| Transplant Section - Pancreas Transplant
| Topic: Pancreas Transplant |
Date
of Origin: 01/1996 |
Section: Transplant
|
Policy No: 6 |
| Effective Date: 01/01/2012 |
|
| |
IMPORTANT REMINDER
Regence Medical Policies are developed to provide guidance for members and providers regarding
coverage in accordance with contract terms. Benefit determinations are based in all cases on
the applicable contract language. To the extent there may be any conflict between the Medical
Policy and contract language, the contract language takes precedence.
PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that
are considered investigational or cosmetic. Providers may bill members for services or
procedures that are considered investigational or cosmetic. Providers are encouraged to inform
members before rendering such services that the members are likely to be financially responsible
for the cost of these services.
DESCRIPTION
Transplantation of a normal pancreas is a treatment
method for patients with diabetes mellitus. Pancreas
transplantation can restore glucose control, and is
intended to prevent, halt, or reverse the secondary
complications of insulin dependent Type 1 diabetes
mellitus (IDDM). Achievement of insulin independence
with resultant decreased morbidity and increased quality
of life is the primary health outcome of pancreas transplantation.
While pancreas transplantation is generally not considered
a life-saving treatment, in a small subset of patients
who experience life-threatening complications from
IDDM, pancreas transplantation could be considered
life-saving. In addition to the immune rejection issues
common to all allograft transplants, autoimmune destruction
of beta cells has been observed in the transplanted
pancreas, presumably from the same mechanism responsible
for type 1 diabetes.[1]
Pancreas transplantation occurs in several different
scenarios such as:
| 1. |
Type 1 diabetic patient with renal
failure who may receive a cadaveric simultaneous
pancreas/kidney transplant (SPK) |
| 2. |
Type 1 diabetic patient who may receive a cadaveric
or living-related pancreas transplant after a kidney
transplantation (pancreas after kidney, i.e., PAK) |
| 3. |
Non-uremic type 1 diabetic patient with specific
severely disabling and potentially life-threatening
diabetic problems who may receive a pancreas transplant
alone (PTA). |
Pancreas transplant alone (PTA) has also been investigated
in patients following total pancreatectomy for chronic
pancreatitis. The experience with SPK transplants is
more extensive than that of other transplant options.
The 5-year patient survival and graft survival is
as follows [2]:
| • |
SPK: 87%; graft survival
is 78% for the kidney and 72% for the pancreas |
| • |
PTA: Patient survival 89%;
graft survival 52% |
| • |
PAK: Similar to PTA |
The approach to retransplantation varies according
to the cause of failure. Surgical/technical complications
such as venous thrombosis are the leading cause of
pancreatic graft loss among diabetic patients. Graft
loss from chronic rejection may result in sensitization,
increasing both the difficulty of finding a cross-matched
donor and the risk of rejection of a subsequent transplant.
Each center has its own guidelines based on experience;
some transplant centers may wait to allow reconstitution
of the immune system before initiating retransplant
with an augmented immunosuppression protocol.
Note: Islet cell transplantation
is considered separately in TRG Medical Policy, Transplant,
No. 13.
POLICY/CRITERIA
| I. |
Candidates
for all types of pancreas transplant must meet
all of the following criteria: |
| |
A. |
Adequate
cardiopulmonary status |
| |
B. |
Absence
of all of the following: |
| |
|
1. |
Untreated
systemic infection making immunosuppression unsafe,
including chronic infection |
| |
|
2. |
Known current malignancy,
including but not limited to metastatic cancer |
| |
|
3. |
Recent malignancy with
high risk of recurrence |
| |
|
4. |
Other irreversible
end-stage disease not attributed to kidney or pancreatic
disease |
| |
C. |
Documentation
of patient compliance with medical management |
| II. |
The following
may be considered medically necessary if
all of the above criteria are met: |
| |
A. |
A combined
pancreas-kidney transplant in diabetic patients
with uremia. |
| |
B. |
Pancreas
transplant after a prior kidney transplant in patients
with IDDM. |
| |
C. |
Pancreas
transplant alone in patients with documentation
of one or both of the following conditions, which
persist in spite of optimal medical management: |
| |
|
1. |
Severely disabling
and potentially life-threatening hypoglycemia unawareness
as evidenced by chart notes or emergency room visits;
OR |
| |
|
2. |
Potentially life-threatening
labile diabetes as evidenced by documentation of
erratic blood glucose levels and hemoglobin A1c
equal to or greater than 8% or hospitalization
for diabetic ketoacidosis. |
| |
D. |
Pancreas
retransplantation after one failed primary pancreas
transplant may be considered medically
necessary. |
| III. |
Pancreas
transplantation that does not meet the above criteria
is considered not medically necessary. |
POLICY GUIDELINES
Multiple Transplants
Although there are no standard guidelines regarding
multiple pancreas transplants, the following information
may aid in case review:
- If there is early graft loss resulting from technical
factors (e.g., venous thrombosis), a retransplant
may generally be performed without substantial additional
risk.
- Long-term graft losses may result from chronic
rejection, which is associated with increased risk
of infection following long-term immunosuppression,
and sensitization, which increases the difficulty
of finding a negative cross-match. Some transplant
centers may wait to allow reconstitution of the immune
system before initiating retransplant with an augmented
immunosuppression protocol.
SCIENTIFIC BACKGROUND
This policy is based in part on a 1998 BlueCross BlueShield
Association Technology Evaluation Center (TEC) Assessment
[3], which focused on the pancreas graft survival and
health outcomes associated with both pancreas transplant
alone and pancreas after kidney transplant. Much of
the published literature consists of case series reported
by single centers and registry data. The extant randomized
controlled trials (RCTs) compare immunosuppression
regimens and surgical techniques and therefore do not
address the comparison of pancreas transplantation
to insulin therapy, or simultaneous pancreas/kidney
(SPK) transplant to insulin therapy and hemodialysis.
A 2001 TEC Assessment [4] focused on the issue of pancreas
retransplant. The assessments and subsequent evidence
offer the following observations and conclusions:
Pancreas After Kidney Transplant [3]
Based on pancreas transplant registry data published
at the time of the TEC Assessment, at nearly 3 years,
64% of PAK transplant recipients have a functioning pancreas
compared to 0% of patients receiving a kidney transplant
alone and 77% of SPK transplant patients. PAK transplantation
allows the uremic patient the benefits of a living-related
kidney graft, if available, and the benefits of a subsequent
pancreas transplant that is likely to result in improved
quality of life compared to a kidney transplant alone.
Uremic patients for whom a cadaveric kidney graft is
available but a pancreas graft is not simultaneously
available benefit similarly from a later pancreas transplant.
Changes to the pancreas and kidney allocation system
in 2010 may positively affect the availability of both
organs for SPK transplant and therefore reduce the
need for PAK transplant considerations in diabetic
uremic patients.[5] The inferior graft survival
rate in PAK, however, may be improved with current
immunosuppressive regimens. In 2009, Fridell and colleagues
reported a retrospective review (n=203) of a single
center’s
experience with PAK and SPK since 2003, when current
induction/tacrolimus immunosuppressive strategies became
standard.[6] Of the cases studied, 61 (30%) were PAK
and 142 (70%) were SPK. One-year patient survival rates
were 98% and 95% (PAK and SPK, respectively; p=0.44).
Pancreas graft survival rates at 1 year were observed
to be 95% and 90%, respectively (p=0.28). The authors
conclude that in the modern immunosuppressive era,
PAK should be considered as an acceptable alternative
to SPK in candidates with an available living kidney
donor.
Data that suggest that SPK transplants have a higher
overall graft survival rate than PAK, including kidney
graft survival, have led to the question of whether kidney
transplant alone (KTA) is superior to PAK. In 2009, Kleinclauss
and colleagues retrospectively examined data from diabetic
kidney transplant recipients (n=307) from a single center
and compared renal graft survival rates in those who
subsequently received a pancreatic transplant to those
who did not.[7] The comparative group was analyzed separately
depending on whether they were medically eligible (KTA-E)
for pancreas transplant, but chose not to proceed for
financial or personal reasons, or were ineligible (KTA-I)
for medical reasons. The KTA-I (n=57) group differed
significantly at baseline from both the PAK group (n=175)
and the KTA-E group (n=75) with respect to age, type
of diabetes and dialysis experience; kidney graft survival
rates were lower than either of the other groups, with
1-, 5-, and 10-year rates of 75%, 54%, and 22%, respectively
(p<0.0001). The PAK and KTA-E groups were similar
in age, race, type of diabetes, and dialysis experience.
The authors compared 1-, 5-, and 10-year kidney graft
survival rates in PAK patients with those in the KTA-E
group: 98%, 82%, and 67% versus 100%, 84%, and 62%, respectively,
and concluded that the subsequent transplant of a pancreas
after a living donor kidney transplant does not adversely
affect patient or kidney graft survival rates.
Pancreas Transplant Alone [3]
PTA graft survival has improved in recent years; registry
data available at the time of the TEC Assessment suggest
that 60% of grafts are functioning at 2 years, with
potential insulin independence. In carefully selected
IDDM patients with severely disabling and potentially
life-threatening complications due to hypoglycemia
unawareness and labile diabetes that persists despite
optimal medical management, the benefits of PTA were
judged to outweigh the risk of performing pancreas
transplantation with subsequent immunosuppression.
The majority of patients undergoing PTA are those with
either hypoglycemic unawareness or labile diabetes.
However, other exceptional circumstances may exist
where non-uremic IDDM patients have significant morbidity
risks due to secondary complications of diabetes (e.g.,
peripheral neuropathy) that exceed those of the transplant
surgery and subsequent chronic immunosuppression. Because
there is virtually no published evidence regarding
outcomes of medical management in this very small group
of exceptional diabetic patients, it is not possible
to generalize about which circumstances represent appropriate
indications for pancreas transplantation alone. Case-by-case
consideration of each patient's clinical situation
may be the best option for determining the balance
of risks and benefits.
Noting that nephrotoxic immunosuppression may exacerbate
diabetic renal injury after PTA, Scalea et al reported
a single institutional review of 123 patients who received
131 PTA for development of renal failure. Mean
graft survival was 3.3 years (range, 0–11.3),
and 21 patients were lost to follow-up. Mean estimated
glomerular filtration rate (eGFR) was 88.9 pre-transplantation
versus 55.6 post-transplantation, with mean follow-up
of 3.7 years. All but 16 patients had a decrease in
eGFR, and mean decrement was 32.1 mg/min/1.73. Thirteen
developed end-stage renal disease, which required kidney
transplantation at a mean of 4.4 years. The authors
suggested that patients should be made aware of the
risk and only the most appropriate patients offered
PTA. Future updates of this policy will continue to
follow this clinical topic.
The Pancreas Allotransplantation for Diabetic Nephropathy
and Mild Chronic Renal Failure Stage (PANCREAS) Study
(NCT01067950) is currently recruiting participants
at Nantes University in France. The stated objective
of the study is to assess the superiority of isolated
pancreas transplant to intensive insulin therapy in
type 1 diabetes patients with overt proteinuric nephropathy
and mildly reduced renal function. This is to be an
open-label, randomized trial. The primary combined
endpoint is to be patient mortality and renal function
impairment at 5 years. Secondary endpoints measuring
safety and extrarenal diabetic complications are planned.
If completed, this would represent the first RCT comparing
pancreas transplant to insulin therapy.
Pancreas Retransplantation [4]
For all three types of pancreas transplant (PTA, SPK,
PAK), the survival of a second pancreas transplant
was lower than for the primary transplant of the same
type. However, patients receiving second pancreas transplants
have a good chance of remaining insulin-independent
for three years or more.
There are inadequate data to permit scientific conclusions
regarding the health outcomes associated with a third
or subsequent pancreas transplant.
HIV+ Transplant Recipients
This subgroup of recipients has long been controversial
due to the long-term prognosis for HIV positivity and
the impact of immunosuppression on HIV disease. Although
HIV+ transplant recipients may be a research interest
of some transplant centers, the minimal data regarding
long-term outcome in these patients consist primarily
of case reports and abstract presentations of liver
and kidney recipients. Nevertheless, some transplant
surgeons argue that HIV positivity is no longer an
absolute contraindication to transplant due to the
advent of highly active antiretroviral therapy (HAART),
which has markedly changed the natural history of the
disease. Furthermore, UNOS states that “A potential
candidate for organ transplantation whose test for
HIV is positive should not be excluded from candidacy
for organ transplantation unless there is documented
contraindication to transplantation based on local
policy.”[8] In 2009, the Clinical Practice Committee
of the American Society of Transplantation and the
American Society of Transplant Surgeons proposed that
the presence of AIDS could be considered a contraindication
to kidney transplant unless the following criteria
were present.[9] These criteria may be extrapolated
to other organs:
| • |
CD4 count >200 cells/mm-3
for >6 months
|
| • |
HIV-1 RNA (i.e., viral load) undetectable > 3
months
|
| • |
On stable anti-retroviral therapy >3
months
|
| • |
No other complications from AIDS
(e.g., opportunistic infection, including aspergillus,
tuberculosis, coccidioses mycosis, resistant fungal
infections, Kaposi’s sarcoma, or other neoplasm)
|
| • |
Meeting all other criteria for transplantation
|
In 2006, the British HIV Association and the British
Transplantation Society Standards Committee published
guidelines for kidney transplantation in patients with
HIV disease.[10] As described above, these criteria
may be extrapolated to other organs. The guidelines,
which are similar to those cited above [11], recommend
that any patient with end-stage organ disease with
a life expectancy of at least 5 years is considered
appropriate for transplantation under the following
conditions:
- CD4.200 cells/micro liter for at least 6 months
- Undetectable HIV viremia (<50 HIV-1 RNA copies/mL)
for at least 6 months
- Demonstrable adherence and a stable HAART regimen
for at least 6 months
- Absence of AIDS-defining illness following successful
immune reconstitution after HAART.
The document lists general and disease-specific exclusion
criteria and immunosuppressant protocols. These recommendations
are based on level III evidence (observational studies
and case reports).
. A variety of studies examined various immunosuppressive
regimens [12-16]; however, there were no studies that
examined pancreas retransplant after two failed prior
transplants.
A retrospective analysis of all deceased donor pancreas
transplants performed in the U.S. between 1988 and
1999 revealed that since the mid-1990’s allograft
half-lives ranged from eight to nine years for PTA
transplants to nearly 13 years for SPK transplants.[17] The data indicates that insulin-independence with functioning
grafts can been achieved for longer than 20 years.
REFERENCES
- Hirshberg, B. The cardinal features of recurrent
autoimmunity in simultaneous pancreas-kidney transplant
recipients. Curr Diab Rep. 2010 Oct;10(5):321-2. PMID:
20640940
- Organ Procurement and Transplantation Network (OPTN).
Annual Reports. [cited 01/2011]; Available from: http://optn.transplant.hrsa.gov/latestData/rptData.asp
- TEC Assessment 1998. "Pancreas Transplantation." BlueCross
BlueShield Association Technology Evaluation Center,
Vol. 13, Tab 7.
- TEC Assessment 2001. "Pancreas Retransplantation." BlueCross
BlueShield Association Technology Evaluation Center,
Vol. 16, Tab 23.
- Organ Procurement and Transplantation Network (OPTN).
Policies and Bylaws2. [cited 01/2011]; Available
from: http://optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_7.pdf
- Fridell,
JA, Mangus, RS, Hollinger, EF, et al. The case
for pancreas after kidney transplantation. Clin
Transplant. 2009 Aug-Sep;23(4):447-53. PMID:
19453642
- Kleinclauss,
F, Fauda, M, Sutherland, DE, et al. Pancreas after
living donor kidney transplants in diabetic patients:
impact on long-term kidney graft function. Clin
Transplant. 2009 Aug-Sep;23(4):437-46. PMID:
19496790
- UNOS/OPTN
bylaw: Identification of transmissible diseases
in organ recipients. [cited 08/19/2011];
Available from: http://optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_16.pdf
- Blumberg,
EA, Stock, P. Solid organ transplantation in the
HIV-infected patient. Am J Transplant.
2009 Dec;9 Suppl 4:S131-5. PMID: 20070672
- Bhagani,
S, Sweny, P, Brook, G. Guidelines for kidney transplantation
in patients with HIV disease. HIV Med.
2006 Apr;7(3):133-9. PMID: 16494626
- Steinman,
TI, Becker, BN, Frost, AE, et al. Guidelines for
the referral and management of patients eligible
for solid organ transplantation. Transplantation.
2001 May 15;71(9):1189-204. PMID: 11397947
- Kaufman,
DB, Iii, GW, Bruce, DS, et al. Prospective, randomized,
multi-center trial of antibody induction therapy
in simultaneous pancreas-kidney transplantation. Am
J Transplant. 2003 Jul;3(7):855-64. PMID:
12814477
- Knight,
RJ, Kerman, RH, Zela, S, et al. Thymoglobulin,
sirolimus, and reduced-dose cyclosporine provides
excellent rejection prophylaxis for pancreas transplantation. Transplantation.
2003 Apr 27;75(8):1301-6. PMID: 12717220
- Stratta,
RJ, Alloway, RR, Lo, A, Hodge, E. Two-dose daclizumab
regimen in simultaneous kidney-pancreas transplant
recipients: primary endpoint analysis of a multicenter,
randomized study. Transplantation. 2003
Apr 27;75(8):1260-6. PMID: 12717213
- Reddy,
KS, Stablein, D, Taranto, S, et al. Long-term survival
following simultaneous kidney-pancreas transplantation
versus kidney transplantation alone in patients
with type 1 diabetes mellitus and renal failure. Am
J Kidney Dis. 2003 Feb;41(2):464-70. PMID:
12552511
- Rogers,
J, Ashcraft, EE, Emovon, OE, et al. Long-term outcome
of sirolimus rescue in kidney-pancreas transplantation. Transplantation.
2004 Aug 27;78(4):619-22. PMID: 15446324
- Sutherland,
DE, Gruessner, AC. Long-term results after pancreas
transplantation. Transplant Proc. 2007
Sep;39(7):2323-5. PMID: 17889177
- BlueCross
BlueShield Association Medical Policy Reference
Manual "Allogeneic Pancreas Transplant." Policy
No. 7.03.02
CROSS REFERENCES
Islet
Cell Transplantation, Regence Medical Policy
Manual, Transplant, Policy No. 13
| Codes |
Number |
Description |
| CPT |
48550 |
Donor pancreatectomy
(including cold preservation), with or without duodenal
segment for transplantation |
| |
48551 |
Backbench standard preparation
of cadaver donor pancreas allograft prior to transplantation,
including dissection of allograft from surrounding
soft tissues, splenectomy, duodenotomy, ligation
of bile duct, ligation of mesenteric vessels, and
Y-graft arterial anastomosis from the iliac artery
to superior mesenteric artery and to splenic artery |
| |
48552 |
Backbench reconstruction
of cadaver donor pancreas allograft prior to transplantation,
venous anastomosis, each |
| |
48554 |
Transplantation of pancreatic
allograft |
| HCPCS |
S2065 |
Simultaneous pancreas
kidney transplantation |
| |
S2152 |
Solid organs(s), complete
or segmental, single organ or combination of organs;
deceased or living donor(s), procurement, transplantation,
and related complications; including: drugs; supplies;
hospitalization with outpatient follow-up; medical/surgical,
diagnostic, emergency, and rehabilitative services;
and the number of days of pre- and post-transplant
care in the global definition |
Transplant Section Table of Contents 
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