Hematopoietic stem cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in patients who receive bone marrow toxic doses of cytotoxic drugs with or without whole body radiation therapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). These cells can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates.
GENETIC DISEASES AND ACQUIRED ANEMIAS
Hemoglobinopathies
Thalassemia results from mutations in the globin genes, resulting in reduced or absent hemoglobin production and reduced oxygen delivery. The supportive treatment of beta-thalassemia major requires life-long red blood cell transfusions, which lead to progressive iron overload and the potential for organ damage and impaired cardiac, hepatic and endocrine function. The only definitive cure for thalassemia is to correct the genetic defect with allogeneic HSCT.
Sickle cell disease (SCD) is caused by a single amino acid substitution in the beta chain of hemoglobin, resulting in the formation of sickle-shaped red blood cells. Sickle cells break down prematurely, which can lead to anemia. Additionally, the sickle shape of the cells blocks the flow of blood through vessels and may manifest clinically with severe painful crises, acute chest syndrome, stroke, chronic pulmonary and renal dysfunction, growth retardation, neurologic deficits and premature death. Unlike thalassemia major, sickle cell disease may have a variable course of clinical severity. Three major therapeutic options are available: chronic blood transfusions, hydroxyurea and HSCT, the latter being the only possibility for cure.
Bone marrow failure syndromes
Aplastic anemia in children is rare and most often idiopathic. It is less commonly due to a hereditary disorder. Inherited syndromes include Fanconi Anemia (FA), a rare, autosomal recessive disease, characterized by genomic instability, with congenital abnormalities, chromosome breakage, cancer susceptibility and progressive bone marrow failure leading to pancytopenia and severe aplastic anemia. Frequently this disease terminates in a myelodysplastic syndrome or acute myelogenous leukemia.
Dyskeratosis congenita is characterized by marked telomere dysregulation with clinical features of reticulated skin hyperpigmentation, nail dystrophy and oral leukoplakia. Early mortality is associated with bone marrow failure, infections, pulmonary complications or malignancy.
Mutations affecting ribosome assembly and function are associated with Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Shwachman-Diamond has clinical features that include pancreatic exocrine insufficiency, skeletal abnormalities and pancytopenia. Diamond-Blackfan anemia is characterized by absent or decreased erythroid precursors in the bone marrow with 30% of patients also having a variety of physical anomalies.
Primary immunodeficiencies
The primary immunodeficiencies (PID) are a genetically heterogeneous group of diseases that affect distinct components of the immune system. More than 120 gene defects have been described, causing more than 150 disease phenotypes. The most severe defects (collectively known as severe combined immunodeficiency or SCID) cause an absence or dysfunction of T-lymphocytes, and sometimes B lymphocytes and natural killer cells. Without treatment, patients with SCID usually die by 12-18 months of age. With supportive care, including prophylactic medication, the life span of these patients can be prolonged, but long-term outlook is still poor, with many dying from infectious or inflammatory complications or malignancy by early adulthood. Bone marrow transplant is the only definitive cure, and is the treatment of choice for SCID and other PID including Wiskott-Aldrich syndrome and congenital defects of neutrophil function.
Inherited metabolic diseases (IMD)
Lysosomal storage disorders (LSD) consist of many different rare diseases caused by a single gene defect; most are inherited as an autosomal recessive trait. LSD are caused by specific enzyme deficiencies which result in defective lysosomal acid hydrolysis of endogenous macromolecules which subsequently accumulate as a toxic substance. Peroxisomal storage disorders (PSD) arise due to a defect in a membrane transporter protein which leads to defects in the metabolism of long-chain fatty acids. LSD and PSD affect multiple organ systems, including the central and peripheral nervous systems. These disorders are progressive and often fatal in childhood due to both the accumulation of toxic substrate and a deficiency of the product of the enzyme reaction. Hurler syndrome usually leads to premature death by five years of age.
Exogenous enzyme replacement therapy is available for a limited number of the IMD, however, these drugs don’t cross the blood-brain barrier, a factor which results in ineffective treatment of the central nervous system. Stem cell transplantation provides a constant source of enzyme replacement from the engrafted donor cells which are not impeded by the blood-brain barrier. The donor-derived cells can migrate and engraft in many organ systems, giving rise to different types of cells (e.g., microglial cells in the brain and Kupffer cells in the liver).
Infantile malignant osteopetrosis
Osteopetrosis is a condition caused by defects in osteoclast development and/or function. The osteoclast (the cell that functions in the breakdown and resorption of bone tissue) is known to be part of the hematopoietic family and shares a common progenitor with the macrophage in the bone marrow. Osteopetrosis is a heterogeneous group of heritable disorders, resulting in several different types of variable severity. The most severely affected patients are those with infantile malignant osteopetrosis. Patients with infantile malignant osteopetrosis suffer from dense bone, including a heavy head with frontal bossing, exophthalmos, blindness by approximately six months of age, and severe hematologic malfunction with bone marrow failure. HSCT is the only curative therapy for this fatal disease.
I. Allogeneic Hematopoietic Stem-Cell Transplantation
Allogeneic hematopoietic stem-cell transplantation may be considered MEDICALLY NECESSARY AND APPROPRIATE for selected patients with the following disorders:
Allogeneic hematopoietic stem-cell transplantation is considered EXPERIMENTAL/INVESTIGATIVE for treatment of Hunter, Sanfilippo and Morguio syndromes due to a lack of clinical evidence demonstrating an impact on improved health outcomes.
II. Autologous Hematopoietic Stem-Cell Transplantation
Autologous hematopoietic stem-cell transplantation is considered EXPERIMENTAL/INVESTIGATIVE for treatment of genetic diseases and acquired anemias due to a lack of clinical evidence demonstrating an impact on improved health outcomes.
III. Repeat Transplant
A second (allogeneic or autologous) hematopoietic stem-cell transplnatation (HSCT) is considered EXPERIMENTAL/INVESTIGATIVE for all indications, due to the lack of clinical evidence demonstrating an impact on improved health outcomes.
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Documentation Submission:
Link to Transplant Pre-Authorization Form: https://www.bluecrossmn.com/sites/default/files/DAM/2022-06/x16519r04-transplant-prior-authorization-request-form.pdf
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Acknowledgements:
CPT® codes copyright American Medical Association® 2022. All rights reserved.
CDT codes copyright American Dental Association® 2022. All rights reserved.
