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MKSAP: 78-year-old woman with increasing fatigue

mksap
Conditions
April 21, 2012
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 78-year-old woman has a 3-month history of increasing fatigue. She has no other medical problems and does not take any medications.

On physical examination, temperature is normal, blood pressure is 130/80 mm Hg, pulse rate is 72/min, and respiration rate is 16/min. The patient appears pale. Examination is unremarkable.

Laboratory studies:

Hemoglobin 7.8 g/dL (78 g/L)
Leukocyte count 2800/µL (2.8 × 109/L)
Absolute neutrophil count 1200/µL (1.2 × 109/L) (normal >1500/µL [1.5 × 109/L])
Platelet count 560,000/µL (560 × 109/L)
Erythropoietin 600 mU/mL (600 U/L)

Bone marrow examination shows hypercellular marrow with erythroid hyperplasia and dysplasia of the erythroid and granulocyte series. Megakaryocytes are increased with many hypolobulated cells. Iron stores are normal. Cytogenetic studies show deletion of the long arm of chromosome 5 [del(5q-)].

Which of the following is the most appropriate treatment?

A) Azacitidine
B) Danazol
C) Lenalidomide
D) Granulocyte colony-stimulating factor and recombinant erythropoietin

MKSAP Answer and Critique

The correct answer is C) Lenalidomide. This item is available to MKSAP 15 subscribers as item 15 in the Hematology and Oncology section. More information about MKSAP 15 is available online.

This patient should receive lenalidomide. Myelodysplastic syndromes (MDS) are clonal disorders of the hematopoietic stem cells that occur predominantly in patients older than 50 years and are characterized by ineffective hematopoiesis and peripheral cytopenia. Dysplasia of erythroid, granulocytic, or megakaryocytic lineages in a patient with a hypercellular bone marrow and low peripheral blood counts suggests MDS. Detection of clonal abnormalities commonly involving chromosomes 3, 5, 7, 8, and 17 supports the diagnosis. This patient has the 5q- syndrome (interstitial deletion of the long arm of chromosome 5), which is a subtype of MDS, characterized by an elevated platelet count and anemia. Most patients are elderly women who have an indolent course associated with transfusion-dependent anemia, a low incidence of neutropenia and thrombocytopenia, and a low rate of transformation to acute myeloid leukemia. This subtype of MDS responds favorably to lenalidomide, an analogue of thalidomide, which results in resolution of the anemia in two thirds of patients. Lenalidomide is U.S. Food and Drug Administration-approved for patients with the 5q- syndrome, but they must register with the “Revassist” program, and they must complete an informed consent to ensure that they understand the need to minimize fetal exposure. Lenalidomide can cause neutropenia and infections, and blood counts must be monitored closely.

Patients with classic MDS treated with azacitidine have better outcomes than patients who receive supportive care only. In these patients, azacitidine therapy significantly delays leukemic transformation and significantly improves quality of life. Azacitidine is not as effective as lenalidomide for a patient with the 5q- syndrome. Danazol has been used to treat the anemia associated with MDS. However, danazol has a low response rate and many side effects (especially masculinizing effects in women) and is therefore not recommended as first-line therapy. In selected patients with MDS, co-administration of erythropoietin and granulocyte colony-stimulating factor has a synergistic effect in increasing hemoglobin levels and decreasing transfusion requirements, particularly in patients requiring less than 2 units of packed erythrocytes per month and in those with serum erythropoietin levels less than 500 U/L.

Key Point

  • Patients with the 5q- syndrome have a subtype of myelodysplastic syndrome that responds to lenalidomide.

Learn more about ACP’s MKSAP 15.

This content is excerpted from MKSAP 15 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 15 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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