Immune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired ...amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow.
Herein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1). His platelet count decreased by ≤5 × 10
/l without other cytopenia. Bone marrow biopsy showed normal cellularity with a complete absence of megakaryocyte and T-CD8+ lymphocyte infiltration. Given the failure of systemic steroids, eltrombopag was started, an oral thrombopoietin receptor agonist (TPO-RA), and his platelet count subsequently increased with complete response.
Four other cases are described on literature with the same features than non-ICI-related AAT. All cases occurred after anti-PD/PD-L1 treatment with a median onset of 5 weeks. The presentation of our case is quite different with delayed cytopenia. Both ciclosporin and TPO-RA seem to be efficient therapies.
TPO-RA could be preferred in oncologic patients, but safety data are still missing to define clear guidelines for immune-related AAT management.
Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage ...activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.
Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, ...the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present.
•Ibrutinib may be associated with invasive fungal infections especially IA.•Most infections usually occur during the first months of treatment, often in patients with other risk factors for fungal infections.
Abstract
Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples ...(n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.
The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive ...infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc).
A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT.
The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample.
Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up.
With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.
Immune thrombocytopenia (ITP) is an autoimmune disease that occurs in young women. Pregnancy is a well-known risk factor for developing newly diagnosed ITP as well as for inducing disease flares in ...patients with current ITP. However, the impact of pregnancy in women with an old history of ITP, considered as cured, has not been assessed. The aim of this study was to describe the course of ITP in pregnant women with an ITP in complete remission (platelets count >100x109/L and absence of bleeding symptoms) for at least 5 years without any ITP treatment.
We retrospectively selected all pregnant women with delivery at Toulouse University Hospital, South of France, between 2010 and 2015 with a hospital discharge code of ITP (international classification of diseases; version 10 code D69.3). This code has a sensitivity of 81.2% and a positive predictive value of 89.8% in this database. All medical charts were reviewed to confirm the diagnosis of ITP. We included adult women (≥18 years) with a diagnosis of primary ITP according to French guidelines (platelet count <150 x 109 /L and exclusion of other causes of thrombocytopenia, especially other causes of thrombocytopenia during pregnancy) in complete remission for at least 5 years.
We identified 50 pregnancies in 39 ITP patients during the study period. Eleven pregnancies occurred in 10 patients in long-term complete remission of ITP at the time of pregnancy onset. Baseline characteristics were: median age at ITP diagnosis: 21 years (range: 4-29); median age at pregnancy onset:32 years (range: 26-34; history of ITP during a previous pregnancy: 1; history of bleeding: 4 (36.4%); previous treatment for ITP: 8 (72.7%), corticosteroids-CS (5), CS and intravenously immunoglobulin-IVIg (3), splenectomy (4), dapsone (1); last median platelet count before pregnancy: 170x109/L (range: 118-363).
Platelets count decreased below 100x109/L in 3 pregnancies (27.2%) from the first trimester for one patient, from the second trimester for one other and from the third trimester for the last one, with a nadir of 3, 39 and 87 (x109/L) respectively. One of them experienced a severe bleeding (grade 3 according to the International Working Group bleeding classification). All thrombocytopenic patients required treatment during pregnancy: CS+IVIg for 2 (one for bleeding and one to allow epidural analgesia) and IVIg for the other (to allow epidural analgesia). For these 3 women, the median platelet count at delivery was 128 (range: 38-159) and consequently only 2 of them could have epidural analgesia. No bleeding during delivery was observed. Transient thrombocytopenia occurred in 2 newborns.
Primary ITP considered as cured may relapse during pregnancy and may induce severe bleeding requiring specific treatment. A tight monitoring should be proposed to all pregnant women with a history of primary ITP, even after several years of complete remission.
Récher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity’s Board of Directors or advisory committees, Research Funding.
Summary
Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to ...describe ITP in this subgroup. The data source was the prospective CARMEN‐France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65–79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first‐line treatment, need of second‐line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31–17·32 and platelet count of <20 × 109/l (OR 10·05, 95% CI 4·83–67·39). Exposure to anticoagulants was strongly associated with severe bleeding (OR 7·61, 95% CI 1·77–32·83).
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