Data on mTOR inhibitors (mTORi) in autoimmune cytopenia (AIC), in adults are scarce. We retrospectively analysed 30 cases of refractory or relapsing AIC treated with an mTORi-based therapy. Eleven ...warm autoimmune hemolytic anaemia, 10 autoimmune thrombocytopenia, 6 acquired pure red cell aplasia, 3 autoimmune neutropenia were included. Twenty were multilineage AIC (67%) and 21 were secondary AIC (70%). mTORi were associated with other therapies in 23 AIC (77%). Twenty-two AIC (73%) responded to mTORi-based therapy: 5 reached a partial response (17%) and 17 a complete response (57%). Survival without unfavourable outcome (failure, requirement of a new therapy, or death) was longer in multilineage AIC compared to single-lineage AIC (
p
= 0.049) with a median event-free survival of 48 versus 12 months. Median event-free survival was 48 months in secondary AIC and 33 months in primary AIC (
p
= 0.79). mTORi were discontinued in 4 patients (15%) for safety reasons and in 3 patients for patient’s choice (12%). In conclusion, mTORi could be considered as an alternative or an add-on therapy in refractory or relapsing AIC in adult patients, especially in multilineage AIC.
Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of ...IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.
Point of care ultrasound (PoCUS) with pocket-size devices is an efficient and safe imaging modality that became a standard of care in various clinical settings. However, its implementation in ...hematology has never been evaluated so far. We conducted a prospective monocentric study aiming to harvest data on its usage and to assess its diagnostic and interventional performance in improving the accuracy of basic physical examination in hematological patients. After a focused training program, six hematologists were trained and conducted this study. Sixty-two patients were included. Only in 19 cases, further specialized imaging was required, whereas, in 43 patients PoCUS was sufficient to address the clinical inquiries. The use of PoCUS devices was assessed for its performance difficulty and usefulness perception with satisfactory outcomes. This study represents a proof-of-concept application of PoCUS in hematology, suggesting benefits over the physical examination.
KEY POINTS
PoCUS is particularly attractive in a hematological setting because able to improve the accuracy of physical examination.
A hematology-focused training in PoCUS using handheld devices can allow hematologists to perform bed-side diagnostic and interventional US-based exams.
Summary
Idiopathic multicentric Castleman disease (iMCD) is a non‐clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, ...reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD‐not otherwise specified (iMCD‐NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD‐NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD‐NOS, respectively. The two‐year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients.
Background
Data on plasma exchange therapy in the intensive care unit (ICU) setting are scarce. We aimed to describe the technical aspects and the adverse events associated with the procedure in ...critically ill patients.
Methods
All adult patients treated by plasma exchange in the medical ICU of the Saint‐Louis university hospital between January 1, 2013 and March 31, 2015 were prospectively included.
Results
We report on 260 plasma exchange procedures performed in 50 patients. The centrifugation technique was used for 159 (61%) procedures and the filtration technique for the other 101 (39%) procedures. Both techniques had similar efficacy to treat hyperviscosity syndrome (n = 18). Seventy (26.9%) of the 260 plasma exchange procedures were reported with at least one adverse reaction. Centrifugation and filtration techniques had similar rates of adverse reactions (23.9 vs. 31.7%, P = .19). Hypotension was the most reported (n = 21, 8%) and correlates with a low hematocrit before therapy. Most complications were related to allergic reactions to the replacement fluids. Coagulation disorders depended on the type of replacement fluid. The post‐exchange fibrinogen level was decreased by 54% 48;66 with albumin 5%, and 4% −5;17 with plasma frozen within 24 h. Twenty‐three (22.8%) of the 101 filtration procedures experienced filter clotting. Filter clotting was associated with a higher volume exchange prescribed when compared to procedures without filter clotting (4600 4000;5000 ml vs. 3900 3600;4800 ml, P < .01).
Conclusion
Plasma exchange is a relatively safe and generally well‐tolerated procedure in the ICU setting. Most adverse events are unpredictable and related to minor allergic reactions.
Purpose
Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We ...hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia.
Methods
Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed.
Results
A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype.
Conclusion
Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.
Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disease of unknown etiology. Deciphering mechanisms involved in CD pathogenesis may help improving patients’ care. Six cases ...of stereotyped sub‐diaphragmatic iMCD affecting lower limb‐draining areas and associated with severe and often ulcerative lower extremity chronic dermatological condition were identified in our cohort. Pathological examination revealed mixed or plasma‐cell type MCD. In three patients, shotgun metagenomics failed to identify any pathogen in involved lymph nodes. Antibiotics had a suspensive effect while rituximab and tocilizumab failed to improve the condition. This novel entity requires a specific approach and exclusion of potentially harmful immunomodulation.
PDF
