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MKSAP: 24-year-old man with aplastic anemia

mksap
Conditions
November 18, 2012
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 24-year-old man undergoes follow-up evaluation for treatment of aplastic anemia. Two of his siblings are HLA-identical matches.

Laboratory studies:

Hemoglobin 8.3 g/dL (83 g/L) (following transfusion of 1 unit of irradiated packed erythrocytes last week)
Leukocyte count 500/µL (0.5 × 109/L) with 23% neutrophils, 3% band forms, and 71% lymphocytes
Platelet count 26,000/µL (26 × 109/L)
Reticulocyte count 0.2%

Review of the bone marrow biopsy done 2 weeks ago confirms the diagnosis of aplastic anemia, demonstrating an aplastic bone marrow with normal cytogenetics.

Which of the following is the most appropriate treatment?

A: Allogeneic hematopoietic stem cell transplantation
B: Antithymocyte globulin, corticosteroids, and cyclosporine
C: Autologous hematopoietic stem cell transplantation
D: Corticosteroids
E: Granulocyte colony-stimulating factor

MKSAP Answer and Critique

The correct answer is A: Allogeneic hematopoietic stem cell transplantation. This item is available to MKSAP 16 subscribers as item 2 in the Hematology/Oncology section.

MKSAP 16 released Part A on July 31. More information is available online.

The most appropriate treatment is allogeneic hematopoietic stem cell transplantation (HSCT). Aplastic anemia is classified by the severity of the neutropenia. Moderate aplastic anemia is diagnosed when the absolute neutrophil count (ANC) is 500 to 1000/µL (0.5 to 1.0 × 109/L). Severe aplastic anemia occurs when two or more of the following are present: ANC 200 to 500/µL (0.2 to 0.5 × 109/L), platelet count less than 20,000/µL (20 × 109/L), and reticulocyte count less than 0.2%. Very severe aplastic anemia is diagnosed when the ANC is less than 200/µL (0.2 × 109/L). ANC is calculated as leukocyte count × percentage of polymorphonuclear cells + band forms. This patient has very severe aplastic anemia. Patients with severe aplastic anemia who have an HLA-identical sibling and are younger than 40 years should be offered allogeneic HSCT as initial therapy. Because of the high mortality rate associated with this procedure, HSCT is generally not recommended as initial therapy for patients older than 40 years or those who are not medically fit to undergo transplantation or who have no HLA-identical sibling; these patients are typically treated with antithymocyte globulin and cyclosporine as initial therapy. Because this patient is young, healthy, and has two siblings who are an HLA-identical match, he should be offered allogeneic transplantation as initial therapy.

In some clinical trials of patients who are not transplant candidates, intravenous antithymocyte globulin plus corticosteroids and cyclosporine can result in partial and complete responses in 60% to 80% of patients. Many of these patients become transfusion independent, although response is often delayed for 3 to 6 months, and relapses can occur when the cyclosporine is tapered.

Autologous HSCT would not be an appropriate treatment choice because this patient has an essentially acellular bone marrow.

Prednisone as a single agent produces a very low response rate in patients with aplastic anemia.

Growth factors such as granulocyte colony-stimulating factor should not be given as primary therapy for aplastic anemia, and the use of growth factors as concomitant therapy is controversial. These agents are expensive, and some reports suggest a lower response rate to immunosuppressive therapy and a higher relapse rate when granulocyte colony-stimulating factor is used.

Key Point

  • Patients with severe aplastic anemia who have an HLA-identical sibling and are younger than 40 years should be offered allogeneic hematopoietic stem cell transplantation as initial therapy.

Learn more about ACP’s MKSAP 16.

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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