Bone Marrow Failure Treatment & Management

Supportive care is essential for patient survival. In patients with bone marrow failure, the resulting cytopenia can lead to life-threatening symptoms.

Anemia can cause fatigue and can impair the patient's ability to function in daily activities. Impaired heart function can be aggravated into congestive heart failure by increasing oxygen demands on the heart and other tissues.

If clinically indicated, initiate a blood transfusion using specific cells, such as packed red cells for anemia and platelets for thrombocytopenia. Clinical indications for red cell transfusions are symptoms secondary to anemia and, for platelets, bleeding from thrombocytopenia. Supportive care gives only temporary relief of symptoms and does not treat the primary disease.

Bone marrow transplantation (BMT) candidates are patients who are younger than age 55 years who have severe disease and a matched, related donor. ^[12] With current BMT regimens, most patients with severe aplastic anemia have a 60-70% long-term survival rate. Survival rates of higher than 80% are reported for patients in more favorable subgroups. Using matched, unrelated donors is less favorable (11-20% survival rates).

Patients with inherited bone marrow failure and a matched sibling are excellent candidates for hematopoietic stem cell transplantation (HSCT). A caveat is the patients’ extraordinary sensitivity to chemotherapeutic agents and radiation used in conditioning regimens, which must both be reduced to avoid fatal toxicities. Consider saving cord blood from healthy siblings when identified.

Consultations

Hematologists should manage patients with bone marrow failure. Additionally, an infectious disease specialist may be necessary. In severe cases, early consideration for BMT should be initiated. 

Infections resulting in neutropenia should be treated as emergencies. After blood cultures and other diagnostic cultures are obtained, broad-spectrum antibiotics that cover most common gram-positive and gram-negative organisms should be started empirically in patients with febrile neutropenia. With the new broad-spectrum antibiotics, a single antibiotic generally is sufficient. The choice can be altered later, depending on the results of sensitivity tests from positive cultures.

Sepsis, pneumonias, urinary tract infections, and cellulitis with bacterial organisms are common complications of neutropenia. The risk is moderate with actual or total neutrophil counts of 500-1000/μL, and the risk is high at levels below 500/μL.

The addition of antifungal agents should be considered in patients with persistent fever despite adequate antibacterial coverage. Liposomal amphotericin B is indicated if kidney dysfunction is present, because of the toxicity of the original formulation of the drug.

Patients with severe aplastic anemia who receive antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) but do not receive BMT have a 41% response rate and a 1-year survival rate of 55%. ^[13]  ATG or ALG should be given with corticosteroids to prevent serum sickness.

High-dose corticosteroids, such as methylprednisolone 20 mg/kg/day with rapid taper, have been administered in countries where ATG or ALG is expensive; response rates are 38%. Cyclosporine therapy at 200-400 mg/day (maintain serum trough levels at 100-250 ng/mL) has a reported 85% hematologic remission rate.

Androgens were used in the past, as the addition of androgens increases response rates to 70%, with a 1-year survival rate of 76%. However, most androgens are masculinizing and poorly tolerated by females and children. A variety of androgen formulations have been used, from testosterone propionate and nandrolone decanoate to oxymetholon and oxandrolone. Danazol is a nonmasculinizing androgen that may be useful. The response rate is limited to approximately 45%, and results may require 6-10 months of therapy. Androgen treatment may result in liver dysfunction, adenomas, and adenocarcinomas, and patients should have liver function tests performed every 3 to 6 months and hepatic lesions assessed by ultrasonography every 6 months. Hematologic responses to oxymetholone and danazol are comparable, but liver toxicity appears to be more common with oxymetholone. ^[14]

Hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), may be useful in patients with neutropenia who have infections, without requiring a white blood cell transfusion.

Mucosal bleeding from the nose, gums, or teeth may be easily controlled with oral aminocaproic acid (Amicar, 500-mg tablet or 500 mg/mL elixir). The dose of aminocaproic acid can be as high 6-8 g/day, in divided doses every 6-8 hours. Hypotension is the dose-limiting adverse effect. Disseminated intravascular coagulation (DIC) and clots in the urinary tract are contraindications. This therapy is useful in the long-term maintenance of severe thrombocytopenia in patients with bone marrow failure.

Transfuse packed red cells to maintain hemoglobin levels at 7-10 g/dL. Patients with coronary artery disease may need to be maintained at 10-12 g/dL if they are symptomatic at lower levels of hemoglobin. The benefits of red cell transfusions are limited to 1 month because the life span of transfused red blood cells is limited to the average life span of collected cells. One should also consider the associated risks of blood cell transfusions including iron overload and the risk of infection, although the latter is small.

Bleeding/hemorrhage resulting from thrombocytopenia is a major problem and may be life-threatening if it occurs intracranially. Platelet transfusions are effective for stopping acute bleeding. Unfortunately, the platelet life span is short and therefore the effect of platelet transfusions last only 2-4 days. This treatment temporarily stops bleeding but is not a practical maintenance therapy. Furthermore, patients can become refractory to platelet transfusions if they develop alloantibodies.