Alterations of the Female Reproductive System in Recipients of Islet Grafts

Cure, Pablo; Pileggi, Antonello; Froud, Tatiana; Norris, Paul; Baidal, David; Cornejo, Agustin; Hafiz, Muhammad M.; Ponte, Gaston; Poggioli, Raffaella; Yu, Jeannie; Saab, Amanda; Selvaggi, Gennaro; Ricordi, Camillo; Alejandro, Rodolfo

doi:10.1097/01.tp.0000147301.41864.c0

Cited by 48 publications

(39 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They only became severe if the sirolimus was not reduced quickly enough. Acne was surprisingly common, as were ovarian cysts in premenopausal women, with the latter recently reported by the Miami group (42). Edema was resistant to all standard measures in 12% and was severe enough to warrant changes in immunosuppressive therapy, as has been reported (43).…”

Section: Discussionmentioning

confidence: 61%

Five-Year Follow-Up After Clinical Islet Transplantation

Ryan

Paty²,

Senior³

et al. 2005

Diabetes

1,513

1,243

View full text Add to dashboard Cite

Islet transplantation can restore endogenous ␤-cell function to subjects with type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as of 1 November 2004. Their mean age was 42.9 ؎ 1.2 years, their mean duration of diabetes was 27.1 ؎ 1.3 years, and 57% were women. The main indication was problematic hypoglycemia. Forty-four patients completed the islet transplant as defined by insulin independence, and three further patients received >16,000 islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those who became insulin independent received a total of 799,912 ؎ 30,220 IE (11,910 ؎ 469 IE/kg). Five subjects became insulin independent after one transplant. Fifty-two patients had two transplants, and 11 subjects had three transplants. In the completed patients, 5-year follow-up reveals that the majority S ustained C-peptide production and successful insulin independence after pancreatic islet transplantation in type 1 diabetic patients was reported over 4 years ago by the Edmonton group (1). This reality became possible with the use of newer, more potent immunosuppressive agents, the avoidance of corticosteroids, and high-quality islet preparations, although typically two islet infusions were necessary to attain insulin independence. Over this period, other centers have been able to replicate the initial success of the Edmonton Protocol with further refinements in technique (2-5), and islet transplantation is increasingly being used (6 -8).However, the need for ongoing immunosuppressive therapy and the scarcity of donor islets have precluded the widespread adoption of islet transplantation. The main indications for solitary islet transplantation have been frequent recurrent hypoglycemia or labile glucose values that have defied optimization of medical therapy. An additional hoped for, but unproven, benefit has been stabilization or improvement of diabetes complications with the achievement of stable good glycemic control. Now, 5 years after the first islet transplant was performed with the Edmonton Protocol, we have had the opportunity to review the outcomes in terms of C-peptide secretion, insulin independence, correction of hypoglycemia and lability, acute complications encountered, chronic problems related to immunsuppressive therapy, and some assessment of the effect on diabetes complications. RESEARCH DESIGN AND METHODSAs of 1 November 2004, 65 patients have received islet transplants at the University of Alberta. Four other subjects were transplanted as part of the Immune Tolerance Network trial of islet transplantation and will be reported independently. One further subject was transplanted with a preparation from a pediatric donor that had many trapped islets. This subject had primary nonfunction of the graft, and the data from this patient are not included in this report. At the time of the transplant, the mean age of the 65 patients was 42.9 Ϯ 1.2 years, their duration of diabetes was 27.1 Ϯ 1.3 years, and 57% were women. Their median weight was 68.5 kg (interq...

show abstract

Section: Discussionmentioning

confidence: 61%

Five-Year Follow-Up After Clinical Islet Transplantation

Ryan

Paty²,

Senior³

et al. 2005

Diabetes

1,513

1,243

View full text Add to dashboard Cite

show abstract

“…Observational data suggest a potential for ovarian toxicity, but this issue has not been evaluated in randomized, controlled trials. 2 In the Suisse ADPKD study (ClinicalTrials.gov number, NCT00346918), a randomized, controlled trial conducted at the University Hospital Zurich from March 2006 through March 2010, we reviewed the occurrence of menstrual-cycle disturbances and the appearance of ovarian cysts 3 in 39 women with ADPKD, an inherited kidney disease that is not known to affect ovarian morphology and function. 4,5 The trial was conducted in accordance with the principles of the Declaration of Helsinki, the Good Clinical Practice guidelines of the International Conference on Harmonization, and local regulatory requirements.…”

Section: Ovarian Toxicity From Sirolimusmentioning

confidence: 99%

Ovarian Toxicity from Sirolimus

Braun¹,

Young²,

Reiner³

et al. 2012

N Engl J Med

View full text Add to dashboard Cite

“…During follow-up, all recipients had multiple immunosuppression-related side-effects, with similar frequency and severity previously reported using 'Edmontonlike' protocols (5,42,43). The most important were: mucocutaneous (oral ulcers, n = 4 recipients), hematological (leucopenia, n = 5; anemia, n = 3), infective (respiratory tract infections, n = 5), metabolic (hyperlipidemia, n = 3) gynecological (dysfunctional menstrual bleeding, requiring endometrial ablation, n = 1), and neuropsychiatric (depression and anxiety, requiring reduction of immunosuppression, n = 1).…”

Section: Islet Transplant Tolerance By Hematopoietic Stem Cellsmentioning

confidence: 70%

Combined Islet and Hematopoietic Stem Cell Allotransplantation: A Clinical Pilot Trial to Induce Chimerism and Graft Tolerance

Mineo

Ricordi

et al. 2008

American Journal of Transplantation

View full text Add to dashboard Cite

To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 ± 2113 IEQ/kg) followed by high doses of donor HSC (4.3 ± 1.9 × 10 6 HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFa antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 ± 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 ± 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 ± 0.48%), highly reduced at 1-year (0.20 ± 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.

show abstract

Alterations of the Female Reproductive System in Recipients of Islet Grafts

Abstract: Our findings suggest that pre- and posttransplant evaluation of female patients should include menstrual history, baseline pelvic ultrasound, and hormonal levels to assess the presence and monitor the progression of such alterations.

Cited by 48 publications

References 13 publications

Five-Year Follow-Up After Clinical Islet Transplantation

Five-Year Follow-Up After Clinical Islet Transplantation

Ovarian Toxicity from Sirolimus

Combined Islet and Hematopoietic Stem Cell Allotransplantation: A Clinical Pilot Trial to Induce Chimerism and Graft Tolerance

Contact Info

Product

Resources

About