Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis. Methods We conducted a phase 3 open-label, controlled trial to assess the efficacy and safety of pegcetacoplan as compared with eculizumab in adults with PNH and hemoglobin levels lower than 10.5 g per deciliter despite eculizumab therapy. After a 4-week run-in phase in which all patients received pegcetacoplan plus eculizumab, we randomly assigned patients to subcutaneous pegcetacoplan monotherapy (41 patients) or intravenous eculizumab (39 patients). The primary end point was the mean change in hemoglobin level from baseline to week 16. Additional clinical and hematologic markers of hemolysis and safety were assessed. Results Pegcetacoplan was superior to eculizumab with respect to the change in hemoglobin level from baseline to week 16, with an adjusted (least squares) mean difference of 3.84 g per deciliter (P Conclusions Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis. (Funded by Apellis Pharmaceuticals; PEGASUS ClinicalTrials.gov, NCT03500549. opens in new tab.

Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe

Subsequent neoplasms (SNs) compromise long-term survivors after hematopoietic cell transplantation. We performed a retrospective analysis of SNs in 10 358 recipients of umbilical cord blood transplantation (UCBT) from 1988 to 2018. SNs developed in 233 patients and 84 were of pediatric age. Indications for UCBT were malignant hematological diseases in 199 patients (85%). Three groups of SNs were observed. Posttransplant lymphoproliferative disorders (PTLD) were reported in 145 patients in a median of 4 months after UCBT. Of these, 9 patients died from relapse, 83 from PTLD, and 24 from transplant-related causes. At last follow-up, 29 were alive; 5-year overall survival (OS) after PTLD diagnosis was 21%. Acute leukemia/myelodysplasia (AL/MDS) was diagnosed in 23 patients in a median of 28 months after UCBT and included 3 donor-cell AL. Four of 23 patients died from relapse of primary disease, 8 from progression of SNs, and 4 from TRM. Seven patients remain alive; the 5-year OS after AL/MDS diagnosis was 36%. Solid tumors (ST) were reported in 65 patients in a median of 54 months after UCBT. Most common tumor sites were lung, thyroid, bone, and soft tissue. A total of 33 patients died (26 owing to ST, 6 to relapse of primary disease, and 1 cause missing). At last follow-up, 32 of 65 patients were alive; the 5-year OS after the diagnosis of ST was 51%. In conclusion, despite their poor outcomes, SNs that occur after UCBT are extremely rare. Identification of risk factors and early detection may help to improve OS

Adaptation française et analyse des qualités psychométriques du questionnaire d’évitement et de fusion (AFQ) dans une population adulte

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New therapeutic strategies for invasive aspergillosis in the era of azole resistance: how should the prevalence of azole resistance be defined?

International audienceGiven reports showing a high prevalence of azole resistance in Aspergillus fumigatus, alternatives to azole therapy are discussed when a threshold of 10% of azole-resistant environmental isolates is reached. This raises the issue of calculation of this threshold, either on the prevalence of azole-resistant isolates as a whole or on the prevalence of azole-resistant cases in populations at risk of invasive aspergillosis (IA). For isolate evaluation, there are high disparities in routine microbiological procedures for the isolation of A. fumigatus and azole resistance detection. There are also huge differences between the microbiological work-up for diagnosing IA. Some centres rely on galactomannan detection alone without actively trying to culture appropriate samples, which affects reliability of the figures on the prevalence of resistance and thus the threshold of resistance. Moreover, reports from the laboratory could mix up figures from completely different patient populations: frequent azole-resistant isolates from pneumology patients and rare azole-resistant isolates from haematology patients. Therefore, to sum isolates from different specimens and different wards can lead to erroneous calculations for the restricted populations at risk of developing IA. In conclusion, assessing the incidence of azole resistance in A. fumigatus should be based on harmonized consensual microbiological methods and reports should be restricted to IA episodes in identified populations at risk of IA when the issue is to define an operational threshold for modifying recommendations

The Prospective Effects of Coping Strategies on Mental Health and Resilience at Five Months after HSCT

International audienceObjectives: Hematopoietic stem cell transplantation (HSCT) is a stressful event that engenders psychological distress. This study examines the prospective effects of coping strategies during hospitalization on resilience and on various mental-health dimensions at five months after transplantation. Methods. One hundred and seventy patients (Mage = 52.24, SD = 13.25) completed a questionnaire assessing adjustment strategies during hospitalization, and 91 filled out a questionnaire five months after HSCT (Mage = 51.61, SD = 12.93). Results: Multiple regression analyses showed that a fighting spirit strategy positively predicted resilience (p < 0.05), whereas anxious preoccupations predicted anxiety (p < 0.05), poorer mental QoL (p < 0.01), and were associated with an increased risk of developing PTSD (OR = 3.27, p < 0.01; 95% CI: 1.36, 7.84) at five months after transplantation. Hopelessness, avoidance, and denial coping strategies were not predictive of any of the mental health outcomes. Finally, the number of transplantations was negatively related to a fighting spirit (p < 0.01) and positively related to hopelessness-helplessness (p < 0.001): Conclusions: These results highlight the importance of developing psychological interventions focused on coping to alleviate the negative psychological consequences of HSCT

Mindful Non-judging and Experiential Avoidance Before Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) are Associated to Post-traumatic Stress Disorder (PTSD) Symptomatology 5 Months Later

International audienceAbstract Objectives Hematopoietic stem cell transplantation (HSCT) can be a traumatic experience for the patient, engendering psychological distress and sometimes post-traumatic stress disorder (PTSD). The aim of this study was to explore the relations between psychological resources (i.e., dispositional mindfulness, optimism, and acceptance) and deleterious factors (i.e., experiential avoidance and alexithymia) assessed before HSCT on PTSD symptomatology 5 months after transplantation. The relations between symptoms of PTSD and the five facets of dispositional mindfulness were also explored. Methods Among the 187 patients who completed the first questionnaire measuring dispositional factors (i.e., dispositional mindfulness, acceptance, optimism, experiential avoidance, and alexithymia) prior to hospitalization, 91 patients were assessed at 5 months after HSCT on PTSD symptomatology. Various medical and mental health variables were controlled.Results Acceptance, experiential avoidance, and the non-judging facet of mindfulness correlated significantly with PTSD symptoms at 5months. Adjusting for major comorbid psychiatric disorders of PTSD (i.e., anxiety and depression), only expe-riential avoidance and mindful non-judging remained significant correlates of PTSD symptomatology. In addition, controlling for the same comorbidities, a binary logistic regression analysis revealed that only the non-judging facet of mindfulness is related to a lower risk of developing symptoms of PTSD (OR = 0.38, p < .01; 95% CI: 0.16, 0.95).Conclusions This study highlights the importance of psychological constructs barely explored in HSCT. Cultivating a state of non-judgment and non-avoidance of internal experiences is negatively associated to PTSD symptoms following HSCT

Retrospective and prospective measures of post-traumatic growth reflect different processes: longitudinal evidence of greater decline than growth following a hematopoietic stem-cell transplantation

International audienceAbstract Background This prospective longitudinal study examined and compared two measures (prospective and retrospective ones) of post-traumatic growth (PTG) following Hematopoietic Stem-Cell Transplantation (HSCT) and their respective relationships with mental health and psychological disposition. We also tested the hypothesis that unwillingness to be in contact with distressing thoughts and feelings—i.e. experiential avoidance—would moderate the relationship between Post-Traumatic Stress Disorder (PTSD) and growth. Methods This study was carried out with 187 patients. Patients completed the Post-Traumatic Growth Inventory (PTGI) 5 months after HSCT and scales tapping into the five domains of PTGI during hospitalisation and 5 months after HSCT. Mental health and psychological disposition were also assessed prior to hospitalisation. A PTSD scale was administered at the five-month follow-up. Results Prospective and retrospective measures of PTG were weakly correlated. Bayesian pre/post-HSCT comparisons in the prospective measure of PTG revealed substantial to very strong decline in four of the five dimensions assessed. Overall, RCI indicated a reliable increase for 5.6% of patients and a reliable decrease for 40.8% of patients. Confirming that retrospective and prospective measures of PTG reflect different processes, they were not related to the same mental health and psychological disposition variables. Moreover, the hypothesis that acquiring positive outcomes from a potentially traumatic experience, such as HSCT, requires direct confrontation with the source of distress was supported in the case of the retrospective measure of growth but not in the case of the prospective measure growth. Conclusions Retrospective measures such as the PTGI do not appear to assess actual pre- to post-HSCT change. HSCT seems more linked to psychological decline than to growth

Mental health and quality of life of patients undergoing hematopoietic stem cell transplantation (HSCT) prior to hospitalization: a cross-sectional complete state health study

International audienceObjectiveThe main goal of this cross-sectional study was to examine the relationships between negative/positive psychological dispositions, mental health, and quality of life (QoL) prior to hospitalization among patients undergoing hematopoietic stem cell transplantation (HSCT).MethodA total of 187 patients (Mage = 52.07 years) completed a questionnaire 19.6 days before an allograft. Several positive psychological dispositions (i.e. mindfulness, optimism, and acceptance) and a negative psychological disposition (i.e. experiential avoidance) were assessed. Our dependent variables were mental health (i.e. happiness, depression, and anxiety) and QoL.ResultsIn the sample, 56.8% of patients were characterized by an impaired QoL and 56.9% and 21% had, respectively, anxiety and depression levels above the critical threshold (i.e. a score above seven on the Hospital Anxiety and Depression Scale). Anxiety, depression, and happiness were significantly related to the mental component of QoL, whereas physical QoL was only related to depression and happiness. Providing additional support for a complete state health approach, several positive and negative psychological dispositions (i.e. optimism, acceptance, and experiential avoidance) were robustly related to mental illness/wellness and QoL.ConclusionsThese results highlight the importance of improving psychological health and QoL among HSCT patients prior to hospitalization by both promoting positive psychological and health factors and alleviating negative ones

Protective and deleterious sociopsychological factors involved in the mental health of patients prior to hospitalization for hematopoietic stem cell transplantation

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Psychological adjustment during hospitalization of patients undergoing hematopoietic stem cell transplantation (HSCT): The role of transactional processes and sociopsychological variables

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