Aetna considers allogeneic bone marrow or peripheral stem cell transplant medically necessary for the treatment of severe aplastic anemia when members meet the transplanting institution's selection criteria.  In the absence of a institution's selection criteria, Aetna considers allogeneic bone marrow or peripheral stem cell transplant medically necessary for the treatment of severe aplastic anemia when the member has at least three of the four following features:

1. Neutrophil count less than 0.5 x 109/L
2. Untransfused platelet count less than 20 x 109/L
3. Reticulocyte count less than 1% or less than 20 x 109/L (corrected for hematocrit)
4. Bone marrow cellularity less than 25% (markedly hypocellular).

Aplastic anemia (AA) is characterized by peripheral blood pancytopenia, resulting from a failure of the bone marrow to produce blood cells. In the United States, it has an age-adjusted incidence of 2.2 per million populations per year.  Pathogenic mechanisms for AA vary and include intrinsic defects of hematopoietic stem cells, defects in the marrow micro-environment, and abnormal humoral or cellular immune control of hematopoiesis. In most patients, AA is of unknown etiology (idiopathic), whereas in some, the disease can be secondary to infections, drugs or toxin exposure, and hereditary causes (e.g., Fanconi's anemia or Diamond-Blackfan syndrome). Severe AA is defined by the presence of neutrophils less than 0.5 x 10⁹/L, platelets less than 20 x 10⁹/L, reticulocytes less than 1%, and bone marrow cellularity less than 20%.  When three of four of these symptoms are present, the median survival without therapy is about 3 months, with only 20% of patients surviving for 12 months.  Currently, two definitive treatments are available for patients with severe AA: (i) IST that includes the use of anti-thymocyte globulin, cyclosporine, and cyclophosphamide; and (ii) allogeneic bone marrow transplantation (ABMT).  The benefits of each are comparable.  However, certain subsets of patients derive superior benefit from one or the other.

Allogeneic bone marrow transplantation from human leukocyte antigen (HLA)-matched, related donors is generally accepted as the initial treatment of choice for young patients (less than 20 years old). It results in the complete reconstitution of hematopoiesis, whereas autologous hematopoietic remissions after IST are more susceptible to relapse.  The literature indicates that survival rates after ABMT, in patients between the ages of 20 and 40, are comparable to those reported for IST.  Better survival rates after ABMT have been attained with improved conditioning regimens and graft-versus-host disease (GVHD) prophylaxis.  Best current results demonstrate long-term, event-free survivals with successful allografts on the order of 90%.  Long-term complications after ABMT include GVHD and secondary neoplasms.  The role of ABMT from an unrelated donor is being investigated.

For patients older than 40, the generally accepted treatment of choice is IST, which entails the combination of anti-thymocyte globulin and cyclosporin A.  A variable proportion of patients (ranging from 20 to 80%) respond to IST. However, although responses may be frequent, long-term outcome is guarded because some patients may relapse and others may develop a clonal disorder, including myelodysplasia, leukemia, or paroxysmal nocturnal hemoglobinuria. Long-term complications of IST include recurrence and development of clonal myeloid disorders.

In a review on ABMT for the treatment of AA, Horowitz (2000) stated that long-term survival rates ranged from less than 40 to more than 90% in reported series.  These rates have improved over the past 20 years due to significant reductions in GVHD, interstitial pneumonitis, and early transplant-related mortality.  Most long-term survivors have excellent performance status.  Late complications such as cataracts, thyroid disorders, joint problems, and therapy-related cancers are observed, especially in patients who received radiation for pre-transplant conditioning.  Results are best in young patients transplanted with bone marrow from a HLA-identical sibling; early transplantation is appropriate in this group.  For older patients or those without an HLA-identical related donor, transplants are better reserved for those who fail to respond to IST.

Kojima and co-workers (2000a) compared the long-term outcome of acquired AA in children treated with IST or ABMT. They recommended ABMT as first-line therapy in pediatric severe AA patients with an HLA-matched family donor. Alternative donor ABMT was recommended as salvage therapy in patients who relapsed or did not respond to initial IST. In a Consensus Conference on the Treatment of Aplastic Anemia, the participants recommended that the number of courses of IST for non-responders before unrelated ABMT consideration to be 1 for children and 2 for adults (Kojima et al, 2000b).