with PRCA in
33% of the patients. Thymectomy is the usual initial treatment
approach; however, incomplete responders, nonresponders, and
SECONDARY FORMS OF PURE RED CELL APLASIA patients who relapse are common, necessitating additional therapies
in the form of azathioprine, intravenous immunoglobulin (IVIg), and
Clinical Associations cyclosporine A (CsA).

B-Cell Chronic Lymphocytic Pregnancy-Associated PRCA
Leukemia–Associated PRCA
Pregnancy-associated PRCA is a self-limited syndrome that may
In B-cell chronic lymphocytic leukemia (CLL), PRCA can be occur at any age of gestation. It has a high risk for relapse during
observed in up to 6% of cases. A recent study found 0.5% of their subsequent pregnancies and can be safely managed with either blood
1750 CLL patients has PRCA. The underlying pathogenetic mecha- transfusions or corticosteroids. Patients with other forms of PRCA
nisms are not clear, and the inhibition of the erythroid series does may also be more prone to relapse during pregnancy.
not appear to be mediated by a soluble factor. The distinction between
whether the PRCA is a result of the primary B-cell CLL disease or Parvovirus B19 and Other Viral-Induced PRCAs
its therapy becomes difficult in circumstances when PRCA presents Parvovirus B19 is a single-stranded deoxyribonucleic acid (DNA)
as a late event. In most cases, PRCA cannot be attributed simply to virus, which in normal individuals causes fifth disease (erythema
infiltration of the marrow by lymphoma cells. infectiosum) in children and arthropathy in adults. The cellular