| MP 8.01.22 | Allogeneic Hematopoietic Stem-Cell Transplantation for Genetic Diseases and Acquired Anemias | |
| Medical Policy | ||
| Section Therapy |
Original Policy Date 12/1/99 |
Last Review Status/Date Reviewed with literature search/9:2009 |
| Issue 9:2009 |
Return to Medical Policy Index |
Disclaimer
Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
Description
Hematopoietic Stem-Cell Transplantation
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. Allogeneic HSCT refers to the use of hematopoietic progenitor cells obtained from a donor. They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Cord blood is discussed in greater detail in policy No. 7.01.50.
Immunologic compatibility between infused stem cells and the recipient is a critical factor for achieving a good outcome of allogeneic HSCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the Class I and Class II loci on chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci (with the exception of umbilical cord blood).
Preparative Conditioning for Allogeneic Hematopoietic SCT
The conventional practice of allogeneic HSCT involves administration of myelotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to cause bone marrow failure. Reduced-intensity conditioning (RIC) refers to chemotherapy regimens that seek to reduce adverse effects secondary to bone marrow toxicity. These regimens partially eradicate the patient’s hematopoietic ability, thereby allowing for relatively prompt hematopoietic recovery. Patients who undergo RIC with allogeneic HSCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism. A number of different cytotoxic regimens, with or without radiotherapy, may be used for RIC allotransplantation. They represent a continuum in their intensity, from nearly totally myeloablative, to minimally myeloablative with lymphoablation.
GENETIC DISEASES AND ACQUIRED ANEMIAS
Hemoglobinopathies
The thalassemias result from mutations in the globin genes, resulting in reduced or absent hemoglobin production, reducing oxygen delivery. The supportive treatment of beta-thalassemia major requires life-long red blood cell transfusions which leads to progressive iron overload and the potential for organ damage and impaired cardiac, hepatic and endocrine function. (1) 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, and unlike thalassemia major, has a variable course of clinical severity. (1) SCD typically manifests clinically with anemia, severe painful crises, acute chest syndrome, stroke, chronic pulmonary and renal dysfunction, growth retardation, neurologic deficits and premature death. The mean age of death for patients with SCD has been demonstrated as 42 years for males and 48 for females. Three major therapeutic options are available: chronic blood transfusions, hydroxyurea and HSCT, the latter being the only possibility for cure. (1)
Bone marrow failure syndromes
Aplastic anemia in children is rare, and is most often idiopathic and 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. Most patients with FA succumb to the complications of severe aplastic anemia, leukemia or solid tumors, with a median survival of 30 years of age. (2)
Dyskeratosis congenita is characterized by marked telomere dysregulation with clinical features of reticulated skin hyperpigmentation, nail dystrophy and oral leukoplakia. (3) Early mortality is associated with bone marrow failure, infections, pulmonary complications or malignancy. (3)
Mutations affecting ribosome assembly and function are associated with Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. (3) 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. (3)
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. (4) 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. (4) 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. (4) Bone marrow transplant is the only definitive cure, and the treatment of choice for SCID and other PID including Wiskott-Aldrich syndrome and congenital defects of neutrophil function. (5)
Inherited metabolic diseases (IMD)
Lysosomal storage disorders (LSD) consist of many different rare diseases caused by a single gene defect and most are inherited as an autosomal recessive trait. (6) 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. (6) Hurler syndrome usually leads to premature death by 5 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, 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. (6) The donor-derived cells can migrate and engraft in many organ systems, giving rise to different types of cells, for example microglial cells in the brain and Kupffer cells in the liver. (6)
Allogeneic HSCT has been used primarily to treat the IMD that belong to the lysosomal and peroxisomal storage disorders, as listed in Table 1. (6) The first stem cell transplant for an IMD was in 1980 in a patient with Hurler syndrome. Since that time, over 1,000 transplants have been performed worldwide. (6)
Table 1. Lysosomal and Peroxisomal Storage Disorders
| Category | Diagnosis | Other Names |
| Mucopolysaccharidosis (MPS) | MPS I MPS II MPS III A-D MPS IV A-B MPS IV MPS VII |
Hurler, Scheie, H-S Hunter Sanfililppo A-D Morquio A-B Maroteaux-Lamy Sly |
| Sphingolipidosis | Fabry’s Farber’s Gaucher’s I-III GM1 gangliosidosis Niemann-Pick disease A and B Tay-Sachs disease Sandhoff’s disease Globoid leukodystrophy Metachromatic leukodystrophy |
Lipogranuomatosis Krabbe disease MLD |
| Glycoproteinosis | Aspartylglucosaminuria Fucosidosis alpha-Mannosidosis beta-Mannosidosis Mucolipidosis III and IV |
Sialidosis |
| Other lipidoses | Niemann-Pick disease C Wolman disease Ceroid lipofuscinosis |
Type III-Batten disease |
| Glycogen storage | GSD type II | Pompe |
| Multiple enzyme deficiency | Galactosialidosis Mucolipidosis type II |
I-cell disease |
| Lysosomal transport defects | Cystinosis Sialic acid storage disease Salla disease |
|
| Peroxisomal storage disorders | Adrenoleukodystrophy Adrenomyeloneuropathy |
ALD AMN |
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. (7) 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, exophthalmus, blindness by approximately 6 months of age, and severe hematologic malfunction with bone marrow failure. (7) Seventy percent of these patients die before the age of 6, often of recurrent infections. (7) HSCT is the only curative therapy for this fatal disease.
Hematopoietic stem-cell transplantation for autoimmune disease, such as rheumatoid arthritis or multiple sclerosis, is considered separately in policy No. 8.01.25.
Policy
Allogeneic hematopoietic stem cell transplantation is considered medically necessary for selected patients with 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.
- Homozygous beta-thalassemia (i.e., thalassemia major)
Bone marrow failure syndromes
- Hereditary (including Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond, Diamond-Blackfan) or acquired (e.g., secondary to drug or toxin exposure) forms.
Primary immunodeficiencies
- Absent or defective T-cell function (e.g. severe combined immunodeficiency, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome)
- Absent or defective natural killer function (e.g. Chediak-Higashi syndrome)
- Absent or defective neutrophil function (e.g. Kostmann syndrome, chronic granulomatous disease, leukocyte adhesion defect)
(see policy guideline # 1)
Inherited metabolic disease
- Lysosomal and peroxisomal storage disorders except Hunter, Sanfilippo and Morquio syndromes
(see policy guideline # 2)
Genetic disorders affecting skeletal tissue
- Infantile malignant osteopetrosis (Albers-Schonberg disease or marble bone disease)
Policy Guidelines
1) The following lists the immunodeficiencies that have been successfully treated by allogeneic HSCT (4)
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 CD 45, CD3, CD8
DiGeorge syndrome
DNA ligase IV
Interleuken-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
Chediak-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
ICF syndrome
IPEX syndrome
NEMO deficiency
NF-κB inhibitor, alpha (IκB-alpha) deficiency
Nijmegen breakage syndrome
2) In the inherited metabolic disorders, allogeneic HSCT 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 HSCT 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 HSCT has not been effective in Hunter, Sanfilippo, or Morquio syndromes. (8)
Benefit Application
BlueCard/National Account Issues
No applicable information.
Rationale
Hemoglobinopathies
To date, over 1,600 patients worldwide have been treated for beta-thalassemia with allogeneic hematopoietic stem-cell transplant. (1) Overall survival rates have ranged from 65 –100% and thalassemia-free survival up to 73%. (1) The Pesaro risk stratification system classifies patients with thalassemia who are to undergo allogeneic HSCT into risk groups I through III on the presence of hepatomegaly, portal fibrosis, or adequacy of chelation (class I having no risk factors, II with 2 risk factors, and III with all 3). (9) The outcome of allogeneic HSCT in over 800 patients with thalassemia according to risk stratification has shown overall and event-free survival of 95% and 90% for Pesaro class I, 87% and 84% for class II, and 79% and 58% for class III. (9)
Most of the experience with allogeneic HSCT and sickle cell disease (SCD) comes from three major clinical series. (1) The largest series to date consisted of 87 symptomatic patients, the majority of whom received HLA-identical sibling donor allografts. The results from this series (10) and the other 2 (11, 12) were similar with overall survival rates ranging from 92 –94% and event-free survival from 82 –86% with a median follow-up ranging from 0.9 –17.9 years (1)
Experience with reduced-intensity preparative regimens and allogeneic HSCT for the hemoglobinopathies is limited to a small number of patients. Challenges with high rates of graft rejection (10 –30%) may be due to hemoglobinopathy patients possibly being allosensitized due to repeated blood transfusions and, as opposed to cancer patients who may undergo RIC allogeneic transplants, patients with hemoglobinopathies have received no prior immunosuppressive therapies and may even have significant bone marrow hyperplasia. (9)
Bone marrow failure syndromes
Fanconi anemia (FA)
In FA, bone marrow transplant is currently the only treatment that definitively restores normal hematopoiesis. Excellent results have been observed with the use of HLA-matched sibling allogeneic HSCT, with cure of the marrow failure and amelioration of the risk of leukemia. (2)
In a summary of allogeneic HSCT from matched related donors over the past 6 years in FA, totaling 103 patients, overall survival ranged from 83 –88% with transplant related mortality ranging from 8–18.5% and average chronic graft-versus-host disease (GVHD) of 12%. (13)
The outcomes in patients with FA and an unrelated donor allogeneic HSCT are not as promising. The European Group for Blood and Marrow Transplantation (EBMT) working party has analyzed the outcomes using alternative donors in 67 patients with FA. Median 2-year survival was 28 +/- 8%. (3) Causes of death included infection, hemorrhage, acute and chronic GVHD and liver veno-occlusive disease. (3) The Center for International Blood and Marrow Transplantation (CIBMTR) analyzed 98 patients transplanted with unrelated donor marrow between 1990 and 2003. Three year overall survival rates were 13% and 52% in patients who received non-fludarabine versus fludarabine-based regimens. (3)
Recently, fludarabine-containing reduced-intensity conditioning regimens have become more popular and used in FA. (13) In a recent report of 11 patients, overall survival was 82%, transplant-related mortality 9% and GVHD negligible. (14)
Other
Results with allogeneic HSCT in dyskeratosis congenita have been disappointing due to severe late effects, including diffuse vasculitis and lung fibrosis. (3) Currently, nonmyeloablative conditioning regimens with fludarabine are being explored; however, very few results are available at this time. (3)
Experience with allogeneic HSCT in Shwachman-Diamond syndrome is limited, as very few patients have undergone allogeneic transplants for this disease. (3)
In Diamond-Blackfan anemia, allogeneic HSCT is an option in corticosteroid-resistant disease. (3) In a report from the DBA registry, 20 of 354 registered patients underwent alloHSCT, and the 5-year survival rates were 87.5% if recipients received HLA-identical sibling grafts, but poor in recipients of alternative donors. (3) The CIBMTR reported the results in 61 patients who underwent HSCT between 1984 and 2000. (15) Sixty-seven percent of patients were transplanted with an HLA-identical sibling donor. Probability of overall survival after transplantation for patients transplanted from an HLA-identical sibling donor (versus an alternative donor) was 78% versus 45% [p =0.01] at 1 year and 76% versus 39% [p =0.01] at 3 years, respectively.
Primary immunodeficiencies (PID)
Currently, HSCT using HLA-identical sibling donors can provide correction of underlying PIDs such as SCID, Wiskott-Aldrich syndrome and other prematurely lethal X-linked immunodeficiencies in approximately 90% of cases. (16) According to a European series of 475 patients collected between 1968 and 1999, survival rates for SCID were approximately 80% with a matched sibling donor, 50% with a haploidentical donor, and 70% with a transplant from an unrelated donor. (16) Since 2000, overall survival for patients with SCID who have undergone HSCT is 71%. (4)
For Wiskott-Aldrich syndrome (WAS), an analysis of 170 patients transplanted between 1968-1996 demonstrated the impact of donor type on outcomes. (17) Fifty-five transplants were from HLA-identical sibling donors with a 5-year probability of survival of 87% (95% CI: 74 –93%), 48 from other relatives with a 5-year probability of survival of 52% (37 –65%), and 67 from unrelated donors with a 5-year probability of survival of 71% (58 –80%); p =0.0006.
For patients with genetic immune/inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH) the current results with allogeneic HSCT are 60 – 70% 5-year disease-free survival.
For patients with other immunodeficiencies, overall survival rates are 74%, with even better results (90%) with well-matched donors for defined conditions such as chronic granulomatous disease. (4)
Inherited metabolic diseases
In the past 25 years, hematopoietic stem cell transplants have been performed in about 20 of the approximately 40 known LSD and PSD. (6) The majority (> 80%) have been in patients with MPS I (Hurler syndrome), other MPS syndromes (MPS II, MPS III A and B, MPS VI), ALD, MLD and globoid leukodystrophy. (6) With the exception of Hurler and globoid cell leukodystrophy, most published data are single case reports or small series with short follow-up. (18) The benefit of allogeneic HSCT appears limited to select subsets of patients with few types of lysosomal storage diseases, and is not effective in patients who have developed overt neurological symptoms or in those with aggressive infantile forms. (18)
Impressive results have been observed with allogeneic HSCT in Hurler syndrome. The benefits that have been observed include improvement of neurocognitive functioning, joint integrity, motor development, linear growth, corneal clouding, cardiac function and others. (6) Survival of engrafted Hurler syndrome patients has been radically changed from that of untransplanted patients, with long-term survival data indicating that life-span will be extended many decades. (8) An analysis of nearly 150 transplanted patients with Hurler showed an overall survival rate of more than 80%. (19)
Experience with allogeneic HSCT and a reduced-intensity preparative regimen has been reported in 7 patients with Hurler syndrome. (20) Six of the patients received transplants from unrelated donors and one from a sibling. All patients had initial donor engraftment at 100 days, and there were no reports of severe acute graft versus host disease. Six of the 7 children were alive at a median of 1,014 days (range: 726–2,222 days) post-transplant.
The few patients with Maroteaux-Lamy and Sly syndrome that have been transplanted have shown promising results, with clinical improvement post-transplant. (8)
Outcomes with the leukodystrophies and allogeneic HSCT have been variable but somewhat promising. In boys and men with X-linked adrenoleukodystrophy (ALD), outcomes have depended on disease status at transplant and transplant-related complications (8), but reports of preservation of neuropsychologic and neurologic function have been made.
Fewer than 40 patients with Globoid-cell leukodystrophy (GLD) have undergone allogeneic HSCT; however, there have been reports of dramatic improvements in neurologic, neuropsychologic, and neurophysiologic function. (8)
Many patients with metachromatic leukodystrophy who have undergone allogeneic HSCT and had long-term engraftment have had amelioration of the disease signs and symptoms, and prolonged survival. (8)
Hunter syndrome is composed of two distinct clinical entities, a severe and an attenuated form. The attenuated form is characterized by a prolonged life span, minimal to no CNS involvement, and a slow progression. (8) Experience with allogeneic HSCT in patients with severe Hunter syndrome has shown that it has failed to alter the disease course favorably or significantly. (8) Some authors suggest that HSCT would not be justifiable in the attenuated form, because the risks outweigh the possible benefits. (8)
Experience with allogeneic HSCT in patients with MPS III (Sanfilippo syndrome) has also been disappointing with no alteration in the course of neuropsychologic deterioration seen in these patients. (8) The literature addressing the use of HSCT in Sanfilippo disease consists of 2 case reports. (21, 22) Vellodi and colleagues reported the outcomes of twin girls diagnosed with MPS III who underwent allogeneic HSCT and were followed for 9 years. (21) At the time of transplant, both girls were functioning in the low average range of intellectual development. Over the next 8 years, there was a steady decline in both girls’ cognitive development and both functioned in the area of significant developmental delay. The authors postulated that a possible reason for continued deterioration in the twins, despite the demonstration of full chimerism, was a very low level of enzyme throughout the years after transplant. One other patient with MPS III that has been transplanted was 5.3 years old at the time of transplant, and continued to regress after transplant. (22)
Clinical trials
A search of clinicaltrials.gov identified a nonrandomized, open label, uncontrolled, Phase II/III completed study of stem-cell transplantation for Hurler syndrome, Maroteaux-Lamy syndrome, Mannosidosis, or I-cell disease, to determine the safety and engraftment of donor hematopoietic cells using a certain conditioning regimen. Secondary outcome measures include survival. (NCT00176917)
An additional study for allogeneic-HSCT for high-risk inherited inborn errors using a reduced intensity conditioning regimen is currently recruiting patients. The estimated study completion date is September 2011 (NCT00383448).
Infantile Malignant Osteopetrosis
The success of allogeneic HSCT in infantile malignant osteopetrosis has depended greatly on the type of donor, with patients receiving grafts from HLA-identical siblings having a 5-year disease-free survival of 73 –79%, versus transplantation with an unrelated or mismatched donor 13 –45%. (7)
A retrospective analysis of 122 children who received an allogeneic HSCT for autosomal recessive osteopetrosis between 1980 and 2001 reported 5-year disease free survival of 73% for recipients of a genotype HLA-identical HSCT (n =40), 43% for those of a phenotype HLA-identical or one HLA-antigen mismatch graft from a related donor (n =21), 40% for recipients of a graft from a matched unrelated donor (n =20) and 24% for patients who received an HLA-haplotype-mismatch graft from a related donor (n =41). (23)
Physician Specialty Society and Academic Medical Center Input
In response to requests, input was received from 3 reviewers from one physician specialty society and 3 academic medical centers while this policy was under review for September 2009. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. There was general agreement with the policy statements. In particular, the reviewers were specifically asked to address the issue of the use of HSCT in the inherited metabolic diseases except for Hunter, Sanfilippo and Morquio syndromes; 4 reviewers agreed with the current policy statement, one disagreed and one did not address this specific question.
References:
- Bhatia M, Walters MC. Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future. Bone Marrow Transplant 2008; 41(2):109-17.
- Mehta P. Hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. (Chapter 17). In: Pediatric stem cell transplantation 2004. Jones and Bartlett Publishers; Sudbury, MA. pp. 281-316.
- Gluckman E, Wagner JE. Hematopoietic stem cell transplantation in childhood inherited bone marrow failure syndrome. Bone Marrow Transplant 2008; 41(2):127-32.
- Gennery AR, Cant AJ. Advances in hematopoietic stem cell transplantation for primary immunodeficiency. Immunol Allergy Clin North Am 2008; 28(2):439-56.
- Porta F, Forino C, De Martiis D et al. Stem cell transplantation for primary immunodeficiencies. Bone Marrow Transplant 2008; 41(suppl 2):S83-6.
- Prasad VK, Kurtzberg J. Emerging trends in transplantation of inherited metabolic diseases. Bone Marrow Transplant 2008; 41(2):99-108.
- Askmyr MK, Fasth A, Richter J. Towards a better understanding and new therapeutics of osteopetrosis. Br J Haematol 2008; 140(6):597-609.
- Mehta P. Metabolic diseases (Chapter 15). In: Pediatric stem cell transplantation 2004. Jones and Bartlett Publishers; Sudbury, MA. pp. 233-258.
- Mehta P. Hematopoietic stem cell transplantation for hemoglobinopathies (Chapter 16). In: Pediatric stem cell transplantation 2004. Jones and Bartlett Publishers; Sudbury, MA. pp. 259-79.
- Bernaudin F, Socie G, Kuentz M et al. Long-term results of related, myeloablative stem cell transplantation to cure sickle cell disease. Blood 2007; 110(7):2749-56.
- Walters MC, Patience M, Leisenring W et al. Bone marrow transplantation for sickle cell disease. N Engl J Med 1996; 335(6):369-76.
- Walters MC, Storb R, Patience M et al. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood 2000; 95(6):1918-24.
- Dufour C, Svahn J. Fanconi anaemia: new strategies. Bone Marrow Transplant 2008; 41(suppl 2):S90-5.
- Zanis-Neto J, Flowers ME, Medeiros CR et al. Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia. Br J Haematol 2005; 130(1):99-106.
- Roy V, Perez WS, Eapen M et al. Bone marrow transplantation for Diamond-Blackfan anemia. Biol Blood Marrow Transplant 2005; 11(8):600-8.
- Filipovich AH, Hematopoietic cell transplantation for correction of primary immunodeficiencies. Bone Marrow Transplant 2008; 42(suppl 1):S49-52.
- Filipovich AH, Stone J, Tomany SC et al. Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood 2001; 97(6):1598-603.
- Rovelli AM. The controversial and changing role of haematopoietic cell transplantation for lysosomal storage disorders: an update. Bone Marrow Transplant 2008; 41(suppl 2):S87-9.
- Boelens JJ, Wynn RF, O’Meara A et al. Outcomes of haematopoietic cell transplantation for MPS-1 in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant 2007; 40(3):225-33.
- Hansen MD, Filipovich AH, Davies SM et al. Allogeneic hematopoietic cell transplantation (HCT) in Hurler’s syndrome using a reduced intensity preparative regimen. Bone Marrow Transplant 2008; 41(4):349-53.
- Vellodi A, Young E, New M et al. Bone marrow transplantation for Sanfilippo disease type B. J Inherit Metab Dis 1992; 15(6):911-8.
- Bordigoni P, Vidailbet M, Lena M et al. Bone marrow transplantation for Sanfilippo syndrome. In Hobbs JR, ed. Correction of Certain Genetic Diseases by Transplantation. London: Cogent, 114-9.
- Driessen GJ, Gerritsen EJ, Fischer A et al. Long-term outcome of hematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report. Bone Marrow Transplant 2003; 32(7):657-63.
Codes |
Number |
Description |
| CPT | 38204 | Management of recipient hematopoietic cell donor search and cell acquisition |
| 38205 | Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, allogeneic | |
| 38208 | Thawing of previously frozen harvest | |
| 38209 | Washing of harvest | |
| 38210 | Specific cell depletion with harvest, T cell depletion | |
| 38212 | Red blood cell removal | |
| 38213 | Platelet depletion | |
| 38214 | Plasma (volume) depletion | |
| 38215 | Cell concentration in plasma, mononuclear, or buffy coat layer | |
| 38220 | Bone marrow, aspiration only | |
| 38221 | Biopsy, needle or trocar | |
| 38230 | Bone marrow harvesting for transplantation | |
| 38240 | Bone marrow or blood-derived peripheral stem-cell transplantation; allogeneic | |
| 38242 | Allogeneic donor lymphocyte infusions | |
| 86812, 86813, 86816, 86817, 86821, 86822 | Histocompatibility studies code range | |
| ICD-9 Procedure | 41.02 | Allogeneic bone marrow transplant with purging |
| 41.03 | Allogeneic bone marrow transplant without purging | |
| 41.05 | Allogeneic hematopoietic stem-cell transplant | |
| 41.08 | Allogeneic hematopoietic stem-cell transplant with purging | |
| 41.91 | Aspiration of bone marrow from donor for transplant | |
| 99.79 | Other therapeutic apheresis (includes harvest of stem cells) | |
| ICD-9 Diagnosis | 272.7 | Lipidoses (includes mucolipidosis) |
| 277.5 | Mucopolysaccharidosis | |
| 279.12 | Wiskott-Aldrich syndrome | |
| 279.2 | Combined immunity deficiency | |
| 282.41–282.49 | Thalassemia code range | |
| 284.0–284.9 | Aplastic anemia code range | |
| 288.01 | Congenital neutropenia (includes Kostmann’s syndrome) | |
| 756.52 | Osteopetrosis | |
| HCPCS | G0265 | Cryopreservation, freezing and storage of cells for therapeutic use, each cell line |
| G0266 | Thawing and expansion of frozen cells for therapeutic use, each cell line | |
| G0267 | Bone marrow or peripheral stem-cell harvest, modification or treatment to eliminate cell type(s) (e.g., T cells, metastatic carcinoma) | |
| Q0083, Q0084, Q0085 | Chemotherapy administration code range | |
| J9000, J9001, J9010, J9015, J9017, J9020, J9025, J9027, J9031, J9035, J9040, J9041, J9045, J9050, J9055, J9060, J9062, J9065, J9070, J9080, J9090, J9091, J9092, J9093, J9094, J9095, J9096, J9097, J9098, J9100, J9110, J9120, J9130, J9140, J9150, J9151, J9160, J9165, J9170, J9175, J9178, J9181, J9182, J9185, J9190, J9200, J9201, J9202, J9206, J9208, J9209, J9211, J9212, J9213, J9214, J9215, J9216, J9217, J9218, J9219, J9225, J9226, J9230, J9245, J9250, J9260, J9261, J9263, J9264, J9265, J9266, J9268, J9270, J9280, J9290, J9291, J9293, J9300, J9303, J9305, J9310, J9320, J9340, J9350, J9355, J9357, J9360, J9370, J9375, J9380, J9395, J9600, J9999 | Chemotherapy drug code range | |
| S2140 | Cord blood harvesting for transplantation, allogeneic | |
| S2142 | Cord blood-derived stem-cell transplantation, allogeneic | |
| S2150 | Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical, surgical, diagnostic and emergency services) | |
| Type of Service | Therapy | |
| Place of Service | Inpatient/Outpatient | |
Index
Aplastic Anemia, Stem Cell Transplant
High-dose Chemotherapy, Aplastic Anemia
High-dose Chemotherapy, Inborn Errors of Metabolism
High-dose Chemotherapy, Mucolipidoses
High-dose Chemotherapy, Mucopolysaccharidoses
High-dose Chemotherapy, Osteopetrosis
High-dose Chemotherapy, Severe Combined Immunodeficiencies
High-dose Chemotherapy, Sickle Cell Disease
High-dose Chemotherapy, Thalassemia
Inborn Errors of Metabolism, Stem Cell Transplant
Mucolipidoses, Stem Cell Transplant
Mucopolysaccharidoses, Stem Cell Transplant
Osteopetrosis, Stem Cell Transplant
Positron emission tomography
Severe Combined Immunodeficiencies (SCID), Stem Cell Transplant
Sickle Cell Disease, Stem Cell
Thalassemia, Stem Cell Transplant
Policy History
| Date | Action | Reason |
| 12/01/99 | Add to Therapy section | New policy Policy represents revision of original policy No. 7.03.10. Discussion of myelofibrosis, originally included in this policy, is now addressed in policy No. 8.01.21. Policy statement on remaining indications is unchanged |
| 7/12/02 | Replace policy | Policy reviewed without literature review; new review date only |
| 12/18/02 | Replace policy | Update CPT codes only |
| 4/16/04 | Replace policy | Policy updated with literature search; no change in policy statement. |
| 4/1/05 | Replace policy | Policy updated with literature search; no change in policy statement; no further review scheduled |
| 12/12/06 | Replace policy | Policy updated with literature search for March 2005 through October 2006; no change in policy statement. Policy update changed to annual review with literature search |
| 12/13/07 | Replace policy | Policy updated with literature search; no change in policy statement. |
| 09/10/09 | Replace policy | Policy updated and extensively edited based on literature search. Except for one change, the intent of the policy statements is unchanged. The change in the policy statement is that treatment of Hunter, Sanfilippo, and Morquio syndromes are not included in the list of lysosomal and peroxisomal storage diseases where allo-HSCT may be considered medically necessary. Clinical input reviewed; references 21 and 22 added. |
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