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In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 8 ( 2021-08), p. 2332-2345

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-01117-w

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2

In: mBio, American Society for Microbiology, Vol. 5, No. 6 ( 2014-12-31)

Abstract: Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year, including an outbreak of 18 cases over 8 weeks. Whole-genome sequencing (WGS) was used to analyze recent and historical isolates and to design a clade-specific genotyping method that uncovered a clone associated with the outbreak, thus allowing a case-case study to analyze the risk factors associated with infection by the clone. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen.

Type of Medium: Online Resource

ISSN: 2161-2129 , 2150-7511

URL: Article

DOI: 10.1128/mBio.02309-14

Language: English

Publisher: American Society for Microbiology

Publication Date: 2014

detail.hit.zdb_id: 2557172-2

In: British Journal of Haematology, Wiley, Vol. 153, No. 1 ( 2011-04), p. 58-65

Type of Medium: Online Resource

ISSN: 0007-1048

URL: Issue

URL: Article

DOI: 10.1111/bjh.2011.153.issue-1

DOI: 10.1111/j.1365-2141.2011.08588.x

Language: English

Publisher: Wiley

Publication Date: 2011

detail.hit.zdb_id: 1475751-5

In: The Lancet Haematology, Elsevier BV, Vol. 2, No. 3 ( 2015-03), p. e108-e117

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(15)00020-4

Language: English

Publisher: Elsevier BV

Publication Date: 2015

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3708-3708

Abstract: Background: Prognosis of relapsed/refractory acute lymphoblastic leukemia (ALL) in adults is dismal. CD22 is highly expressed in patients with B-ALL. Epratuzumab (hLL2) is a humanized monoclonal antibody targeting CD22 surface antigen. We performed a standard 3+3 phase 1 study to assess the feasibility, tolerability, and efficacy of a 90yttrium-labeled anti-CD22 epratuzumab tetraxetan (90Y-DOTA-hLL2) radioimmunotherapy (RIT) in adults with refractory/relapsed CD22+ B-ALL. Methods: After premedication with corticosteroid, 90Y-DOTA-hLL2 was administered twice on days 1 and 8 (+2), successively at 2.5 (level 1), 5.0 (level 2), 7.5 (level 3), and 10.0 (level 4) mCi/m². The first two patients also received 4 infusions of DOTA-hLL2 360 mg/m²/day before the RIT. This “cold phase” was terminated after observing no efficacy and full saturation of the CD22 target on the leukemic cells. Minimal residual disease (MRD) was assessed either by flow cytometry or by RQ-PCR for BCR-ABL1 analyses in Philadelphia chromosome positive (Ph+) B-ALL patients. Dose-limiting toxicity (DLT) was defined as any non-reversible grade 〉 3 non-hematological toxicity or grade 4 pancytopenia with hypocellular bone marrow lasting for 〉 6 weeks. Maximum tolerated dose (MTD) was defined as the dose level at which 2 of 3 or 2 of 6 patients experienced a DLT. Dosimetry, organ distribution and elimination of the radiotracer were studied between the two RIT infusions in all but one patient, using whole-body scintigraphy recorded after 111Indium-epratuzumab tetraxetan injection and blood pharmacokinetics. Patients were evaluated for response between 4 and 6 weeks following the first infusion of RIT. Findings: Between October 2011 and June 2014, 20 patients were enrolled. Three patients were not considered for analyses because of disease progression (n=2) or persistent non-blastic pancytopenia (n=1) before RIT. Overall, 17 cases were treated (5 at level 1 including 2 previously treated with the cold phase, 3 at level 2, 3 at level 3, and 6 at level 4). There were 10 males and 7 females with a median age of 62 years (range: 27-77). Two patients had primary refractory B-ALL; 10, 3 and 2 were in first, second or third relapse, respectively. Median percentage of blasts in the bone marrow was 75%. Karyotypes were as follows: Ph+ B-ALL n=6, complex n=3, MLL rearrangement n=1, hyperdiploidy n=1, hypodiploidy n=1, near-triploidy n=1, del4q (+ikaros mutation) n=1, normal (but ikaros mutation) n=1, and unknown n=2. Four patients were previously allotransplanted. Median interval between diagnosis and RIT was 16.5 months. Five patients presented immediate infusion reactions (3 grade 1, 1 grade 2 and 1 grade 3 in a patient with a previous history of severe allergic reactions) after the first RIT infusion, but received the second infusions without toxicities. All examined patients showed expected uptake of the radiotracer on potential disease sites (blood, spleen, liver, and bone marrow). No response was seen at levels 1 and 3. One molecular complete response was documented at level 2 (54-year old woman in third relapse of Ph+ B-ALL). At level 4, 2 patients achieved complete remissions (1 Ph+ ALL and 1 Ph- ALL), while all 6 cases presented with grade 4 hematologic toxicity. One DLT was documented at level 4 (non-blastic pancytopenia lasting 8 weeks), but MTD was not reached. Two patients in response received a second RIT cycle. Currently, only one non-responder is alive, while 2 of 3 responders are alive. One relapsed at 1 year and died of progression (level 2), while the two remaining are in persistent CR at 6 months post RIT, with low positive MRD. Interpretation: 90Y-DOTA-hLL2 RIT is well-tolerated and induced complete remissions even in heavily pre-treated CD22+ relapsed/refractory B-ALL patients, thus appearing to be a promising targeted therapy for CD22+ B-ALL. We recommend the dose of 10 mCi/m² given twice, one week apart/cycle, for phase 2 studies. The trial is registered at http://clinicaltrials.gov/ct no.NCT01354457. Funding: Immunomedics, Inc. Disclosures Goldenberg: immunomedics: Employment. Wegener:immunomedics: Employment.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.3708.3708

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 306-306

Abstract: L-asparaginase has been a mainstay of ALL treatment since decades and its efficacy has been demonstrated in a broad range of patient’s profiles. However its use has been hampered by frequent and/or significant toxicities, of which allergic reactions take a prominent place. In addition, loss of enzymatic efficacy, the so called “silent inactivation” may be observed as a consequence of the production of symptom-free serum antibodies directed to the asparaginase moiety and blocking its pharmacological activity. L-asparaginase loaded into homologous red blood cells (GRASPA) has been proposed as a new approach to maintain the complete activity of L-asparaginase while reducing its antibody mediated tolerability. In GRASPA, the red blood cells (RBC) act as a microbioreactor and protect the enzyme against circulating antibodies. Plasmatic asparagine diffuses through the RBC membrane to the intra cellular compartment where it is cleaved by the entrapped L-asparaginase. In addition encapsulation into RBC has been shown to extend the duration of action of drugs allowing a reduction in the number of injections. GRASPALL 2005–01 is a randomized, active controlled, dose comparison study whose first objective is to assess the efficacy (defined as asparagine depletion ≤ 2μMol/L) of 3 doses of GRASPA given in double blind, during salvage therapy in children and adults with relapsed ALL. Patients who experienced severe allergy to L-asparaginase during the first line chemotherapy were excluded from the study.Twenty-four patients from 13 French centers, including 12 children (mean age, 8 years; range, 5–17) and 12 adults (mean age, 29 years; range, 19– 47) entered the trial from February 2006 to April 2008. Patients were randomized between either native E. Coli L-asparaginase (8 ×10 000 IU/m2/infusion) or GRASPA 50, 100 or 150 IU/kg (one single infusion).The backbone chemotherapy was based on the COPRALL protocol, a FRALLE and EORTC joint protocol for relapse. The results regarding the efficacy and safety of GRASPA therapy are reported herein. The mean time of asparagine depletion ranged from 6 to 11.3 days, 6.2 to 11.9 days, and 14.6 to 22.5 days in the GRASPA 50, 100 and 150 IU/kg groups, respectively. For one patient receiving GRASPA 150UI/kg, the depletion exceeded 40 days. Overall, the mean duration of depletion and the proportion of patients with effective depletion over time with only one single infusion of GRASPA at a dose of 150 UI/kg was similar to what was observed with 8 infusions of native E. Coli asparaginase at a dose of 10 000 IU/ m2. Treatment withdrawals during the study (defined as asparagine 〉 2μMol/L at D7 of the GRASPA infusion or any safety reason preventing study treatment reintroduction) occurred in 4/6 patients (67%) in the native E. Coli asparaginase group and 5/18 patients (28%) in the GRASPA groups. Out of these, two severe allergic reactions, including one life-threatening case, one non serious allergic reaction and one severe thrombosis were observed in the native E. Coli asparaginase group. Two asparagine 〉 2μMol/L at D7 , one pancreatitis, one transient elevation of pancreatic enzymes and one pulmonary aspergillosis were reported in the GRASPA group. GRASPA is an effective therapy for depleting asparagine from the serum in children and adults with relapsed ALL. One single infusion of 150 IU/kg yielded to achieve a sustained depletion comparable with that observed with standard L-asparaginase therapy, but with a much better safety profile, especially regarding occurrence of allergic reactions, suggesting a better application of the therapeutic schedule. These results warrant future studies in allergic patients. [NCT00723346]

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.306.306

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1444-1444

Abstract: Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We therefore conducted this single arm prospective phase I/II multicenter trial (NCT02928523) to evaluate the use of a FMT-based drug in association with AML induction treatment to restore the gut microbiota diversity. Patients and methods. A total of 62 consecutive patients aged between 24 and 69 years old with a diagnosis of de novo AML were screened in 7 French sites. At time of admission and AML diagnosis (Step 1=S1), patients' faeces were collected, rigorously screened, prepared following a standardized process, and stored at -80°C until later administration. The drug was administered as an enema after hematopoietic recovery (S2) and before consolidation chemotherapy (Conso). The primary endpoint was the recovery of at least 70% of microbiota diversity (based on the Simpson index) after drug administration and the reduction of multidrug resistant bacteria carriage. Blood and feces samples were collected at S1, S2, and around 10 days post-FMT before Conso (S3). Microbiome diversity restoration was assessed by metagenomics analysis through Illumina HiSeq shotgun sequencing. Antibiotic resistance gene carriage (ARGC, also known as resistome) was evaluated through mapping of readouts on the MEGARES database. Secondary objectives included safety and analysis of host response with assessment of blood and fecal markers by ELISA and Luminex. Results. Overall, 25 patients were actually treated with FMT, and 20 were included in the per-protocol population. Induction Chemotherapy (IC) induced a dramatic shift in microbial communities, with a significant 42.3% decrease of mean α-diversity Simpson index between S1 and S2 at species level (0.85 to 0.50; p 〈 0.001). Ten days after FMT administration (S3), the Simpson index returned to its initial baseline level (0.50 to 0.86; p 〈 0.001). In addition to variations of the diversity, we demonstrated using the Bray-Curtis dissimilarity index (BC) a profound shift in the microbial communities following IC (mean BC S1-S2: 0.76) and the restoration of the initial microbial profile after FMT (mean BC S1-S3: 0.40). Moreover, IC and associated antibiotic treatments induced a significant increase in the mean number of readouts mapped against antibioresistance genes at S2 (167546 to 371466 reads, p 〈 0.01) that reflect ARGC. Then, a significant reduction of 43% of the mean number of reads mapped was observed at S3 after FMT (211128 reads, p 〈 0.001). No serious adverse events (SAE) were observed within 30 days after FMT and all post FMT SAEs were not related to the FMT procedure. Moreover, FMT did not induce any local or systemic inflammatory reaction as measured by fecal and blood markers (fecal neopterin and IgA; plasmatic CRP, IL-6 and sCD14). Interestingly, restoration of the microbiome diversity was associated with a significant reduction of CRP and fecal neopterin levels, suggesting a potential anti-inflammatory impact of FMT. Overall, FMT was well tolerated and had an excellent safety profile. The one-year overall survival estimate in the whole cohort was 84% (4 deaths among 25, none of which were related to FMT: 2 multiple organ failures, 1 heart attack and 1 grade IV resistant GVHD). The median time to death from the second FMT was 182.5 days (113-225 days). Conclusions. This is the first prospective trial testing the safety and efficacy of FMT in AML patients receiving intensive induction chemotherapy. The trial achieved its primary endpoint and established the capacity of FMT to restore a diverse microbiome with high levels of similarity to baseline, as well as reducing ARGC and intestinal inflammation. A controlled randomized trial with repeated FMT administrations is currently planned to further evaluate the impact of FMT on clinical outcomes and long-term survival. (This trial was funded by MaaT Pharma whose product was tested in this protocol). Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria. Doré:MaaT Pharma: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112825

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3710-3710

Abstract: Purpose: Best supportive care is generally offered to older patients presenting with refractory/relapsed acute lymphoblastic leukemia (ALL). There is clearly a need for new therapeutic approaches in these older patients for whom aggressive chemotherapies cannot be administered. Materials and Methods: The present study evaluated the addition of epratuzumab (hLL2), a humanized monoclonal therapeutic antibody against CD22, to the combination of vincristine and dexamethasone in older patients ( 〉 55 years) with relapsed/refractory CD22+ B-ALL. The salvage regimen consisted of epratuzumab 360 mg/m²/d iv days 1, 8, 15, and 22, vincristine 2 mg iv days 1, 8, 15 and 22, and dexamethasone 40 mg/d po days 1, 8, 15, and 22. Morphologic and phenotypic minimal residual disease (MRD) responses were determined between 4 and 6 weeks from day 1. Results: Between November 2010 and December 2013, 26 patients from six French centers were enrolled in the study. One case was excluded because of progression before receiving the treatment, while 2 younger patients were inappropriately included (49-year old female in fourth relapse and 32-year old female with refractory second relapse). Among the 25 patients considered for analyses, there were 13 males and the median age was 65 years. Eighteen, 4, 1, and 1 patients were in first, second, third, and fourth relapse, respectively, and one case had refractory B-ALL. Median percentage of blasts in bone marrow was 72%. Karyotypes were as follow: normal n=8; Ph+ n=6, complex n=1, MLL rearrangement n=1, hyperdiploidy n=2, hypodiploidy n=2, 17p duplication n=1, del9p n=1, t(1;19) n=1, t(13;14) n=1, 14 abnormality n=1. Median interval between diagnosis and salvage regimen was 16 months. Three patients were previously allotransplanted. Two patients died of progression during treatment. Salvage regimen was overall well tolerated, since the large majority of grade 3/4 toxicities were expected pancytopenia. One grade 3 toxicity was related to the first epratuzumab infusion, but the patient received the three other infusions without events. One grade 3 renal injury and one grade 4 hypertriglyceridemia of unclear etiology also were documented. The overall response rate was 40% (n=10), including 4 complete responses (CR) and 1 CR with incomplete platelet recovery (CRp) (20%), and 5 partial responses (PR) (20%). Two patients in CR/CRp were documented with negative MRD. All patients in CR/CRp and 1 patient in PR received a second cycle as consolidation. All patients died of disease progression, except two non-responder cases. Median OS was 4 months (range: 0.5-43). Median DFS for those achieving CR/CRp was 4 months (range: 1-8). Conclusion: Non-intensive chemoimmunotherapy combining vincristine/dexamethasone/epratuzumab provides encouraging results in this very high-risk, refractory/relapsed, older population. These results pave the way for integrating epratuzumab within first-line chemotherapies in older CD22+ B-ALL patients. This trial is registered at http://clinicaltrials.gov/ct no.NCT01219816. Disclosures Leguay: Gilead Sciences: Research Funding. Goldenberg:immunomedics: Employment. Wegener:immunomedics: Employment.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.3710.3710

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 31-31

Abstract: Background. Tyrosine kinase inhibitors (TKI) are standard front-line therapy for patients with BCR-ABL1/Philadelphia positive ALL (Ph+ ALL), but the relative merits of available TKIs remain uncertain. Nilotinib is a potent inhibitor of BCR-ABL1 with broader activity against ABL kinase domain mutations than imatinib and greater selectivity than dasatinib or ponatinib. As there is a paucity of data on nilotinib as first-line therapy for Ph+ ALL, the EWALL (European Working Group for Adult ALL) conducted an international clinical trial to evaluate efficacy and safety of the combination of nilotinib with low intensity chemotherapy. Patients and Methods. After a prephase with dexamethasone (DEX) and cyclophosphamide, nilotinib (400 mg BID) was given concurrently with the same chemotherapy backbone employed in the EWALL-PH01 assessing the combination with dasatinib (Rousselot et al, Blood 2016;128:774-82). Induction consisted of nilotinib combined with weekly vincristine (VCR, 1mg iv) and oral dexamethasone 40mg 2 days (20 mg over 70y). Nilotinib was continued throughout six consolidation cycles, followed by 24 months maintenance therapy with nilotinib, 6-MP, MTX and DEX/VCR boosts. Stem cell transplantation (SCT) was permitted as considered appropriate. BCR-ABL1 RTQ-PCR and kinase domain resistance mutations were centrally monitored. Primary endpoint was event-free survival (EFS) at 12 months, secondary endpoints included rates of CR, major and complete molecular response, relapse free survival (RFS), EFS and overall survival (OS). Results. 72/79 enrolled pts. were evaluable for response, 3 withdrew consent, 4 did not meet eligibility criteria. Median age was 65.5 (55-85) years, male/female ratio 0.85, ECOG status 0 or 1 in 89% of pts., median CIRS comorbidity score 5(0-19). Baseline vascular risk factors including high blood pressure (grade ≥2) were present in 36% of pts.. Sixty-eight of 72 pts. (94.4%) achieved CR, one died during induction and one was refractory, 2 pts. discontinued study therapy. Non-hematologic adverse events (AE) grades 3/4 during induction (in ≥ 5% of pts. irrespective of causality) included infections (n=20), elevated transaminases or bilirubin (n=18) and gastrointestinal AEs (n=12). The spectrum of AEs was similar during consolidation, without concerns related to cardiovascular events. 24 pts. (61y; 55-69y) underwent allogeneic (9 MUD, 12 SIB, 3 Haplo) and 3 autologous SCT. 21 pts. received reduced intensity conditioning (including 8Gy TBI, n=11) regimens. Among all pts., relapse was the main cause of treatment failure (n=23; 17 BM, 2 CNS, 3 other sites, 1 na), 11 pts. died in CR (6 after HSCT), 34 are in ongoing CR. Based on Kaplan Meier analysis, EFS (events being resistant disease, relapse or death) at 12 months was 74%, with median follow-up of 39 (24-66) months for surviving pts., EFS and OS at 4 years was 42%, and 47%, respectively. By landmark analyses using median time to HSCT as cutoff, cumulative incidence of relapse in transplanted vs. non-transplanted pts. was 32% and 47%, OS at 4 years was 61% and 39%, median OS was not reached versus 3.6 years, respectively (p=ns). The proportion of pts. with a BCR-ABL1/ABL1 ratio ≤0.1% increased from 41% after induction to 86% after consolidation 2; that of pts. with undetectable or non-quantifiable BCR-ABL1 transcripts (sensitivity ≥10-4) increased from 14% to 58%. Conclusions. Nilotinib combined with low-intensity chemotherapy is well tolerated and highly effective in elderly pts. with Ph-positive ALL. OS and EFS compare favorably with previous similar studies testing imatinib or dasatinib. With 32% of pts. undergoing allogeneic HSCT and 61% survival at 4 years, transplantation is a viable option in this elderly cohort of pts.. Disclosures Ottmann: Celgene: Consultancy, Research Funding; Novartis: Consultancy; Incyte: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Fusion Pharma: Consultancy, Research Funding. Pfeifer:Novartis: Research Funding. Cayuela:Cepheid: Other: financial sponsor to attend John Goldman Conference 2017. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Sanhes:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goekbuget:Pfizer: Consultancy, Other: Travel support, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Celgene: Consultancy; Kite / Gilead: Consultancy; Amgen: Consultancy, Other: Travel support, Research Funding. Dombret:Jazz Pharma: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Shire-Baxalta: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Cellectis: Consultancy, Honoraria, Other: Travel expenses; Otsuka: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-114552

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 1 ( 2023-01-13), p. e2250921-

Abstract: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. Objective To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. Design, Setting, and Participants This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. Exposures Disclosure of amyloid-PET result. Main Outcomes and Measures Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale–Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). Results After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30] ) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2] ; P   & amp;lt; .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00] ; P   & amp;lt; .001), IES-R intrusions (0.50 [0.13 to 0.75] vs 0.00 [0.00 to 0.25] ; P   & amp;lt; .001), and IES-R hyperarousal (0.33 [0.00 to 0.67] vs 0.00 [0.00 to 0.00] ; P   & amp;lt; .001) scores than the 78 patients who were amyloid-negative (median [IQR], age, 67 [64 to 74] years, 45 men [58%], median [IQR] education: 15 [12 to 17] years, median [IQR] MMSE score: 29 [28 to 30]). There were no observed differences between amyloid-positive and amyloid-negative patients in the median (IQR) HADS Anxiety (–1.0 [–3.0 to 1.8] vs –2.0 [–4.8 to 1.0]; P  = .06) and Depression (–1.0 [–2.0 to 0.0] vs –1.0 [–3.0 to 0.0] ; P  = .46) deltas (score after disclosure – scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = –0.43; P  = .02) whereas the presence of study partner was associated with higher disclosure-related distress ( W  = 7.5; P  = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. Conclusions and Relevance The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.

Type of Medium: Online Resource

ISSN: 2574-3805

URL: Article

DOI: 10.1001/jamanetworkopen.2022.50921

Language: English

Publisher: American Medical Association (AMA)

Publication Date: 2023

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