0627 hematopoietic cell transplantation for aplastic anemia ......2018/09/06 · allogeneic bone...
TRANSCRIPT
Page 1 of 16
(https://www.aetna.com/)
Hematopoietic CellTransplantation for AplasticAnemia and other Bone Marrow Failure Syndromes
Clinical Policy Bulletins Medical Clinical Policy Bulletins
Policy History
Last
Review
09/06/2018
Effective: 06/28/200
Next Review:
06/27/2019
Review History
Definitions
Number: 0627
Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.
Aetna considers allogeneic hematopoietic cell transplantation medically necessary
for the treatment of severe aplastic anemia, Diamond-Blackfan anemia, Fanconi's
anemia, paroxysmal nocturnal hemoglobinuria, and pure red cell aplasia when
members meet the transplanting institution's selection criteria.
In the absence of a institution's selection criteria, Aetna considers allogeneic
hematopoietic cell transplantation medically necessary for the treatment of severe
aplastic anemia when the member has at least 3 of the 4 following features:
Bone marrow cellularity less than 25 % (markedly hypocellular)
Neutrophil count less than 0.5 x 109/L
Reticulocyte count less than 1 % or less than 20 x 109/L (corrected for
hematocrit)
Untransfused platelet count less than 20 x 109/L
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 2 of 16
In the absence of a institution's selection criteria, Aetna considers allogeneic
hematopoietic cell transplantation medically necessary for the treatment of pure red
cell aplasia when the member has the following features.
Bone marrow cellularity less than 25 % (markedly hypocellular); and
Reticulocyte count less than 1 % or less than 20 x 109/L (corrected for
hematocrit).
In the absence of an institution's selection criteria, Aetna considers allogeneic
hematopoietic cell transplantation medically necessary for the treatment of
Diamond-Blackfan anemia in persons who are refractory to corticosteroids.
In the absence of an institution's selection criteria, Aetna considers allogeneic
hematopoietic cell transplantation medically necessary for Fanconi's anemia in
persons with severe bone marrow failure, myelodysplastic syndrome, or acute
myelogenous leukemia.
In the absence of an institution's selection criteria, Aetna considers
allogeneic hematopoietic cell transplantation medically necessary in persons with
paroxysmal nocturnal hemoglobinuria with ongoing transfusion requirements and a
suitable HLA-matched donor.
Aetna considers repeat allogeneic stem cell transplantation medically necessary for
primary graft failure, failure to engraft or rejection in severe aplastic anemia,
Diamond-Blackfan anemia, Fanconi's anemia, paroxysmal nocturnal
hemoglobinuria, and pure red cell aplasia.
Aetna considers autologous hematopoietic cell transplantation experimental and
investigational for the treatment of severe aplastic anemia, Diamond-Blackfan
anemia, Fanconi's anemia, paroxysmal nocturnal hemoglobinuria, and pure red cell
aplasia because its effectiveness for these indications has not been established.
Background
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
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 3 of 16
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 3 of 4 of these symptoms are present, the
median survival without therapy is about 3 months, with only 20 % of patients
surviving for 12 months. Currently, 2 definitive treatments are available for patients
with severe AA: (i) immuno-suppressive therapy (IST) that includes the use of
anti-thymocyte globulin, cyclosporine, and c yclophosphamide; 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.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 4 of 16
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).
Bone marrow failure (BMF) syndromes entail a broad group of diseases of varying
etiologies, in which hematopoeisis is abnormal or completely arrested in one or
more cell lines. Bone marrow failure syndromes can be an acquired AA or can be
congenital, as part of such syndromes as Fanconi anemia (FA), Diamond Blackfan
anemia (DBA), and Schwachman Diamond syndrome. Hematopoietic bone
marrow/stem cell transplantation is a therapeutic option for patients with BMF
syndromes (Steele et al, 2006, Myers and Davies, 2009, Mehta et al, 2010).
In a report from the Aplastic Anemia Committee of the Japanese Society of
Pediatric Hematology on hematopoietic stem cell transplantation (HSCT) for DBA,
Mugishima et al (2007) stated that transfusion-dependent DBA patients opt for
allogeneic HSCT as curative therapy. These investigators analyzed clinical
outcomes of 19 transplanted Japanese patients. Prior to HSCT, 10 patients (53 %)
suffered hemosiderosis with organ dysfunction, and all 8 with short stature (42 %)
had adverse effects of prednisolone. Median age at the time of HSCT was 56
months. Transplantation sources were 13 bone marrow (6 HLA-matched siblings,
and 6 HLA-matched and 1 HLA-mismatched unrelated donors), 5 cord blood (2
Page 5 of 16
HLA-matched siblings and 3 HLA-mismatched unrelated donors), and 1 peripheral
blood from haploidentical mother. All 13 patients with BMT and 2 with sibling cord
blood transplantation (CBT) had successful engraftment. Of 3 patients who
underwent unrelated CBT, 1 died after engraftment, and the other 2 had graft
failure but succeeded in a second BMT from an HLA-disparate father and unrelated
donor, respectively. One died shortly after haploidentical PBSCT. The 5-year failure-
free survival rate after BMT was higher than CBT (100 %: 40 %, p = 0.002). Platelet
recovery was slower in 7 unrelated BMT than in 6 sibling BMT (p = 0.030). No other
factors were associated with engraftment and survival. These results suggested that
allogeneic BMT, but not unrelated CBT, is an effective HSCT for refractory DBA.
In a report from the Italian pediatric group, Locatelli and colleagues (2007) noted
that HSCT represents the only treatment potentially able to prevent/rescue the
development of marrow failure and myeloid malignancies in patients with FA. While
in the past HSCT from an HLA-identical sibling was proven to cure many patients, a
higher incidence of treatment failure has been reported in recipients of an unrelated
donor (UD) or HLA-partially matched related allograft. These researchers
analyzed the outcome of 64 FA patients (age range of 2 to 20 years) who
underwent HSCT between January 1989 and December 2005. Patients were
transplanted from either an HLA-identical sibling (n = 31), an UD (n = 26), or an
HLA-partially matched relative (n = 7). T-cell depletion of the graft was performed
in patients transplanted from an HLA-disparate relative. The 8-year estimate of
overall survival (OS) for the whole cohort was 67 %; it was 87 %, 40 % and 69 %
when the donor was an HLA-identical sibling, an UD, and a mis-matched relative,
respectively (p < 0.01). The outcome of recipients of grafts from an UD improved
over time, the probability of survival being 10 % and 72 % for patients transplanted
before and after 1998, respectively (p < 0.05). The OS probability of children who
did or did not receive fludarabine in preparation for the allograft was 86 % and 59
%, respectively (p < 0.05). These data provided support to the concept that a
relevant proportion of FA patients undergoing HSCT can now be successfully
cured, even in the absence of an HLA-identical sibling, especially if the conditioning
regimen includes fludarabine.
Roth and colleagues (2009) stated that paroxysmal nocturnal hemoglobinuria
(PNH) is characterized by the clinical triad of corpuscular hemolytic anemia,
thrombophilia, and cytopenia. This is caused by an acquired mutation of the PIG
(phosphatidylinositol glycan)-A gene of the pluripotent hematopoetic stem cell. This
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 6 of 16
results in a deficiency of GPI (glycosylphosphatidylinositol)-anchors and GPI-
anchored proteins on the surface of affected blood cells. Flow cytometry is the
standard for diagnosis and measurement of type and size of the PNH clone.
Treatment of PNH is mainly symptomatic. Allogeneic BMT is the only curative
option in case of severe complications during the course of the diseases.
Li and colleagues (2013) noted that although high-dose cyclophosphamide seems
to achieve durable complete remission, there are still concerns about its too much
early toxicity. Thus, these researchers designed a clinical study to examine the
effects of high-dose cyclophosphamide/anti-thymocyte globulin (ATG) combined
with cord blood infusion as first-line therapy for patients with severe AA. Between
January 2003 and September 2007, these investigators treated 16 treatment-naive
patients with severe AA with cord blood infusion after high-dose cyclophosphamide
(50 mg/kg/day × 2) and rabbit ATG (3 mg/kg/day × 5) therapy. Although only 1
patient had durable full donor engraftment, 14 of the enrolled 16 patients had rapid
autologous hematopoietic recovery. The median recovery time for neutrophils and
platelets was only 23 and 37 days after infusion of cord blood. Of the 15
responding patients, all patients achieved treatment-free remission: 9 patients met
the criteria for a complete remission; 6 patients achieved a partial remission. The
authors concluded that infusion of cord blood after high-dose
cyclophosphamide/ATG resulted in a rapid autologous hematologic recovery and a
high response rate in patients with treatment-naive patients with severe AA. They
stated that these promising results merit further investigation and confirmation on a
larger number of patients.
An UpToDate review on “Aplastic anemia: Prognosis and treatment” (Schrier, 2013)
states that “Only a fraction of patients with severe aplastic anemia in first or second
complete remission are able to mobilize sufficient stem cells to undergo autologous
hematopoietic cell transplantation (HCT). Accordingly, patients with relapsing or
resistant disease, who have even fewer mobilizable stem cells than those in
remission, are not candidates for autologous HCT". Furthermore, an UpToDate
review on “Hematopoietic cell transplantation in aplastic anemia” (Negrin, 2013)
recommends the use of allogeneic HCT; it does not mention the use of autologous
HCT as a therapeutic option.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 7 of 16
UpToDate reviews on “Hematopoietic cell transplantation for Diamond-Blackfan
anemia and the myelodysplastic syndromes in children” (Khan, 2013) and
“Hematopoietic cell transplantation for idiopathic severe aplastic anemia and
Fanconi anemia in children” (Khan and Negrin, 2013) do not mention the use of
autologous HCT as a therapeutic option.
An UpToDate review on “Diagnosis and treatment of paroxysmal nocturnal
hemoglobinuria” (Rosse, 2013) states that “autologous transplantation is unlikely to
be successful because of the difficulty in obtaining sufficient numbers of normal
stem cells”.
In a Cochrane review, Peinemann and associates (2013) evaluated the
effectiveness and adverse events of first-line allogeneic HSCT of HLA-matched
sibling donors compared to first-line immunosuppressive therapy including
cyclosporine and/or anti-thymocyte or anti-lymphocyte globulin in patients with
acquired severe AA. The authors concluded that there are insufficient and biased
data that do not allow any conclusions to be made about the comparative
effectiveness of first-line allogeneic HSCT of an HLA-matched sibling donor and
first-line treatment with cyclosporine and/or anti-thymocyte or anti-lymphocyte
globulin (as first-line immunosuppressive therapy). These investigators stated that
they were unable to make firm recommendations regarding the choice of
intervention for treatment of acquired severe AA.
Williams and colleagues (2014) noted that randomized clinical trials in pediatric AA
are rare and data to guide standards of care are scarce. Eighteen pediatric
institutions formed the North American Pediatric Aplastic Anemia Consortium
(NAPAAC) to foster collaborative studies in AA. The initial goal of NAPAAC was to
survey the diagnostic studies and therapies utilized in AA. The survey indicated
considerable variability among institutions in the diagnosis and treatment of AA.
There were areas of general consensus, including the need for a bone marrow
evaluation, cytogenetic and specific fluorescent in-situ hybridization assays to
establish diagnosis and exclude genetic etiologies with many institutions requiring
results prior to initiation of IST; uniform referral for HSCT as first line therapy if an
HLA-identical sibling is identified; the use of first-line IST containing horse anti
thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not
identified; supportive care measures; and slow taper of CSA after response. Areas
of controversy included the need for telomere length results prior to IST, the time
after IST initiation defining a treatment failure; use of hematopoietic growth factors;
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 8 of 16
the preferred rescue therapy after failure of IST; the use of specific hemoglobin and
platelet levels as triggers for transfusion support; the use of prophylactic antibiotics;
and follow-up monitoring after completion of treatment. The authors concluded that
these initial survey results reflected heterogeneity in diagnosis and care amongst
pediatric centers and emphasized the need to develop evidence-based diagnosis
and treatment approaches in this rare disease.
Aplastic anemia is a disorder characterized by the presence of pancytopenia and a
hypo-cellular bone marrow. Acquired pure red cell aplasia (PRCA), a part of a
unique form of AA, is a rare condition of profound anemia characterized by the
absence of reticulocytes and the virtual absence of erythroid precursors in the bone
marrow.
An UpToDate review on “Determining eligibility for allogeneic hematopoietic cell
transplantation” (Deeg and Sandmaier, 2014) states that “In general, allo-HCT may
be considered in the following settings …. Nonmalignant inherited and acquired
marrow disorders -- Treatment of sickle cell anemia, beta-thalassemia major,
refractory Diamond-Blackfan anemia, myelodysplastic syndrome, idiopathic severe
aplastic anemia, paroxysmal nocturnal hemoglobinuria, pure red cell aplasia,
Fanconi anemia, amegakaryocytosis, or congenital thrombocytopenia”.
Second Hematopoietic Stem Cell Transplantation for Graft Failure in Adult Patients with Severe Aplastic Anemia
Yahng and colleagues (2018) stated that data regarding the optimal approach for
2nd allogeneic HSCT (allo-HSCT) after graft failure (GF) in acquired severe AA
(SAA) are still limited and heterogeneous. These researchers examined 24
patients who underwent 2nd HLA-matched sibling donor (MSD) peripheral blood
HSCT for GF. The re-conditioning regimen (TNI-750/ATG) consisted of a single-
dose of total nodal irradiation (TNI, 750 cGy) and anti-thymocyte globulin (ATG;
Thymoglobulin, 1.25 mg/kg/day for 3 days). All but 1 patient achieved successful
engraftment of neutrophils (median of 12 days, range of 5 to 21) and platelets
(median of 15 days, range of 9 to 316); 2 patients with subsequent secondary GF
achieved successful engraftment after a 3rd HSCT from the same MSD. After a
median follow-up of 57.4 months (range of 11.2 to 155.2), the 5-year OS and
failure-free survival were 95.7 % (95 % confidence interval [CI]: 87.7 % to 100 %)
and 87.5 % (95 % CI: 75.2 % to 100 %), respectively; 1 patient developed grade II
acute GVHD, and the 2-year cumulative incidence of chronic GVHD was 23.5 %
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 9 of 16
(95 % CI: 8.1 % to 43.5 %). The authors concluded that the findings of this study
demonstrated successful outcomes following a 2nd MSD HSCT in SAA after GF,
and the results suggested TNI-750/ATG is a feasible re-conditioning option.
CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added f or clarification purposes. Codes requiring a 7th character are represented by "+":
Transplantation - Allogeneic:
CPT codes covered if selection criteria are met:
38230 Bone marrow harvesting for transplantation; allogeneic
38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per
donor
86813 HLA typing; A, B or C multiple antigens
86817 DR/DQ, multiple antigens
86821 lymphocyte culture, mixed (MCL)
86822 lymphocyte culture, primed (PLC)
Other CPT codes related to the CPB:
38204 - 38215 Bone marrow or stem cell services/procedures
85004 - 85049 Blood count
85055 Reticulated platelet assay
85060 Blood smear, peripheral, interpretation by physician with written report
85097 Bone marrow, smear interpretation
86920 - 86923 Compatibility test each unit
HCPCS codes covered if selection criteria are met:
ICD-10 codes covered if selection criteria are met:
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 10 of 16
D59.5
D60.0 - D61.9
T86.5
Z94.84
Transplantation - Autologous:
CPT codes not covered for indications listed in the CPB:
The above policy is based on the following references:
1. Fonseca R, Tefferi A. Practical aspects in the diagnosis and management of
aplastic anemia. Am J Med Sci. 1997;313(3):159-169.
2. Storb R. Aplastic anemia. J Intraven Nurs. 1997;20(6):317-322.
3. Guinan EC. Clinical aspects of aplastic anemia. Hematol Oncol Clin North
Am. 1997;11(6):1025-1044.
4. Horowitz MM. Current status of allogeneic bone marrow transplantation
in acquired aplastic anemia. Semin Hematol. 2000;37(1):30-42.
5. Bacigalupo A, Brand R, Oneto R, et al. Treatment of acquired severe
aplastic anemia: Bone marrow transplantation compared with
immunosuppressive therapy -- The European Group for Blood and
Marrow Transplantation experience. Semin Hematol. 2000;37(1):69-80.
6. Socie G, Gluckman E. Cure from severe aplastic anemia in vivo and late
effects. Acta Haematol. 2000;103(1):49-54 .
7. Killick SB, Marsh JC. Aplastic anaemia: Management. Blood Rev. 2000;14
(3):157-171.
8. Kojima S, Horibe K, Inaba J, et al. Long-term outcome of acquired aplastic
anaemia in children: Comparison between immunosuppressive therapy
and bone marrow transplantation. Br J Haematol. 2000a;111(1):321-328.
9. Kojima S, Nakao S, Tomonaga M, et al. Consensus Conference on the
Treatment of Aplastic Anemia. Int J Hematol. 2000b;72(1):118-123.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 11 of 16
10. Linker CA. Anemias. In: Current Medical Diagnosis & Treatment 2001. 40th
Ed, LM Tierney Jr, et al. eds. New York, NY: Lange Medical Books/McGraw-
Hill; 2001; Ch. 13:505-558.
11. Young NS. Acquired aplastic anemia. Ann Intern Med. 2002;136(7):534
546.
12. Abdelkefi A, Ben Othman T, Ladeb S, et al. Bone marrow transplantation
for patients with acquired severe aplastic anemia using cyclophosphamide
and antithymocyte globulin: The experience from a single center. Hematol
J. 2003;4(3):208-213.
13. Kim HJ, Park CY, Park YH, et al. Successful allogeneic hematopoietic stem
cell transplantation using triple agent immunosuppression in severe
aplastic anemia patients. Bone Marrow Transplant. 2003;31(2):79-86.
14. Geissler K. Pathophysiology and treatment of aplastic anemia. Wien Klin
Wochenschr. 2003;115(13-14):444-450.
15. Brodsky RA, Jones RJ. Aplastic anaemia. Lancet. 2005;365(9471):1647
1656.
16. Rzepecki P, Sarosiek T, Szczylik C. Alemtuzumab, fludarabine and
melphalan as a conditioning therapy in severe aplastic anemia and
hypoplastic myelodysplastic syndrome--single center experience. Jpn J Clin
Oncol. 2006 ;36(1):46-49.
17. Young NS, Calado RT, Scheinberg P. Current concepts in the
pathophysiology and treatment of aplastic anemia. Blood. 2006;108
(8):2509-2519.
18. Champlin RE, Perez WS, Passweg JR, et al. Bone marrow transplantation
for severe aplastic anemia: A randomized controlled study of conditioning
regimens. Blood. 2007;109(10):4582-4585.
19. Institut fuer Qualitaet und Wirtschaftlichkeit im Gesundheitswesen
(IQWiG). Stem cell transplantation in acquired severe aplastic anaemia.
Summary. Report N05-03B.Cologne, Germany: IQWiG; 2007.
20. Perez-Albuerne ED, Eapen M, Klein J, et al. Outcome of unrelated donor
stem cell transplantation for children with severe aplastic anemia. Br J
Haematol. 2008;141(2):216-223.
21. Young NS, Scheinberg P, Calado RT. Aplastic anemia. Curr Opin Hematol.
2008;15(3):162-168.
22. Bacigalupo A. Treatment strategies for patients with severe aplastic
anemia. Bone Marrow Transplant. 2008;42 Suppl 1:S42-S44.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 12 of 16
23. Yoshimi A, Kojima S, Taniguchi S, et al. Unrelated cord blood
transplantation for severe aplastic anemia. Biol Blood Marrow Transplant.
2008;14(9):1057-1063.
24. Chan KW, McDonald L, Lim D, et al. Unrelated cord blood transplantation
in children with idiopathic severe aplastic anemia. Bone Marrow
Transplant. 2008;42(9):589-595.
25. Ohga S, Mugishima H, Ohara A, et al; Aplastic Anemia Committee Japanese
Society of Pediatric Hematology. Diamond-Blackfan anemia in Japan:
Clinical outcomes of prednisolone therapy and hematopoietic stem cell
transplantation. Int J Hematol. 2004;79(1):22-30.
26. Guardiola P, Socie G, Li X, et al. Acute graft-versus-host disease in patients
with Fanconi anemia or acquired aplastic anemia undergoing bone
marrow transplantation from HLA-identical sibling donors: Risk factors
and influence on outcome. Blood. 2004;103(1):73-77.
27. Steele JM, Sung L, Klaassen R, et al; Canadian Inherited Marrow Failure
Registry. Disease progression in recently diagnosed patients with inherited
marrow failure syndromes: A Canadian Inherited Marrow Failure Registry
(CIMFR) report. Pediatr Blood Cancer. 2006;47(7):918-925.
28. Bitan M, Or R, Shapira MY, et al. Fludarabine-based reduced intensity
conditioning for stem cell transplantation of Fanconi anemia patients from
fully matched related and unrelated donors. Biol Blood Marrow
Transplant. 2006;12(7):712-718.
29. Tan PL. Wagner JE, Auerbach AD, et al. Successful engraftment without
radiation after fludarabine-based regimen in Fanconi anemia patients
undergoing genotypically identical donor hematopoietic cell
transplantation. Pediatr Blood Cancer. 2006;46(5):630-636.
30. Mugishima H, Ohga S, Ohara A, et al; for the Aplastic Anemia Committee of
the Japanese Society of Pediatric Hematology. Hematopoietic stem cell
transplantation for Diamond-Blackfan anemia: A report from the Aplastic
Anemia Committee of the Japanese Society of Pediatric Hematology.
Pediatr Transplant. 2007;11(6):601-6077.
31. Locatelli F, Zecca M, Pession A, et al; Italian pediatric group. The outcome
of children with Fanconi anemia given hematopoietic stem cell
transplantation and the influence of fludarabine in the conditioning
regimen: A report from the Italian pediatric group. Haematologica.
2007;92(10):1381-1388.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 13 of 16
32. Chaudhury S, Auerbach AD, Kernan NA, et al. Fludarabine-based
cytoreductive regimen and T-cell-depleted grafts from alternative donors
for the treatment of high-risk patients with Fanconi anaemia. Br J
Haematol. 2008;140(6):644-655.
33. Maury S, Bacigalupo A, Anderlini P, et al; Severe Aplastic Anemia Working
Party, European Group for Blood and Marrow Transplantation (EBMT
SAAWP). Improved outcome of patients older than 30 years receiving HLA-
identical sibling hematopoietic stem cell transplantation for severe
acquired aplastic anemia using fludarabine-based conditioning: A
comparison with conventional conditioning regimen. Haematologica.
2009;94(9):1312-1315.
34. Peinemann F, Grouven U, Kröger N, et al. Unrelated donor stem cell
transplantation in acquired severe aplastic anemia: A systematic review.
Haematologica. 2009;94(12):1732-1742.
35. Marsh JC, Ball SE, Cavenagh J, et al; British Committee for Standards in
Haematology. Guidelines for the diagnosis and management of aplastic
anaemia. Br J Haematol. 2009;147(1):43-70.
36. Green AM, Kupfer GM. Fanconi anemia. Hematol Oncol Clin North Am.
2009;23(2):193-214.
37. Röth A, Dührsen U, Schrezenmeier H, Schubert J. Paroxysmal nocturnal
hemoglobinuria (PNH). Pathogenesis, diagnosis and treatment. Dtsch Med
Wochenschr. 2009;134(9):404-409.
38. Matos-Fernandez NA, Abou Mourad YR, Caceres W, Kharfan-Dabaja MA.
Current status of allogeneic hematopoietic stem cell transplantation for
paroxysmal nocturnal hemoglobinuria. Biol Blood Marrow Transplant.
2009;15(6):656-661.
39. MacMillan ML, Wagner JE. Haematopoeitic cell transplantation for Fanconi
anaemia -- when and how? Br J Haematol. 2010;149(1):14-21.
40. Myers KC, Davies SM. Hematopoietic stem cell transplantation for bone
marrow failure syndromes in children. Biol Blood Marrow Transplant.
2009;15(3):279-292.
41. Lipton JM, Ellis SR. Diamond-Blackfan anemia: Diagnosis, treatment, and
molecular pathogenesis. Hematol Oncol Clin North Am. 2009;23(2):261
282.
42. Leblanc T. Blackfan-Diamond disease. Orphanet. Paris, France:
Orphanet/INSERM; February 2009.
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 14 of 16
43. Mehta P, Locatelli F, Stary J, Smith FO. Bone marrow transplantation for
inherited bone marrow failure syndromes. Pediatr Clin North Am. 2010;57
(1):147-170.
44. Alter BP, Giri N, Savage SA, et al. Malignancies and survival patterns in the
National Cancer Institute inherited bone marrow failure syndromes cohort
study. Br J Haematol. 2010;150(2):179-188.
45. Bizzetto R, Bonfim C, Rocha V, et al; Eurocord and SAA-WP from EBMT.
Outcomes after related and unrelated umbilical cord blood
transplantation for hereditary bone marrow failure syndromes other than
Fanconi anemia. Haematologica. 2011;96(1):134-141.
46. Peinemann F, Grouven U, Kroger N, et al. First-line matched related donor
hematopoietic stem cell transplantation compared to immunosuppressive
therapy in acquired severe aplastic anemia. PLoS One. 2011;6(4):e18572.
47. Li Y, Sheng Z, Niu S, et al. Rapid and complete reconstitution of autologous
haemopoiesis after cord blood infusion in treatment-naive patients with
severe aplastic anemia receiving high-dose cyclophosphamide/ATG
therapy. Eur J Haematol. 2013;90(1):45-50.
48. Schrier SL. Aplastic anemia: Prognosis and treatment. UpToDate [online
serial]. Waltham, MA: UpToDate; reviewed May 2013.
49. Negrin RS. Hematopoietic cell transplantation in aplastic anemia.
UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2013.
50. Khan S. Hematopoietic cell transplantation for Diamond-Blackfan anemia
and the myelodysplastic syndromes in children. UpToDate [online serial].
Waltham, MA: UpToDate; reviewed May 2013.
51. Khan S, Negrin RS. Hematopoietic cell transplantation for idiopathic severe
aplastic anemia and Fanconi anemia in children. UpToDate [online serial].
Waltham, MA: UpToDate; reviewed May 2013.
52. Rosse WF. Diagnosis and treatment of paroxysmal nocturnal
hemoglobinuria. UpToDate [online serial]. Waltham, MA:
UpToDate; reviewed May 2013.
53. Peinemann F, Bartel C, Grouven U. First-line allogeneic hematopoietic
stem cell transplantation of HLA-matched sibling donors compared with
first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for
acquired severe aplastic anemia. Cochrane Database Syst Rev.
2013;7:CD006407.
54. Williams DA, Bennett C, Bertuch A, et al. Diagnosis and treatment of
pediatric acquired aplastic anemia (AAA): An initial survey of the North
Proprietary
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019
Page 15 of 16
American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatr Blood
Cancer. 2014;61(5):869-874.
55. Deeg HJ, Sandmaier BM. Determining eligibility for allogeneic
hematopoietic cell transplantation. UpToDate [online serial]. Waltham,
MA: UpToDate; reviewed April, 2014.
56. Barone A, Lucarelli A, Onofrillo D, et al. Diagnosis and management of
acquired aplastic anemia in childhood. Guidelines from the Marrow
Failure Study Group of the Pediatric Haemato-Oncology Italian Association
(AIEOP). Blood Cells Mol Dis. 2015;55(1):40-47.
57. Inamoto Y, Flowers ME, Wang T, et al. Tacrolimus versus cyclosporine after
hematopoietic cell transplantation for acquired aplastic anemia. Biol Blood
Marrow Transplant. 2015;21(10):1776-1782.
58. Xiao PF, Hu SY, He HL, et al. Efficacy analysis of allogeneic hematopoietic
stem cell transplantation for children with severe aplastic anemia.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23(4):1103-1107.
59. Yahng SA, Park SS, Jeon YW, et al. Successful outcomes of second
hematopoietic stem cell transplantation with total nodal irradiation and
ATG conditioning for graft failure in adult patients with severe aplastic
anemia. Bone Marrow Transplant. 2018 Mar 21 [Epub ahead of print].
60. Li Y, Duan F, Xiao H, et al. Therapeutic outcomes of haploidentical
allogeneic hematopoietic stem cell transplantation in patients with severe
aplastic anemia: A multicenter study. Transplantation. 2018 Apr 19 [Epub
ahead of print].
Page 16 of 16
Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan
benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial,
general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care
services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in
private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible
for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to
change.
Copyright © 2001-2019 Aetna Inc.
http://www.aetna.com/cpb/medical/data/600_699/0627.html 09/24/2019 Proprietary
AETNA BETTER HEALTH® OF PENNSYLVANIA
Amendment to Aetna Clinical Policy Bulletin Number: 0627 Hematopoietic
Cell Transplantation for Aplastic Anemia and other Bone Marrow Failure Syndromes
There are no amendments for Medicaid.
www.aetnabetterhealth.com/pennsylvania annual 10/01/2019