Hematopoietic cell transplantation from haploidentical donors (haploHCT) has facilitated treatment of AML and MDS by increasing donor availability and became more feasible since the introduction of post-transplant cyclophosphamide (ptCY). In our single-center retrospective analysis including 213 patients with AML or MDS, we compare the outcome of haploHCT (n = 40) with ptCY with HCT from HLA-identical MRD (n = 105) and MUD (n = 68). At 2 years after transplantation, overall survival (OS) after haploHCT was not significantly different (0.59; 95% confidence interval 0.44-0.79) compared to MRD (0.77; 0.67-0.88) and MUD transplantation (0.72; 0.64-0.82, p = 0.51). While progression-free survival (PFS) was also not significantly different (haploHCT: 0.60; 0.46-0.78, MRD: 0.55; 0.44-0.69, MUD: 0.64; 0.55-0.74, p = 0.64), non-relapse mortality (NRM) was significantly higher after haploHCT (0.18; 0.08-0.33) vs. MRD (0.029; 0.005-0.09) and MUD (0.06; 0.02-0.12, p < 0.05). Higher NRM was mainly caused by a higher rate of fatal infections, while deaths related to GvHD or other non-relapse reasons were rare in all groups. As most fatal infections occurred early and were bacterial related, one potential risk factor among many was identified in the significantly longer time to neutrophil engraftment after haploHCT with a median of 16 days (interquartile range; 14.8-20.0) vs. 12 days (10.0-13.0) for MRD and 11 days (10.0-13.0) for MUD (p = 0.01).
Ce highlight en hématologie a été rédigé par des hématologues provenant de la Suisse entière, et se veut refléter un travail commun de la Société Suisse d'Hématologie.Les chapitres se déclinent sur les activités et maladies principales prises en charge par les intervenantes et intervenants de la spécialité.
Transthyretin amyloidosis (ATTR amyloidosis) is a disease caused by deposition of transthyretin fibrils in organs and tissues, which causes their dysfunction. The clinical heterogeneity of ATTR amyloidosis and the variable presentation of symptoms at early disease stages, historically meant treatment delays. Diagnostic tools and therapy options of ATTR amyloidosis have markedly improved in recent years. The first Swiss Amyloidosis Network (SAN) meeting (Zurich, Switzerland, January 2020) aimed to define a consensus statement regarding the diagnostic work-up and treatment for systemic amyloidosis, tailored to the Swiss healthcare system. A consortium of 45 clinicians and researchers from all Swiss regions and universities was selected by the SAN committee to represent all sub-specialty groups involved in care of patients with amyloidosis. A steering committee conducted the literature search and analysis, wrote the critical synthesis and elaborated a list of statements that were evaluated by all the participants. These recommendations will improve outcomes and quality of life for patients with ATTR amyloidosis. A global review of these guidelines is planned every 3 years with a formal meeting of all the involved experts.
Systemic amyloidoses are chronic diseases with important consequences for patients' quality of life, thus presenting a major medical and socioeconomic burden. This article discusses the current diagnostic challenges and therapy options for systemic amyloidosis and summarizes the activities of the Swiss Amyloidosis Network (SAN) which aims to increase awareness of these rare diseases, include patients in the Swiss Amyloidosis Registry for research purposes and develop interdisciplinary guidelines for diagnosis and therapy of systemic amyloidosis in Switzerland.
Abstract Daratumumab, an anti‐CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%‐40%), and the median difference between involved and noninvolved free light‐chains (dFLC) was 446 mg/L (range 102‐1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7‐28 days), and the median time to best hematological response was 64 days (range 7‐301 days). The hematological overall response was 90%, with high‐quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7‐9.1). Infusion‐related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow‐up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function.
Die Hämatologie ist ein Fachgebiet, das sich sowohl im Laborbereich als auch bei der klinischen Behandlung von Patientinnen und Patienten stark entwickelt. Teil 1 einer Übersicht der jüngsten Entwicklungen.
Die Hämatologie ist ein Fachgebiet, das sich sowohl im Laborbereich als auch bei der klinischen Behandlung von Patientinnen und Patienten stark entwickelt. Teil 2 einer Übersicht der jüngsten Entwicklungen.
AIMS OF THE STUDY: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005–2014 and prospectively from 2015 onwards. METHODS: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. RESULTS: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33–4.87); it was 4.87 years (95% CI 3.14–7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48–3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4–95.3%), 68.5% (95% CI 57.4–81.7%) and 66.0% (95% CI 54.6–79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2–99.8%), 77.0% (95% CI 63.4–93.7%) and 50.6% (95% CI 31.8–80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). CONCLUSION: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.
