Clinicians’ perspectives on supporting individuals with severe anorexia nervosa in specialist eating disorder intensive treatment settings

Background Admissions to intensive treatment (i.e., inpatient [IP] and/or day patient [DP]) for individuals with severe anorexia nervosa (AN) are common. Growing literature indicates potential risks and benefits of each intensive treatment approach; however, existing research has focused on patient and carer perspectives of these treatments. Also, there is scant empirical evidence available for guiding the parameters of intensive treatments for AN. We therefore explored clinicians’ perspectives and experience of supporting adults with severe AN in intensive settings. Methods We conducted twenty one semi-structured interviews with clinicians who deliver intensive treatments (i.e., IP and/or DP) for individuals with severe AN across four specialist Eating Disorder Services in the United Kingdom between May 2020 and June 2021. We asked clinicians about their views and experiences of supporting individuals with severe AN in intensive treatment settings and the challenges and opportunities associated with IP and DP treatment. Data were analysed using reflexive thematic analysis supported by NVivo software. Results Five broad and interrelated themes were identified: (1) Intensive Support; (2) The Severity of Patients’ Illnesses; (3) Hope and Recovery; (4) Which Treatment When; (5) Limited Resources; and (6) Carer Burden. We identified various similarities between the two intensive treatment approaches, including the value of intensive and multidisciplinary support and carer involvement, and the challenge of managing complex and unique needs in resource-limited intensive settings. We also found differences in the relationship of treatment to patients’ home environments, the necessity of patient motivation, and the management of risk. Conclusions Both intensive treatment settings are valued by clinicians; however, there are unique challenges and opportunities for supporting individuals with severe AN within each. Our findings suggest DP treatment may be used as an alternative to IP treatment for individuals with severe AN. However, clear questions remain over which intensive treatment setting is best suited to which patient when and should be the focus of future research.

Feasibility of Wearable-Based Remote Monitoring in Patients During Intensive Treatment for Aggressive Hematologic Malignancies

PURPOSE Intensive treatment protocols for aggressive hematologic malignancies harbor a high risk of serious clinical complications, such as infections. Current techniques of monitoring vital signs to detect such complications are cumbersome and often fail to diagnose them early. Continuous monitoring of vital signs and physical activity by means of an upper arm medical wearable allowing 24/7 streaming of such parameters may be a promising alternative. METHODS This single-arm, single-center observational trial evaluated symptom-related patient-reported outcomes and feasibility of a wearable-based remote patient monitoring. All wearable data were reviewed retrospectively and were not available to the patient or clinical staff. A total of 79 patients (54 inpatients and 25 outpatients) participated and received standard-of-care treatment for a hematologic malignancy. In addition, the wearable was continuously worn and self-managed by the patient to record multiple parameters such as heart rate, oxygen saturation, and physical activity. RESULTS Fifty-one patients (94.4%) in the inpatient cohort and 16 (64.0%) in the outpatient cohort reported gastrointestinal symptoms (diarrhea, nausea, and emesis), pain, dyspnea, or shivering in at least one visit. With the wearable, vital signs and physical activity were recorded for a total of 1,304.8 days. Recordings accounted for 78.0% (63.0-88.5; median [interquartile range]) of the potential recording time for the inpatient cohort and 84.6% (76.3-90.2) for the outpatient cohort. Adherence to the wearable was comparable in both cohorts, but decreased moderately over time during the trial. CONCLUSION A high adherence to the wearable was observed in patients on intensive treatment protocols for a hematologic malignancy who experience high symptom burden. Remote patient monitoring of vital signs and physical activity was demonstrated to be feasible and of primarily sufficient quality.

Acute accidental inhalation of Chlorine gas: A mini review

The Authors report an accidental gas exposure of Chlorine gas in a worker. This accident is very uncommon and can lead to important life-threatening conditions, such as Reactive Airway Disfunction Syndrome (RADS) and Acute Respiratory Distress Syndrome (ARDS) with important pulmonary disfunctions and even death. This syndrome results are reversible when a quick and appropriate intensive treatment is performed.

Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report

Background Isolated methylmalonic aciduria can be caused by pathogenic mutations in the gene for methylmalonyl-CoA mutase or in the genes encoding enzymes involved in the intracellular metabolism of cobalamin. Some of these mutations may be cobalamin responsive. The type of methylmalonic aciduria cannot always be assumed from clinical manifestation and the responsiveness to cobalamin has to be assessed for appropriate cobalamin administration, or to avoid unnecessary treatment. The cases presented herein highlight the importance of genetic testing in methylmalonic aciduria cases and the need for standardisation of the in vivo cobalamin-responsiveness assessment. Case presentation We describe two patients who presented in the first week of life with rapid neurological deterioration caused by metabolic acidosis with severe hyperammonaemia requiring extracorporeal elimination in addition to protein restriction, energy support, carnitine, and vitamin B12 treatment. The severity of the clinical symptoms and high methylmalonic acid concentrations in the urine (>30,000 μmol/mmol of creatinine) without hyperhomocysteinaemia in both of our patients suggested isolated methylmalonic aciduria. Based on the neonatal manifestation and the high methylmalonic acid urine levels, we assumed the cobalamin non-responsive form. The in vivo test of responsiveness to cobalamin was performed in both patients. Patient 1 was evaluated as non-responsive; thus, intensive treatment with vitamin B12 was not used. Patient 2 was responsive to cobalamin, but the dose was decreased to 1 mg i.m. every two weeks with daily oral treatment due to non-compliance. Genetic tests revealed bi-allelic mutations in the genes MMAB and MMAA in Patient 1 and 2, respectively. Based on these results, we were able to start intensive treatment with hydroxocobalamin in both patients. After the treatment intensification, there was no acute crisis requiring hospitalisation in Patient 1, and the urine methylmalonic acid levels further decreased in Patient 2. Conclusions Despite carrying out the in vivo test of responsiveness to cobalamin in both patients, only the results of molecular genetic tests led us to the correct diagnosis and enabled intensive treatment with hydroxocobalamin. The combination of the standardized in vivo test of cobalamin responsiveness and genetic testing is needed for accurate diagnosis and appropriate treatment of isolated methylmalonic aciduria.

Differences and Similarities in Treatment Paradigms and Goals Between AL Amyloidosis and Multiple Myeloma

Although there are similarities in the treatment paradigms between AL amyloidosis and multiple myeloma, there are also fundamental differences. A similarity is of course the use of anti-plasma cell drugs in both diseases; however, the most serious mistake a hemato-oncologist can make is to use the same treatment schedule in dosing and frequency in AL amyloidosis patients as in multiple myeloma patients. AL amyloidosis patients with >10% bone marrow plasma cell infiltration in particular are at risk of receiving a more intensive treatment than they can tolerate. This difference in dosing and frequency is true for many anti-clonal drugs, but it is most apparent in the use of high-dose melphalan and autologous stem cell transplantation. While in multiple myeloma in the age group of ≤70 years, more than 80% of patients are fit enough to receive this intensive treatment, this is the case in less than 20% of AL amyloidosis patients. A similarity is the alignment in the goal of treatment. Although in AL amyloidosis has long been recognized that the goal should be complete hematological remission, this has become more apparent in multiple myeloma in recent years. A common goal in the coming years will be to evaluate the role of minimal residual disease to improve survival in both diseases.

Patients with Acute Myeloid Leukemia on Non-Intensive Therapy: Applicability of the European Leukemia Net Risk Classification

BACKGROUND The revised genetic risk classification established by the European Leukemia Net (ELN) in 2017 stratifies patients diagnosed with acute myeloid leukemia (AML) into 3 prognostic categories (favourable, intermediate, and adverse) based on cytogenetic and molecular characteristics.The ELN classification is widely accepted in AML patients despite the fact that validation studies were performed in participants who received exclusively first-line treatment with intensive chemotherapy. For this reason, it is not well established whether the ELN risk groups are applicable to patients on non-intensive first-line treatment. OBJECTIVES - To describe and compare baseline characteristics at diagnosis between patients with AML treated with intensive and non-intensive therapy. - To assess whether the ELN prognostic classification is applicable in these subgroups of patients. METHODS We retrospectively analysed patients with newly diagnosed AML admitted to our center between 2007 and 2020. Patients with acute promyelocytic leukemia (M3), patients younger than 18 years old and/or patients who received exclusively supportive treatment were excluded. Demographic and clinical data, disease characteristics at diagnosis and first-line treatment were collected. Cytogenetic and molecular characteristics were used to classify patients in ELN risk groups. RESULTS Of the total of patients (n=218), one hundred and fifty-six (71.6%) received intensive chemotherapy treatment, while 62 (28.4%) were treated with non-intensive strategies. Idarubicin and cytarabine based schemes regimens (IA) were administered in most patients (98.6%) who received intensive treatment while the rest received fludarabine based regimens. One patient (0.6%) was treated with danurubicin and cytarabine liposome (CPX-351). Fifty-four (87%) patients treated with non-intensive regimens received hypomethylating agents, mostly azacitidine. Five patients (8%) were treated with venetoclax in combination with a hypomethylating agent. Table 1 shows the characteristics at diagnosis in both groups of patients. Patients who received intensive chemotherapy were younger and had higher leukocyte count, LDH values and a higher percentage of blasts in peripheral blood and bone marrow with a median of 40% and 62% blasts respectively. On the other hand, patients under non-intensive treatment more frequently presented a past history of hemopathy and a higher percentage of bone marrow dysplasia. Regarding ELN stratification significant differences were found between both groups. Patients who received aggressive chemotherapy vs patients who did not, were classified in low (28% vs. 7%), intermediate (36% vs. 58%) and high risk (36% vs. 35%) respectively (Figure 1). At the end of the follow-up, 41% of the patients who had received intensive therapy were alive while only 6.5% of the patients who had received non-intensive treatment were alive. Significant differences in survival were observed between both groups (p<0.01); with 1-year overall survival (OS) of 65.8% for intensive therapy group and 49.6% for non-intensive therapy group. In the intensive chemotherapy group, significant differences in survival were observed according to ELN risk stratification (p<0.01), with 5-year OS of 55%, 29% and 23.9% for low, intermediate and high-risk groups respectively. For low-risk patients, median OS was not reached while it was 20 months for the intermediate risk group and 12.2 months for the high-risk group. However, in patients receiving non-intensive therapies, there were no significant differences in survival among different prognostic categories (p=0.06). In this group, 1-year OS was 25%, 57.6% and 40.7% and median OS was 2.1, 14.8 and 10.1 months for low, intermediate and high-risk groups respectively. See Figure 2. CONCLUSIONS: As validated in previous trials, ELN classification constitutes an adequate prognostic marker for patients with newly diagnosed AML treated with intensive chemotherapy. In our series, this classification does not appear to be a good predictor of survival for patients diagnosed with AML who initiated non-intensive treatments. Further validation in prospective studies are needed to better classify this growing subgroup of patients in clinical practice. Figure 1 Figure 1. Disclosures Martín-Rojas: Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Font Lopez: Pfizer: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees; CELGENE-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria.

Characteristics and Outcome of Elderly Patients (> 55 Years) with Acute Lymphoblastic Leukemia (ALL)

Introduction: Prognosis of elderly ALL patients is generally considered to be poor. Nonetheless, data on disease characteristics, treatment and outcome of this group of patients is scarce. Methods: Between May 2003 and October 2020, 96 patients (pts) aged > 55 years with B-precursor ALL (91 pts) or T-ALL (5 pts), received first-line induction chemotherapy (84 pts) or were admitted for salvage treatment (8 pts) or allogeneic stem cell transplantation (alloSCT, 4 pts) at the University Hospital Muenster, Germany. 78 patients were diagnosed with a common-ALL (27 pts were BCR/ABL positive) and 13 patients with a pro-B-ALL. Age adapted BFM (Berlin-Frankfurt-Muenster)-like treatment regimens, according to the recommendations of the GMALL (German multicenter ALL study group) for younger (18-55 years, 25 pts) or elderly patients (> 55 years, 68 pts) were used. In general, these protocols consisted of two cycles of induction therapy followed by consolidation, reinduction and consolidation therapy blocks in the 1 st year as well as a consecutive maintenance therapy in the 2 nd year. 3 patients (3%) received no intensive treatment due to poor performance status and comorbidities. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank-test and Cox proportional hazards model for RFS and OS, respectively. Results: Median patient age at diagnosis was 66 years (range 55-89 years). 94% of all patients had an ECOG (Eastern Cooperative Oncology Group) status of 0-2 and 92% had a Charlson comorbidity index of 0-2. The median follow-up of all patients was 2.0 years (range 20 days - 16.9 years) and of surviving patients 3.7 years (range 8.8 months - 16.9 years). A complete remission (CR) after induction therapy was documented in 62 of 81 (77%) patients receiving their initial induction therapy at our center. Minimal residual disease (MRD) status was analyzed by quantitative real time PCR in 44 of these patients and 19 patients had an MRD negative CR (43%) after induction therapy. The rate of early death after intensive therapy (death within 100 days after start of treatment) was 6%. The 3 patients not treated with intensive chemotherapy died within 3 months. 27 of 93 patients finished the first year of treatment. Subsequent maintenance therapy was administered to 12 patients. The reasons for discontinuation of conventional treatment in the first and second year were relapsed disease (31 pts), alloSCT in 1 st CR (23 pts), toxicity/patients' preference (17 pts) and death in CR under conventional therapy (7 pts). 3 patients have not completed their therapy yet. OS and RFS of the entire cohort at 1 year were 73% (95% CI: 64-82%) and 57% (95% CI: 47-67%) and at 3 years 46% (95% CI: 36-56%) and 32% (95% CI: 22-42%), respectively. The cumulative incidence of relapse at 1 and 3 years was 29% (95% CI: 20-41%) and 56% (95% CI: 45-69%), respectively. OS of those patients receiving an alloSCT (23 pts in 1 st CR, 7 pts in 2 nd CR, 3 pts with active disease, median age at alloSCT 62 years) at 1 and 3 years was 82% (95% CI: 68-95%) and 49% (95% CI: 32-67%), respectively. The cumulative incidence of relapse after alloSCT at 1 and 3 years was 16% (95% CI: 7-35%) and 32% (95% CI: 18-56%), respectively. Regarding the entire patient cohort, older age (> 75 years, 15 pts) was significantly associated with an inferior OS (p < .001). BCR/ABL status, ALL phenotype (T- or B-ALL) or intensity of conventional treatment applied (protocol originally intended for patients ≤ 55 years vs > 55 years) had no significant impact on OS. In multivariate analysis, ECOG status >2 and persisting disease after 1 st consolidation therapy were risk factor associated with inferior OS (p < .05). Conclusion: Intensive treatment is feasible in selected elderly ALL patients (> 55 years). High relapse rates and impaired survival rates underline the need for novel therapeutic strategies. Disclosures Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Brüggemann: Incyte: Other: Advisory Board; Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stelljes: Celgene/BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau.