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Importance: Kidney light chain (AL) amyloidosis is associated with a risk of progression to kidney replacement therapy (KRT) and death. Several studies have shown that a greater reduction in proteinuria following successful anticlonal therapy is associated with improved outcomes., Objective: To validate graded kidney response criteria and their association with kidney and overall survival (OS)., Design, Setting, and Participants: This retrospective, multicenter cohort was conducted at 10 referral centers for amyloidosis from 2010 to 2015 and included patients with kidney AL amyloidosis that was evaluable for kidney response and who achieved at least hematologic partial response within 12 months of diagnosis. The median follow-up was 69 (54-88) months. Data analysis was conducted in 2023., Exposure: Four kidney response categories based on the reduction in pretreatment 24-hour urine protein (24-hour UP) levels: complete response (kidCR, 24-hour UP ≤200 mg), very good partial response (kidVGPR, >60% reduction in 24-hour UP), partial response (kidPR, 31%-60% reduction), and no response (kidNR, ≤30% reduction). Kidney response was assessed at landmark points (6, 12, and 24 months) and best kidney response., Main Outcomes and Measures: Cumulative incidence of progression to KRT and OS., Results: Seven-hundred and thirty-two patients (335 women [45.8%]) were included, with a median (IQR) age of 63 (55-69) years. The median (IQR) baseline 24-hour proteinuria and estimated glomerular filtration rate was 5.3 (2.8-8.5) g per 24 hours and 72 (48-92) mL/min/1.73m2, respectively. In a competing-risk analysis, the 5-year cumulative incidence rates of progression to KRT decreased with deeper kidney responses as early as 6 months from therapy initiation (11%, 12%, 2.1%, and 0% for kidNR, kidPR, kidVGPR, and kidCR, respectively; P = .002) and were maintained at 12 months and 24 months and best kidney response. Patients able to achieve kidCR/kidVGPR by 24 months and at best response had significantly better OS compared with kidPR/kidNR. Kidney progression, defined as a 25% or greater decrease in estimated glomerular filtration rate, was associated with cumulative incidence of progression to KRT and OS., Conclusions and Relevance: The results of this cohort study suggest that graded kidney response criteria offers clinically and prognostically meaningful information for treating patients with kidney AL amyloidosis. The response criteria potentially inform kidney survival based on the depth of reduction in 24-hour proteinuria levels and demonstrate an OS advantage for those able to achieve kidCR/kidVGPR compared with kidPR/kidNR. Taken together, achievement of at least kidVGPR by 12 months is needed to ultimately improve kidney and patient survival.

In the phase 3 QUAZAR AML-001 trial (NCT01757535) of patients with acute myeloid leukaemia (AML) in remission following intensive chemotherapy (IC) and ineligible for haematopoietic stem cell transplant (HSCT), oral azacitidine (Oral-AZA) maintenance significantly prolonged overall survival (OS) versus placebo. The impact of subsequent treatment following maintenance has not been evaluated. In this post hoc analysis, OS was estimated for patients who received subsequent AML therapy, and by regimen received (IC or lower-intensity therapy). First subsequent therapy (FST) was administered after treatment discontinuation in 134/238 Oral-AZA and 173/234 placebo patients. OS from randomization in patients who received FST after Oral-AZA versus placebo was 17.8 versus 12.9 months (HR: 0.82 [95% CI: 0.64-1.04], median follow-up: 56.7 months); OS from FST was similar between arms. Among patients who received injectable hypomethylating agents as FST, median OS was 8.2 versus 4.9 months in the Oral-AZA versus placebo groups (HR: 0.66 [95% CI: 0.41-1.06]). Forty-eight patients (16/238 Oral-AZA, 32/234 placebo) received HSCT following treatment discontinuation, including six Oral-AZA patients still in first remission; Oral-AZA OS benefit persisted when censoring these patients. Oral-AZA maintenance can prolong AML remission duration without negatively impacting survival outcomes after salvage therapies., (© 2023 Bristol Myers Squibb and The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Binary cardiac response assessment using cardiac biomarkers is prognostic in light chain amyloidosis. Previous studies suggested four-level cardiac responses using N-terminal prohormone of brain natiuretic peptide improves prognostic prediction. This study was designed to validate graded cardiac response criteria using N-terminal prohormone of brain natiuretic peptide/brain natiuretic peptide., Patients and Methods: This retrospective, multicenter study included patients with light chain amyloidosis who achieved at least a hematologic partial response (PR) and were evaluable for cardiac response. Four response criteria were tested on the basis of natriuretic peptide response depth: cardiac complete response (CarCR), cardiac very good partial response (CarVGPR), cardiac PR (CarPR), and cardiac no response (CarNR). Response was classified as best response and at fixed time points (6, 12, and 24 months from therapy initiation). The study primary outcome was overall survival., Results: 651 patients were included. Best CarCR, CarVGPR, CarPR, and CarNR were achieved in 16%, 26.4%, 22.9%, and 34.7% of patients, respectively. Patients in cardiac stage II were more likely to achieve CarCR than patients in cardiac stage IIIA and IIIB (22% v 13.5% v 3.2%; P < .001). A deeper cardiac response was associated with a longer survival (5-year overall survival 93%, 79%, 65%, and 33% for CarCR, CarVGPR, CarPR, and CarNR, respectively; P < .001). Fixed time-point analyses and time-varying covariates Cox regression analysis, to minimize survivorship bias, affirmed the independent survival advantage of deeper cardiac responses. Four-level response performed better than two-level response as early as 12 months from therapy initiation., Conclusion: Graded cardiac response criteria allow better assessment of cardiac improvement compared with the traditional binary response system. The study re-emphasizes the importance of early diagnosis, which increases the likelihood of deep cardiac responses.

High-dose chemotherapy and autologous hematopoietic cell transplantation is an effective consolidation therapy in lymphoma; however, its use in elderly patients has been limited because of concerns for greater toxicity in this group. We investigated the toxicities of carmustine, etoposide, cytarabine, and melphalan (BEAM) and autologous hematopoietic cell transplantation (AHCT) in 346 patients in 2 age groups: 279 patients aged 60 to 69 years and 67 patients aged ≥70 years. The majority developed severe toxicities; the most common were febrile neutropenia, gastrointestinal, infections, and cardiovascular. Older patients were at higher risk for grade ≥3 cardiovascular toxicities (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.25-5.00; P < .001) and skin toxicities (HR, 2.45; 95% CI, 1.08-5.54, P = .032). In the older group, nonrelapse mortality at 100 days and at 2 years was 2.99% (95% CI, 0.55-9.32) and 6.2% (95% CI, 1.97-13.95), respectively, vs 1.79% (95% CI, 0.68-3.92) and 2.91% (95% CI, 1.37-5.42), respectively, in the younger group. When adjusting for the number of grade ≥3 toxicities within the first 100 days, older patients had a 1.71-fold (95% CI, 1.08-2.71) increased risk for progression or death relative to younger patients. Although BEAM followed by AHCT is effective, it is associated with significant organ toxicities, especially in patients aged ≥70 years. Interventions to mitigate toxicities while maintaining efficacy are much needed., (© 2021 by The American Society of Hematology.)

T cell-depleted (TCD) allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for hematologic malignancies in adults, shown to reduce graft-versus-host disease (GVHD) without increased relapse. We retrospectively reviewed a single-center, 11-year experience of 214 patients aged ≥ 55 years to determine tolerability and efficacy in the older adult. Most patients (70%) had myeloid diseases, and most acute leukemias were in remission. Median age was 61 years, with related and unrelated donors ≥8/10 HLA matched. Hematopoietic cell transplantation-specific comorbidity index scores were intermediate and high for 84%. Conditioning regimens were all myeloablative. Grafts were peripheral blood stem cells (97%) containing CD3 dose ≤10 3-4 /kg body weight, without pharmacologic GVHD prophylaxis. With median follow-up of 70 months among survivors, Kaplan-Meier estimates of overall and relapse-free survival were 44% and 41%, respectively (4 years). Cumulative incidence of nonrelapse mortality at day +100 was only 10%. Incidence of GVHD for acute (grades II to IV) was 9% at day +100 and for chronic was 7% at 2 and 4 years (8 extensive, 1 overlap). Median Karnofsky performance status for patients > 2 years post-transplant was 90%. As 1 of the largest reports for patients ≥2 aged ≥55 years receiving TCD HSCTs, it demonstrates curative therapy with minimal GVHD, similar to that observed in a younger population., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: It is not clear which educational strategy is most effective in helping patients to change their lifestyles. This study compared the efficacy of two different educational models on reducing blood pressure (BP)., Methods: This was a randomized controlled trial in ambulatory hypertensive patients >65 years of age. Workshops that aimed to develop self-management and patient empowerment (PEM) were compared to workshops that used a compliance-based model (CEM). The primary outcome was change in systolic BP at 3 months compared with basal values between groups (net reduction), measured by 24-h ambulatory BP monitoring., Results: A total of 30 patients were educated with PEM and 30 others with CM. Both groups were statistically similar with regard to age (67 v 70 years), systolic BP (157 v 156 mm Hg) and diastolic BP (88 v 88 mm Hg), diabetes (23% v 31%), and basal natriuresis 116 v 121 mEq/day). There were more women in the PEM group (57% v 30%). The PEM group showed a significant reduction of 8 mm Hg (95% confidence interval [CI] 2 to 15), whereas the CM group showed a reduction of 3 mm Hg (95% CI -3 to 8), with a net reduction of 6 (95% CI -3 to 14). Mean net night-time systolic BP reduction was 12 mm Hg (95% CI 2 to 22). BP control was 70% in PEM group vs 45% in CM group (P = 0.045). The relative odds ratio for BP control for the PEM group after adjustment for age, sex, diabetes, basal blood pressure and changes in pharmacological treatment was 3.7 (95% CI 1.05 to 13.1)., Conclusion: Based on these study results, the self-management education model was significantly more effective than the compliance-based model in BP control.