The impact and importance of achieving a complete haematological response prior to renal transplantation in AL amyloidosis.
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ABSTRACT:
SUBMITTER: Cohen OC
PROVIDER: S-EPMC7244514 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
The impact and importance of achieving a complete haematological response prior to renal transplantation in AL amyloidosis.
Cohen Oliver C OC Law Steven S Lachmann Helen J HJ Sharpley Faye F Ravichandran Sriram S Mahmood Shameem S Sachchithanantham Sajitha S Whelan Carol J CJ De Azcona Naharro Ana Martinez AM Fontana Marianna M Hawkins Philip N PN Gillmore Julian D JD Wechalekar Ashutosh D AD
Blood cancer journal 20200522 5
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Project description:Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p = .003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p = .001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p = .02) and higher frequency of renal response (100% vs. 68%; p = .005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.
| S-EPMC7372715 | biostudies-literature
Project description:IntroductionThe new kidney allocation system (KAS) prioritizes patients based on date of dialysis initiation or waitlisting, whichever is earlier. We hypothesized that this change would increase transplant rates for patients with prolonged pretransplant dialysis times (DT) and aimed to assess the impact of prolonged DT on post-transplant outcomes.MethodsWe used United Network for Organ Sharing registry data to assess outcomes for patients added to the renal transplant waitlist from January 1, 1998 to December 31, 2010 and patients transplanted from January 1, 1998 to December 3, 2012.ResultsCompared with patients transplanted pre-emptively, patients with <5 years, 5-9 years, and ≥10 years DT had progressively decreased graft and patient survival (P < .001). The rates of short-term complications including delayed graft function, graft loss within 30 days, and patient death within 30 days were significantly higher in cohorts with ≥10 years DT than in cohorts with less DT (P < .001).ConclusionsPatients with pretransplant DT of ≥10 years had worse outcomes than patients pre-emptively transplanted or transplanted with shorter DT. Durations of dialysis dependence beyond 10 years were associated with further deterioration in short-term but not long-term post-transplant outcomes.
| S-EPMC6023748 | biostudies-literature
Project description:AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible-for the first time-to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.
| S-EPMC10971215 | biostudies-literature
Project description:BackgroundHistorically, kidney transplantation has been considered inappropriate for most patients with AL amyloidosis-associated kidney failure because of concerns about recurrent disease in the allograft and poor long-term survival. With improvements in rates and durability of hematologic responses and survival that have accompanied treatment advances, a greater proportion of patients with AL amyloidosis may be suitable for kidney transplantation. However, there are no widely accepted criteria for kidney transplant eligibility for this patient population.MethodsWe administered surveys electronically to transplant nephrologists and amyloidosis experts at a geographically diverse set of academic medical centers in the United States. Questions were designed to elucidate views about suitability and timing of kidney transplantation for patients with AL amyloidosis-associated kidney failure.ResultsThe survey was completed by 20 (65%) of invited amyloidosis experts and 20 (29%) of invited transplant physicians. Respondents indicated that, for patients with AL amyloidosis, most transplant nephrologists have limited experience with both determining eligibility for and providing care after kidney transplantation. Most transplant nephrologists and amyloidosis experts viewed anticipated patient survival as the most important determinant of suitability for kidney transplantation. Compared with transplant program respondents, amyloidosis program respondents reported a higher degree of confidence in determining suitability for kidney transplantation, were comfortable proceeding with kidney transplantation earlier after patients attained a hematologic response, and were less concerned about extrarenal amyloid involvement as a barrier to kidney transplantation. In both groups, most respondents indicated that there is a lack of consensus between amyloidosis and kidney transplant physicians about criteria for determining suitability for kidney transplantation.ConclusionViews about criteria for kidney transplantation for patients with AL amyloidosis-associated kidney failure differed between amyloidosis and transplant nephrology program respondents, with amyloidosis specialists generally favoring a less-restrictive approach to transplant eligibility. The findings suggest a need for consensus building across specialties.
| S-EPMC8986034 | biostudies-literature
Project description:De novo sequencing of amyloid fibrils from renal AL amyloidosis based on LC-MS/MS
2025-07-25 | PXD066587 |
Project description: Not available
| S-EPMC5893431 | biostudies-literature
Project description: Not available
| S-EPMC7210159 | biostudies-literature
Project description:Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly longer in patients with complete and very good partial hematologic responses (CR + VGPR) compared to less than VGPR (9 versus 6.8 years; HR: 1.5, P = 0.04 [95% CI: 1-2.1]) at renal transplantation. Median graft survival was 7.8 years and was better in the CR + VGPR group (8.3 vs 5.7 years, HR: 1.4, P = 0.05 [95% CI: 1-2]). The frequency and time to amyloid recurrence in the graft was also lower (16% vs 37%, p = 0.01) and longer (median time not achieved vs 10 years, p = 0.001) in the CR + VGPR group. Comparing CR vs. VGPR there was no difference in overall or graft survival. Although 69 patients (29%) experienced hematologic relapse, treatment effectively prevented graft loss in the majority (87%). Renal transplantation in selected AL amyloidosis patients is associated with extended overall and renal graft survival. Patients with hematologic CR or VGPR have the most favorable outcomes, and these patients should be considered for renal transplantation.
| S-EPMC9388492 | biostudies-literature
Project description:Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient's state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.
| S-EPMC5529729 | biostudies-other
Project description:BackgroundsPublished literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial.Case presentationHere we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis. The patient received a total of six courses of CyBorD chemotherapy. She had achieved complete hematologic remission after two courses of chemotherapy but consistently had large amount of proteinuria over 10 g/day during follow up. A repeat renal biopsy was performed nine months after the first one and indicated mild to moderate increase of amyloid deposits as well as significant glomerulosclerosis and interstitial lesions, suggesting a lack of histological renal improvement despite her satisfactory hematologic response.ConclusionsThis case indicated renal involvement in AL amyloidosis could progress after successful hematologic treatment, and supported the value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission.
| S-EPMC8974030 | biostudies-literature