CSII therapy achieves and maintains its efficacy mainly in terms of reducing severe hypoglycaemia. In the whole group of patients, the reduction in HbA1c is transient and disappears after 5 years.
Although a transient phenomenon, PCGM can be useful in the short term in improving metabolic and clinical profile of suboptimally controlled T1DM subjects, including those with repeated hypoglycemia.
Background. Allosensitization has been reported after discontinuation of immunosuppression following graft failure in islet transplantation (ITx) recipients, though duration of its persistence is unknown. Methods. We evaluated 35 patients with type 1 diabetes who received ITx, including 17 who developed graft failure (ITx alone, n = 13; ITx plus bone marrow-derived hematopoietic stem cells, n = 4) and 18 with persistent graft function. Panel-reactive antibody (PRA) was measured yearly for the duration of graft function within 1 y after graft failure at enrollment and yearly thereafter. Results. In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 y postgraft failure, and 46% (6/13) developed donor-specific anti-HLA antibodies (DSA to 2 ± 1 donors) during follow-up. The degree of sensitization was variable (cPRA ranging between 22% and 100% after graft failure). Allosensitization persisted for 7–15 y. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88%–98%) and DSA positivity persisted for 15 y in 75% (3/4) of subjects. Conclusions. Allosensitization was minimal while subjects remained on immunosuppression, but after discontinuation of immunosuppressive therapy, the majority of subjects (77%) became allosensitized with persistence of PRA positivity for up to 15 y. Persistence of allosensitization in this patient population is of clinical importance as it may result in longer transplant waiting list times for identification of a suitable donor in the case of requiring a subsequent transplant.
Allosensitization (PRA+) has been reported after discontinuation of immunosuppression (IS) following graft failure (GF) in islet transplant (ITx) recipients. Persistence of PRA+ after GF is unknown. Thirteen ITx alone (IA) and 5 ITx subjects who also received donor CD34+ hematopoietic stem cells (IBM) and developed GF enrolled in the study “Allosensitization After Islet Transplantation.” Panel reactive antibodies (PRA) were measured yearly while having graft function, within 1 year post-GF and yearly after study enrollment. Two subjects who developed GF but remained on mycophenolate mofetil (MMF) for 2 years and 18 subjects with persistent graft function (15 IA and 3 islet after kidney [IAK]) were also evaluated. 80% IBM subjects developed high PRA+ (>89%) (Figure 1a) while 70% IA subjects were PRA+ at enrollment (0.8-6 years post-GF) and 42%-55% were PRA+ throughout follow-up. PRA results were variable (Figure 1b). The 2 subjects taking MMF post-GF and 1 subject who required IVIG pre-GF (for parvovirus infection) were not PRA+. Four subjects with persistent graft function by 10 years became PRA+ (2 IA and 2 IAK; Figure 1c). After stopping IS, 70% IA subjects became PRA+ with persistence of PRA (although variable) for at least 10 years post-GF. PRA+ was higher in IBM compared to IA subjects. While receiving IS, PRA+ was minimal. Persistence of PRA+ remains a concern due to potentially prolonged wait list time for subsequent organ transplantation if needed. Disclosure P. Rios: None. D. Baidal: None. N. Padilla: None. A.M. Alvarez Gil: None. S. Madiraju: None. J. Ambut: None. A.M. Mantero: None. S. Messinger Cayetano: None. C. Ricordi: None. R. Alejandro: None.
Aim: To evaluate the efficacy of Lenalidomide (Len) as compassionate use in relapsed or progressive Multiple Myeloma (MM) up to its approval in Spain. Patients and Methods: GEM-PETHEMA designed a transverse and retrospective, multicenter analysis of MM cases which Len compassionate use was requested until December, 2007. The decision to treat these patients was previous and independent from the decision to conduct the present analysis and depended only on the clinical criteria of the responsible doctors. At least, one response assessment was a must for efficacy analysis. Results: 111 MM patients have been included. Eligible patients for efficacy were 103. Mean age was 65.7 (38–85); 53 m, 50 f. Previous median lines of therapy were 3 (1–8): 92 (89.3%) have received bortezomib; 37 (35.9%) autologous PBSCT and 26 (25.2%) thalidomide. Extramedullary plasmocitomas were present in 25 (24.3%). Mean Len dose was 22.8 mg (± 4.9): 82 (79.6%) received the standard dose and schedule (25 mg d for 3 w every 4 w) and 21 (20.4%) received less dose and/or different schedule. 92 (89.3%) received Dexametasone (mean dose 58.33 mg/w) [± 35.8]). Response: 4 (3.9%) sCR, 11 CR (10.7%), 12 VGPR (11.7%), 41 PR (39.8%), 20 SD (19.4%), 13 PD (12.6%), 2 NE (1.9). Among groups, response equal or superior to PR was observed in all settings: 64.1% in prior exposed to bortezomib, 46.1% in prior exposed to thalidomide and 40.0% in patients with extramedullary plasmocitomas. Previous transplant, the number of previous lines received, renal failure, age, or cytogenetic did not affect significantly the overall response rate. Median duration of treatment was 7.7 m (1–21); median TTP was 8.3 m and median global survival since starting Len therapy was 11 m (6–22). Median survival since diagnostic was 49 m (40–60). At the time of analysis, 46 (45.5%) patients were still on Len therapy, and 72 (79.6%) were alive. Toxicity: ≥ grade II: neutropenia, 51 (46.4%); thrombocytopenia, 39 (35.5%); DVT, 5 (4.5%); rash, 3 (2.7%); neutropenic fever, 8 (7.3%); others, 13 (11.8%). DVT/PE prophylaxis was used in 89 (86.4%) patients: LWMH in 43.8 % and low dose aspirin in 48.3 %. No PE was reported. Conclusions: Lenalidomide is effective in this heavily pre-treated MM population-progressive or refractory to standard therapy-even in different clinical settings. The most frequent association to Len was intermediate dose of Dex. Although response rate was superior in patients exposed previously to bortezomib, no differences on duration and survival were observed. Patients with extramedullary plasmocitomas showed also response. Toxicity, mainly myelosupression was predictable and manageable with dose adjustments and cytokine support.
Background: Polycystic ovarian syndrome (PCOS) mimics non-classic congenital hyperplasia (NCCAH), presenting with hyperandrogenic symptoms. NCCAH is usually diagnosed later in life, where 21-hydroxylase (21OHD) is the most common deficiency. There are more than 300 mutations in 21OHD, being V281L one of the described mutations. Clinical Case: 23 y/o female patient G0P0 comes to the office complaining of irregular periods, frontal hair loss, weight gain, acne and hirsutism. She has had noticed these changes since menarche; however, her acne was getting worse. Was seen 2 months prior to presentation by her gynecologist who order a free Testosterone that was elevated (6.4 pg/mL, n<4.2 pg/mL), with normal TSH (1.1 uIU/mL, n,0.45-4.5). She was not taking any medication. Her mother has history of 2 spontaneous abortions and her sister has acne and hirsutism as well. On physical exam BMI was 26, it was noticed comedones and papules on her face, back and shoulders. Ferriman-Gallwey scale was >8. At the initial visit due to the clinical scenario, it was thought that she had hyperandrogenic syndrome, probably secondary to PCOS. Serum blood test were ordered and showed an elevated total testosterone (71 ng/dL, n,8-48ng/dL), free testosterone (8.4 pg/mL, n<4.2 pg/mL), 17- OH pregnenolone performed by liquid chromatography-tendem mass spectrometry (LC-MS/MS) was (429 ng/dL, n, 35-290 ng/dL luteal phase) and androstenedione LC-MS/MS (1941 ng/dL, n, 41-262 ng/dL) which confirmed NCCAH diagnosis due to 21OHD. She had no desire to become pregnant at the time of evaluation; however, was concern about fertility and genetics. Was started on OCPs and genetic testing was positive for V281L mutation in the CYP21A2 gene, being homozygous for this mutation. Three months after, her acne and frontal hair loss were better, and a trial of spironolactone 50 mg daily, was prescribed. For her sister and mother was suggested to consult endocrinology, due to possible same disease. Conclusion: this case highlights the importance of recognizing NCCAH as a cause of hyperandrogenism. Molecular genetic analysis should be offered with genetic counseling to patients, since they can carry a severe allele which can affect their progeny. Clinicians should be aware of the importance of family history when diagnosing NCCAH on their patients; for detection, treatment and genetic counseling of NCCAH on family members as well, as found in this case.
Background: Novel immune checkpoint proteins inhibitors, such cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) like ipilimumab could produce hypophysitis as a side effect with a prevalence between 0 to 10%. There are no guidelines in how to monitor patients receiving similar agents. We present a case that was follow up hormonally and developed hypophysitis. Clinical Case: A 63-year-old male presented in 2015 with severe frontal headache that lasted 4 days with no improvement with Ibuprofen and fatigue 5 days after receiving third dose of ipilimumab for metastatic malignant melanoma. He denied nausea, vomiting, visual symptoms. Magnetic resonance (MRI) demonstrated a diffuse pituitary enlargement. Laboratory results showed decreased hormones like: cortisol (0.5mcg/dl, n:4-22mcg/dl), freeT4 (0.36 ng/dl, n:0.8-1.8ng/dl), TSH (0.36 mIU/L, n:0.40-4.5mIU/L) prolactin (<1ng/ml, n 2-18 ng/ml), free testosterone (33.6 pg/ml, n:35-155pg/ml) and normal IGF-1 (62 ng/ml, n:41-279) consistent with panhypopituitarism in the setting of hypophysitis secondary to ipilimumab. Cortisol and thyroid hormones levels where checked before beginning ipilimumab and after receiving first dose and were within normal limits. After patient received the second dose, patient had an episode of colitis which lasted 10 days, which required prednisone 40 mg for 1 week and then it was tapered for another 2 weeks. At that point cortisol was checked which was normal (9.9 mcg/l n:4-22mcg/dl), however patient was on steroids. Patient received third dose of ipilimumab and then he developed severe headache and was diagnosed with hypophysitis. Patient was started on dexamethasone high doses, which was tapper down and switched to hydrocortisone 20 mg am and 10 at pm and was started on levothyroxine 137 mcg daily. Two months after diagnosis an MRI was repeat which did not show any pituitary enlargement, however patient had persistent panhypopituitarism on laboratory results. Four months after diagnosis was started on testosterone replacement therapy. Last visit was in 2018 patient was without fatigue, he is on hydrocortisone 15mg am, 10mg pm, levothyroxine 175 mcg, and testosterone gel every day. His cortisol is decreased (1 mcg/dl , n:4-22mcg/dl), IGF-1 now is low (37 ng/ml n:41-279), prolactin is decrease (1.3 ng/ml, n 2-18 ng/ml), free T4 normal on replacement (1.1 ng/dl, n:0.8-1.8ng/dl), normal free testosterone on replacement (57.6 pg/ml, n:35-155pg/ml). Conclusion: endocrinopathies are seen up to 10% in patients on CTLA-4 , therefore awareness of more serious deficits like hypophysitis should need to be promptly recognized and follow up is recommended, like we are implementing this approach in our institution.
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