Hematopoietic Cell Transplantation (HCT) involves the intravenous (IV) infusion of allogeneic (donor) or autologous stem cells to reestablish hematopoietic function in individuals whose bone marrow or immune system is damaged or defective. They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates.

Several inherited and acquired conditions have the potential for severe and/or progressive disease. For some conditions, allogeneic hematopoietic cell transplantation (HCT) has been used to alter the natural history of the disease or potentially offer a cure.

Autoimmune diseases arise from an abnormal response of the body against substances and issues normally present in the body. For some conditions, autologous HCT has been used as a treatment.

Inherited and Acquired Conditions

Allogeneic HCT may be considered medically necessary for select individuals with ANY of the following disorders: 

• Hemoglobinopathies
  • Sickle cell anemia for children or young adults with either a history of prior stroke or at increased risk of stroke or end-organ damage; or
  • Homozygous beta-thalassemia (i.e., thalassemia major); or
• Bone marrow failure syndromes
  • Aplastic anemia including hereditary (including Fanconi anemia, dyskeratosis congenita, Schwachman-Diamond syndrome, Diamond-Blackfan syndrome); or 
  • Acquired (i.e., secondary to drug or toxin exposure) forms; or
• Primary immunodeficiencies
  • Absent or defective T-cell function (i.e., severe combined immunodeficiency, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome); or
  • Absent or defective natural killer function (i.e., Chediak-Higashi syndrome); or
  • Absent or defective neutrophil function (i.e., Kostmann syndrome, chronic granulomatous disease, leukocyte adhesion defect); or
• Inherited metabolic disease
  • Lysosomal and peroxisomal storage disorders EXCEPT for Hunter, Sanfilippo, and Morquio syndromes; or  
• Genetic disorders affecting skeletal tissue
  • Infantile malignant osteopetrosis (i.e., Albers-Schonberg disease or marble bone disease).

Allogeneic HCT not meeting the criteria as indicated in this policy is considered not medically necessary.

The following guidelines list the immunodeficiencies that have been successfully treated by allo-HCT:

• Lymphocyte immunodeficiencies
  • Adenosine deaminase deficiency
  • Artemis deficiency
  • Calcium channel deficiency
  • CD 40 ligand deficiency
  • Cernunnos/X-linked lymphoproliferative disease deficiency
  • CHARGE syndrome with immune deficiency
  • Common gamma chain deficiency
  • Deficiencies in CD45, CD3, CD8
  • DiGeorge syndrome
  • DNA ligase IV deficiency syndrome
  • Interleukin-7 receptor alpha deficiency
  • Janus-associated kinase 3 (JAK3) deficiency
  • Major histocompatibility class II deficiency
  • Omenn syndrome
  • Purine nucleoside phosphorylase deficiency
  • Recombinase-activating gene (RAG) 1/2 deficiency
  • Reticular dysgenesis
  • Winged helix deficiency
  • Wiskott-Aldrich syndrome
  • X-linked lymphoproliferative disease
  • Zeta-chain-associated protein-70 (ZAP-70) deficiency
•  Phagocytic deficiencies
  • Chédiak-Higashi syndrome
  • Chronic granulomatous disease
  • Hemophagocytic lymphohistiocytosis
  • Griscelli syndrome, type 2
  • Interferon-gamma receptor deficiencies
  • Leukocyte adhesion deficiency
  • Severe congenital neutropenias
  • Shwachman-Diamond syndrome
• Other immunodeficiencies
  • Autoimmune lymphoproliferative syndrome
  • Cartilage hair hypoplasia
  • CD25 deficiency
  • Hyper IgD and IgE syndromes
  • Immunodeficiency, centromeric instability, and facial dysmorphism syndrome (ICF syndrome)
  • Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX syndrome)
  • Nuclear factor-κ B (NF-κB) essential modulator deficiency 
  • NF-κB inhibitor, NF-KB-a  deficiency
  • Nijmegen breakage syndrome

For inherited metabolic disorders, allogeneic HCT has been proven effective in some cases of Hurler, Maroteaux-Lamy, and Sly syndromes, childhood onset cerebral X-linked adrenoleukodystrophy, globoid-cell leukodystrophy, metachromatic leukodystrophy, alpha-mannosidosis, and aspartylglucosaminuria. Allogeneic HCT is possibly effective for fucosidosis, Gaucher types 1 and 3, Farber lipogranulomatosis, galactosialidosis, GM1, gangliosidosis, mucolipidosis II (I-cell disease), multiple sulfatase deficiency, Niemann-Pick, neuronal ceroid lipofuscinosis, sialidosis, and Wolman disease. Allogeneic HCT has not been effective in Hunter, Sanfilippo, or Morquio syndromes. 

The experience with reduced-intensity conditioning (RIC) and allogeneic HCT for the diseases listed in this policy has been limited to small numbers of individuals and have yielded mixed results, depending upon the disease category. In general, the results have been most promising in the bone marrow failure syndromes and primary immunodeficiencies. In the hemoglobinopathies, success has been hampered by difficulties with high rates of graft rejection, and in adult individuals, severe graft-versus-host-disease (GVHD).

Autoimmune Diseases

Autologous HCT may be considered medically necessary as a treatment of systemic sclerosis/scleroderma when ALL the following criteria are met:

• The individual is less than 60 years of age; and  
• Maximum duration of condition of five (5) years; and
• Modified Rodnan Scale Scores is greater than or equal to 15; and
• History of less than six (6) months treatment with cyclophosphamide; and
• No active gastric antral vascular ectasia; and
• Individual does NOT have ANY of the following exclusions:
  • Cardiac
    • Left ventricular ejection fraction less than 50%; or
      • Tricuspid annular plane systolic excursion less than 1.8 cm; or
        • Pulmonary artery systolic pressure greater than40 mm Hg; mean pulmonary artery pressure greater than 25 mm Hg; or
  • Pulmonary
    • Diffusing capacaity of carbon monoxide (DLCo) less than 40% of predicted value; or
      • Forced vital capacity (FVC) less than 45% of predicted value; or
  • Renal:
    • Creatinine clearance less than 40 ml/minute.

Individual with systemic sclerosis and internal organ involvement indicated by the following measurements may be considered medically necessary for autologous HCT:

• Cardiac:
  • Abnormal electrocardiogram; or
• Pulmonary:
  • DLCo less than 80% of predicted value; or
  • Decline of FVC of greater than or equal to 10% in last 12 months; or
  • Pulmonary fibrosis; or
  • Ground glass appearance on high resolution chest computed tomography (CT); or
• Renal:
  • Scleroderma-related renal disease.

Autologous HCT for systemic sclerosis/scleroderma not meeting the criteria as indicated in this policy is considered not medically necessary.

Allogeneic HCT or autologous HCT to treat the following autoimmune diseases is considered not medically necessary (this is not an all-inclusive list):

• Multiple sclerosis; and
• Systemic lupus erythematosus; and
• Juvenile idiopathic or rheumatoid arthritis; and
• Chronic inflammatory demyelinating polyneuropathy; and
• Type 1 diabetes.

HCT to treat non-cancer diseases is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.