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Registry Report

Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2019: Islet Donations, Islet Isolations, and Islet Transplants

Webster, Angela C. PhD1,2; Hedley, James A. MBiostat2; Anderson, Patricia F. MN1; Hawthorne, Wayne J. PhD1,3; Radford, Toni DipN4; Drogemuller, Chris PhD4,5; Rogers, Natasha PhD1,3; Goodman, David PhD6,7; Lee, Melissa H. MBBS7,8; Loudovaris, Thomas PhD9; Kelly, Patrick J. PhD2; on behalf of the Australian Islet-cell Transplant consortium

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doi: 10.1097/TXD.0000000000001014
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OVERVIEW OF ISLET TRANSPLANTATION

Islet transplants are a treatment for patients with type 1 diabetes who have hypoglycemic unawareness and/or severe metabolic instability and are sensitive to insulin, but who have minimal or no kidney impairment. Whole donor pancreas organs are processed aiming to produce a concentrate of islet cells >4000 islet equivalent numbers/kg in a volume of <9 mL. Islet transplant recipients generally require >1 islet transplant to become insulin independent.

Data for islet transplant donors and recipients in Australia are still sparse.1 The islet transplant program started in 2002. There are 2 islet isolation facilities in Australia: St Vincent’s Hospital Melbourne in Victoria, and Westmead hospital in New South Wales. There are 3 active islet transplant centers: the National Pancreas Transplant Unit at Westmead Hospital, St Vincent’s Hospital Melbourne, and the Royal Adelaide Hospital. There is no islet transplant program in New Zealand. This report contains information about allogenic islet transplants (ie, islets from a deceased donor).

In this year’s report, we have added as much data as we have available on the islet program in Australia to date and expanded description to capture the waiting list for islet transplants, donor, and recipient characteristics. We have only reported islet donors and procedures that were intended to be used for an islet transplantation and not islet isolation procedures that were undertaken only for research purposes. Some donor isolations intended for transplantation did not proceed to transplantation, generally because the pancreas processing failed set release criteria, with the major reason being insufficient concentration of islet cells.

ISLET WAITING LIST ACTIVITY

The islet program waiting list is intentionally not long. Table 1 shows the number of patients referred for an islet transplant in 2018 by state of residence and the transplant center they were referred to. Table 2 shows the number of patients accepted onto an islet waiting list during 2018, whereas Table 3 shows the islet waiting list activity over time.

TABLE 1.
TABLE 1.:
Referrals for allogenic islet transplant during 2018 by state of residence and transplant center
TABLE 2.
TABLE 2.:
Patients accepted onto a waiting list for an allogenic islet transplant during 2018 by state of residence and transplant center
TABLE 3.
TABLE 3.:
Islet waiting list status over time: Westmead Hospital (NSW), St Vincent’s Hospital (VIC), and Royal Adelaide Hospital (SA)

ISLET ISOLATIONS

Sometimes when pancreas donations are processed for islet transplantation, the resulting islets do not meet transplant release criteria. The decision to proceed with transplantation is made once release testing is complete and the quality and quantity of islet cells is known. Islet isolation procedures follow good manufacturing procedure guidelines as set out by the Australian Therapeutic Goods Administration. Isolations occur at 1 of 2 dedicated isolation facilities at Westmead (Sydney) and St Vincent’s Institute (Melbourne), both associated with their respective local hospitals Westmead and St Vincent’s Hospital. Occasionally preparations are sent between Melbourne and Sydney; however, Royal Adelaide Hospital has no islet isolation facility and is dependent on islets from either Westmead or St Vincent’s Institute, with the latter being the main provider of islets. A summary of islet cell isolation activity by center and year in presented in Table 4.

TABLE 4.
TABLE 4.:
Summary of allogenic islet cell isolation activity, for all centers in Australia

The donor characteristics of islet cell donor isolations are presented in Table 5. Donor characteristics are influenced in part by the Australian donor pancreas allocation policy that allocates pancreata for both pancreatic islet isolation and for whole pancreas transplantation. This policy is available at https://www.tsanz.com.au/organallocationguidelines/index.asp.

TABLE 5.
TABLE 5.:
Donor characteristics for allogenic islet isolations (all centers)

Donors who provided pancreata that resulted in islet isolations that proceeded to transplantation are summarized in Table 6.

TABLE 6.
TABLE 6.:
Donor characteristics for allogenic islet isolations which resulted in transplantation in 2018

ISLET TRANSPLANT RECIPIENTS

Figure 1 illustrates the number of islet cell transplants in Australia between 2002 and 2018. The transplants were performed in Westmead (68), St Vincent’s (30), and Royal Adelaide (18) Hospitals. In 2018, 5 transplants were performed at Westmead, 7 at St Vincent’s, and 2 at the Royal Adelaide.

FIGURE 1.
FIGURE 1.:
Allogenic islet transplant activity 2002–2018, by transplanting center. NSW, New South Wales; SA, South Australia; VIC, Victoria.

The characteristics of donor and recipient matches according to sex and blood group distributions for all centers are presented in Tables 7 and 8.

TABLE 7.
TABLE 7.:
Cross tabulation of recipient and donor sex, 2002–2018
TABLE 8.
TABLE 8.:
Cross tabulation of recipient and donor blood groups, 2002–2018, for allogenic islet transplants undertaken in Australia

State of residence of recipients receiving an islet transplant in 2018, by the order of their transplant, is presented in Table 9.

TABLE 9.
TABLE 9.:
Allogenic islet transplant recipients by state of residence and number of transplants received (all centers, 2018)

The states of residence of donors and recipients for each transplantation are shown in Table 10, stratified by the transplant center.

TABLE 10.
TABLE 10.:
Cross tabulation of allogenic islet donor and recipient state of residence 2002–2018

Characteristics of islet recipients over time are shown in Table 11.

TABLE 11.
TABLE 11.:
Characteristics of allogenic islet cell transplant recipients in Australia by y of first transplant

The time from activation on the waiting list to first islet transplant for 2002–2018 is presented in Figure 2. Data were available for 101 patients added to the waiting list before December 31, 2018, 58 of whom have received at least 1 transplant during this period. However, the date of waitlisting is known for only 59 patients, 21 of whom received at least 1 transplant as of December 31, 2018. The median time to first transplant has not yet been reached (25th percentile: 0.99 y).

FIGURE 2.
FIGURE 2.:
Time from activation on a waiting list to first allogenic islet transplant.

The time from first to second islet transplant for 2002–2018 is presented in Figure 3. Recipients waited a median of 1.10 y from first transplant to receiving a second transplant (interquartile range: 0.36–13.63 y).

FIGURE 3.
FIGURE 3.:
Time from first to second allogenic islet transplant. This figure includes some patients who do not require a second transplant and hence will never receive one.

The time from second to third islet transplant for 2002–2018 is presented in Figure 4. The median time from second transplant to third transplant has not yet been reached (25th percentile: 0.84 y), likely due to many recipients not requiring a third transplant.

FIGURE 4.
FIGURE 4.:
Time from second to third allogenic islet transplant. This figure includes some patients who do not require a third transplant and hence will never receive one.

The distribution of C-peptide measurements over time after first islet infusion (but before second islet infusion) is presented in Figure 5; the distribution of C-peptide measurements over time after second islet infusion (but before third islet infusion) is presented in Figure 6; and the distribution of C-peptide measurements over time after third islet infusion is presented in Figure 7. The normal range for a person without diabetes is approximately 0.7–3.1 ng/mL.

FIGURE 5.
FIGURE 5.:
Distribution of C-peptide over time since first allogenic islet infusion. IQR, interquartile range.
FIGURE 6.
FIGURE 6.:
Distribution of C-peptide over time since second allogenic islet infusion. IQR, interquartile range.
FIGURE 7.
FIGURE 7.:
Distribution of C-peptide over time since third allogenic islet infusion. IQR, interquartile range.

Occurrence of unpredictable hypoglycemia, particularly if frequent, can impact an individual’s quality of life. Ryan et al.2 proposed a symptom score to measure frequency, severity, and degree of unawareness of hypoglycemia experienced by patients with diabetes. The HYPO score was stratified by the recorded level of glucose and summed points for the type of symptoms experienced, whether the sufferer recognized the impending hypoglycemia, and whether outside help was needed to recognize or treat each episode. A greater number of points were scored when glucagon was administered, or an ambulance called. The higher the HYPO score, the worse the impact of hypoglycemia for an individual. A HYPO score of 0 equates with no interference in regular life by hypoglycemic episodes. The maximum score per hypoglycemic episode was 198. The distribution of HYPO score measurements over time after first islet infusion (but before second islet infusion) is presented in Figure 8, the distribution of HYPO score measurements over time after second islet infusion (but before third islet infusion) is presented in Figure 9, and the distribution of HYPO score measurements over time after third islet infusion is presented in Figure 10.

FIGURE 8.
FIGURE 8.:
Distribution of HYPO score2 over time since first allogenic islet infusion. IQR, interquartile range.
FIGURE 9.
FIGURE 9.:
Distribution of HYPO score over time since second allogenic islet infusion. IQR, interquartile range.
FIGURE 10.
FIGURE 10.:
Distribution of HYPO score over time since third allogenic islet infusion. IQR, interquartile range.

The distribution of glycosylated hemoglobin A1c (HbA1c) measurements over time after first islet infusion (but before second islet infusion) is presented in Figure 11; the distribution of HbA1c measurements over time after second islet infusion (but before third islet infusion) is presented in Figure 12; and the distribution of HbA1c measurements over time after third first islet infusion is presented in Figure 13.

FIGURE 11.
FIGURE 11.:
Distribution of HbA1c (%) over time since first allogenic islet infusion. HbA1c, glycosylated hemoglobin A1c; IQR, interquartile range.
FIGURE 12.
FIGURE 12.:
Distribution of HbA1c (%) over time since second allogenic islet infusion. HbA1c, glycosylated hemoglobin A1c; IQR, interquartile range.
FIGURE 13.
FIGURE 13.:
Distribution of HbA1c (%) over time since third allogenic islet infusion. HbA1c, glycosylated hemoglobin A1c; IQR, interquartile range.

Insulin independence is defined as a person being free from insulin use for at least 14 d. There are 20 patients who have achieved insulin independence; 2 patients after their first transplant, 11 patients after their second transplant, and 7 patients after their third transplant. The duration of insulin independence from the time insulin was first ceased for 2002–2018 is presented in Figure 14.

FIGURE 14.
FIGURE 14.:
Duration of insulin independence from time first ceased.

ACKNOWLEDGMENTS

This paper is presented on behalf of the Australian Islet-cell Transplant consortium, who have all contributed to the manuscript: Professor Philip J. O’Connell, Associate Professor Natasha Rogers, Professor Wayne Hawthorne, Associate Professor D. Jane Holmes-Walker, Ms Patricia Anderson, Ms Lindy Williams, Professor Thomas W. Kay, Professor Richard J. MacIsaac, Associate Professor David Goodman, Associate Professor Glenn M. Ward, Dr Thomas Loudovaris, Ms Kathy Howe, Professor P. Toby Coates, Professor David Torpy, Dr Anthony Roberts, Dr Chris Russell, Dr Santosh Olakkengil, Dr Chris Drogemuller, and Ms Toni Radford.

REFERENCES

1. Webster AC, Hedley JA, Anderson PF, et al. Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2018-islet donations, islet isolations, and islet transplants. Transplant Direct. 2019; 5:e421. doi:10.1097/TXD.0000000000000851
2. Ryan EA, Shandro T, Green K, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes. 2004; 53:955–962. doi:10.2337/diabetes.53.4.955
Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.