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544 Part VI: The Erythrocyte Chapter 36: Pure Red Cell Aplasia 545

parvovirus infection should be suspected in the anemic cancer patient for convenience usually is transfused as 2 units every 2 weeks. The goal
after stem cell transplantation, in patients treated with immunosup- of preventing symptoms of anemia is achievable in most patients if the
pressive drugs, in patients with AIDS, and in patients with a family or nadir hemoglobin is greater than 7 g/dL (70 g/L). A goal greater than
personal history suggestive of inherited immune disorder. Other viral 9 g/dL (90 g/L) may be preferable in patients with cardiac or pulmonary
infections have been implicated in pure red cell aplasia, including infec- disease and in older patients. Even refractory pure red cell aplasia is
tious mononucleosis and an unknown agent in seronegative hepatitis. consistent with a prolonged and perhaps even normal life expectancy,
and iron-chelation therapy can be initiated based on the ferritin level
(Chap. 43).
LABORATORY FEATURES Immunosuppression Immunosuppressive agents are used to
Anemia is either normocytic or macrocytic, reticulocytopenia is pro- treat disease of suspected immune origin. Response is likely in the
found, and white cell and platelet counts are generally normal. The majority of patients, but sequential treatment with a variety of agents
marrow shows absent or very few erythroid precursor cells, but nor- often is required. Some patients, however, remain refractory to treat-
mal granulopoiesis and megakaryocytopoiesis. Iron saturation and ment. 119,164–166 Typically, oral prednisone 1 to 2 mg/kg/day is given first,
ferritin level frequently are elevated and rise further after repeated red and about half of patients improve. A 1- to 2-month trial can be asso-
cell transfusions. Erythroid colony assays may predict responsiveness ciated with significant toxicity and evidence of Cushing syndrome.
to immunosuppressive treatment. The presence of marrow or blood Higher response rates have been cited for cyclosporine, and some
BFU-E and CFU-E correlates with hematologic improvement, 130,158,159 investigators advocate using this drug first. 53,167–171 Cytotoxic agents,
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but these tests may not be generally available. especially azathioprine and cyclophosphamide, can be beneficial
Thymomas are frequently associated with autoimmune disease, but are not first-choice because of their mutagenic and leukemogenic
myasthenia gravis most prominently and occasionally with marrow fail- properties. These drugs may be preferred for red cell aplasia associated
ure syndromes. In pure red cell aplasia, a thymoma should be sought with LGL, in which cytoreduction is required. 124,173,174 Acquired pure
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by chest imaging, including computed tomographic scan. The associ- red cell aplasia often responds to antithymocyte globulin. 130,159,175 More
ation of thymoma and pure red cell aplasia has been emphasized but specific monoclonal antibodies have less toxicity than does antilym-
is uncommon: thymoma in only two of 37 red cell aplasia patients, phocyte globulin, and can be administered without hospitalization.
176
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and only two instances of red cell aplasia in a series of 29 thymoma Daclizumab, a monoclonal antibody directed against the IL-2 receptor,
patients. The thymomas usually are encapsulated and have a spindle is effective in approximately 40 percent of patients. Success has been
177
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cell histology. In one series, 10 of 56 cases were considered malignant reported also using rituximab (anti-CD20 monoclonal antibody) 178–180
because of their locally infiltrating character ; therefore, the tumors and alemtuzumab (anti-CD52). 181–183 Some patients with resistant dis-
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should be surgically excised, if feasible. ease respond to fludarabine and cladribine. 184,185 Plasmapheresis 186,187
CLL should be evident based on elevated lymphocyte count and has produced long-lasting improvement in a few patients, presumably
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immunophenotyping for monoclonality. LGL (Chap. 94), which fre- by removing pathogenic antibodies. The absence of randomized trials
quently underlies red cell aplasia, may be more subtle. It’s diagnosis and even case series of adequate sample size makes the extrapolation of
requires careful examination of the blood film for typical lymphocytic case reports to quantitative estimates of response problematic for many
forms, flow cytometry for cell surface markers characteristic of natural of these therapies. 164
killer and cytotoxic lymphocytes, and demonstration of monoclonal A thymoma should be excised to prevent local spread of a malig-
T-cell proliferation by molecular studies. nant tumor, but thymectomy does not necessarily improve marrow
Persistent parvovirus infection can be difficult to diagnose. Giant function. Red cell aplasia can follow thymectomy. Cyclosporine
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pronormoblasts scattered on the marrow film are the most character- appears the most effective drug to treat pure red cell aplasia associated
istic of the condition (see Fig. 36–1), but such typical cells may not be with thymoma. Red cell aplasia is rarely an indication for stem cell
188
observed. Marrow morphologies that are dysplastic or suggestive of leu- transplantation because the anemia usually can be managed with less
kemia also have been described. Serum antibodies specific to the virus drastic approaches. Unresponsive patients have been cured by infusion
are absent or only IgM is positive. Parvovirus DNA should be present of allogeneic stem cells after cyclophosphamide conditioning. 189,190
in high concentrations in the blood and readily detected by molecular Other Therapies Despite early favorable case reports, androgens,
techniques. erythropoietin, and splenectomy are not routinely used to treat pure red
cell aplasia.
Immunoglobulin for Persistent B19 Parvovirus Infection Per-
DIFFERENTIAL DIAGNOSIS sistent parvovirus infection results from the inability of the host to
Distinction between inherited and acquired red cell aplasia may be mount an effective humoral immune response. It can be effectively
impossible in the younger patient. Rarely, pure red cell aplasia is diffi- treated in almost all cases by administration of commercial immuno-
cult to distinguish from more generalized marrow failure if other blood globulin, 191,192 an excellent source of neutralizing antibodies present in a
counts are borderline. A dysmorphic marrow smear and abnormal large proportion of the normal population. Infusion of immunoglobulin
chromosomes point to myelodysplasia as responsible for isolated ane- at 0.4 g/kg/day for 5 to 10 days should produce brisk reticulocytosis and
mia and reticulocytopenia. B19 parvovirus infection should always be restore a hemoglobin level appropriate for the patient. A single course
suspected and searched for in any immunosuppressed individual who is may be adequate to cure longstanding red cell aplasia resulting from an
anemic because the infection can be treated. underlying inherited immunodeficiency syndrome, but patients with
193
AIDS may not show complete clearance of parvovirus from the circu-
147
THERAPY, COURSE, AND PROGNOSIS lation and may relapse, requiring retreatment or maintenance immu-
Patients suffering from persistent
147,194
noglobulin injections (Fig. 36–2).
Treatment B19 parvovirus infection do not have typical manifestations of a viral
Transfusion Therapy As with inherited red cell aplasia, transfusions infection, such as fever. In these patients, immunoglobulin infusions
and iron chelation are basic to management. In an adult, 1 unit of can induce fifth disease symptoms of variable severity, including cuta-
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packed erythrocytes per week can replace marrow erythropoiesis, which neous eruptions and arthritis. Older case reports of red cell aplasia

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