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Chapter 32 Acquired Disorders of Red Cell, White Cell, and Platelet Production 429

Medical
techniques) may show high levels of the virus at 10 genome copies
118
per milliliter, but it is important to note that serologic (IgM and
IgG) titers are usually absent. Erythropoietin antibodies, antinuclear Supportive
antibodies, and/or complement consumption may point toward a
specific disease mechanism. A radiographic workup may also be Supportive care includes blood transfusions and iron chelation.
useful in the clinical workup because chest x-ray examination or CT
scan may show evidence of a thymoma.
Immunosuppression
DIFFERENTIAL DIAGNOSIS Prednisone therapy is associated with significant response rates
(approximately 40%) and should constitute the initial therapeutic
PRCA can be easily differentiated from aplastic anemia and other approach. Initial responses are generally observed after 4 to 6 weeks.
types of bone marrow failure syndromes. A distinction between MDS A slow taper of prednisone is suggested over a period of 3 to 4
with erythroid hypoplasia and idiopathic PRCA may be more diffi- months. The disease may relapse, and the minimal maintenance dose
cult. In childhood, TEC has to be distinguished from DBA, but a of corticosteroids may need to be established to maintain the desired
history of normal blood counts, late onset of manifestations, and a Hb levels. Trials of prednisone therapy without clinical response
transient disease course are characteristic of TEC. longer than 8 weeks are not warranted.
Alternative therapies may include cyclosporine, oral cyclophos-
phamide, azathioprine, antithymocyte globulin (ATG), rituximab,
THERAPY and alemtuzumab (see Table 32.3). Erythropoietin and darbepoietin
are usually not effective as a sole agent but may hasten recovery
The distinction between primary and secondary forms of PRCA is following an adequate trial of cyclophosphamide. No randomized
essential because many secondary types have specific and very effec- trials exist to favor a particular treatment based on efficacy.
tive therapies (Table 32.3). All potentially offending drugs should be The choice of therapy may be influenced by clinical clues. For
discontinued, and drug-associated PRCA should remit within 3 to 4 example, the presence of LGLs may suggest the use of CsA,
weeks. Nutritional deficiencies (B 12 and folic acid) should be excluded hypogammaglobulinemia may be corrected with IVIg, whereas
and treated if present. The therapy of primary and secondary forms detection of hypergammaglobulinemia or monoclonal protein may
of PRCA refractory to the treatment of an underlying disease may be suggest a choice of rituximab. Most refractory cases may require
challenging and should include a sequential trial of various immuno- administration of ATG. The age of the patient may influence the
suppressive agents until a response is achieved. Spontaneous remis- choice of the cytotoxic agent, which may pose a significant risk
sions have been reported. for the development of secondary leukemias, especially with a
prolonged administration.
Danazol is a synthetic attenuated androgen that has been used for
Surgery or Radiation many years for the treatment of a variety of hematologic disorders,
mainly myelofibrosis.
In cases associated with thymoma, thymectomy is the usual initial IVIg is also effective in several types of PRCA. Higher doses of
treatment of choice before immunosuppression and may induce usually 2 g/kg of IVIg for 5 days are necessary for the treatment of
remission with return of erythropoiesis in 4 to 8 weeks in about 30% parvovirus B19 virus–induced PRCA. In AIDS patients with parvo-
to 40% of patients. Patients who fail to respond to surgery should be virus B19 virus–induced PRCA, a regimen consists of induction
treated as patients with idiopathic PRCA. The removal of a thymoma therapy with 1 g/kg daily for 1–2 days followed by 1 g/kg for 2 days.
may improve responsiveness to immunosuppressive therapy. Thymec- Azathioprine is an imidazolyl derivative of mercaptopurine
tomy in the absence of a thymoma in other forms of PRCA is not that inhibits DNA synthesis by inhibition of purine metabolism.
recommended. In circumstances where surgical resection of thymoma In PRCA, it may be given at a dose of 2–3 mg/kg/day IV and
is contraindicated, radiation therapy with or without chemotherapy has been found to be effective in patients nonresponsive to
may be administered. cyclophosphamide.

TABLE Therapy for Pure Red Cell Aplasia and Its Results
32.3
Study
Agent Chikkappa 119 Means 120 Au 121 Dessypris 122 Zecca 123 Lacy 124 Charles 125 Sloand 126 Abkowitz 127
Steroids 18/41 9/29 9/36 –
Cytotoxic 24/54 14/29 8/27 –
agents
Antithymocyte 2/6 0/1 8/12 6/6
globulin
Cyclosporine A 6/7 6/9 3/4 4/5 2/3
Splenectomy 4/23 0/1 0/1
Daclizumab 6/15
(Zenapax)
Rituximab 1/1
Alemtuzumab 2/2
(Campath)
Methotrexate 2/37