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In order to study the influence of bone marrow CD34+ cell dose on the outcome of allogeneic bone marrow transplantation (BMT), we analysed the results of BMT from HLA-identical siblings donors in 50 patients with chronic myeloid leukaemia (CML). The median numbers of nucleated cells (NC) and CD34+ cells infused were 2.18 × 108/kg (0.05–4.14 × 108/kg) and 3.12 × 106/kg (0.35–8.52 × 106/kg), respectively. All patients engrafted. In univariate analysis, there was no correlation between the number of CD34+ cells infused and the time to neutrophil recovery (P = 0.17). The Kaplan–Meier estimate of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 53 ± 14% and 2-year survival was 46 ± 15%. A number of CD34+ cells infused greater than the median was the main factor increasing survival (P = 0.0006) and decreasing 100 day transplant-related mortality (P = 0.009). Patient-, disease- and transplant-related characteristics were not statistically different among patients receiving more or less than the median number of CD34+ cells. The rate of infectious deaths was significantly higher in patients receiving less than 3.12 × 106 CD34/kg (48% vs 16%, P = 0.01). In a multivariable analysis, two factors associated with increased risk of death were advanced disease status at transplant (HR: 2.5 (95% CI: 1.09–5.75), P = 0.03) and a lower number of marrow CD34+ cells infused/kg (HR: 4.55 (95% CI: 1.87–10.90), P = 0.0008). Bone Marrow Transplantation (2001) 27, 575–580. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Scleromyxedema (SM) is a rare skin disorder related to monoclonal gammopathy. High dose intravenous immunoglobulins (HDIVIg) are usually used as a frontline therapy with initial efficacy. However, some patients evolve with relapse, refractory state or severe extra‐cutaneous complications such as dermato‐neuro syndrome (DNS) or cardiac involvement.The objective of the study is to evaluate the use of anti‐plasma cell treatment in these patients in order to obtain a deep and durable dermatological and haematological response.We report here eight patients treated with HDIVIg together with anti‐plasma cell therapy including: lenalidomide and dexamethasone (n = 5); bortezomib, cyclophosphamide and dexamethasone (n = 1); daratumumab, lenalidomide and dexamethasone (n = 2).Combination of HDIVIg with a treatment targeting the monoclonal component led to a high level of haematological remission and drastically improved skin response with an acceptable safety profile in all patients. Moreover, HDIVIg was reduced and stopped in 4 of the 7 patients who achieved complete remission.The association of lenalidomide and dexamethasone with HDIVIg could improve the treatment of relapsed or severe SM. [ABSTRACT FROM AUTHOR]

Seric hyperviscosity syndrome is a medical emergency linked to hyperproteinemia. The clinical diagnosis hinges on a triad of symptoms: mucosal hemorrhages, visual disturbances, and neurological disorders, observed in the most severe cases. Diagnosis is swiftly confirmed through an urgent fundoscopic examination. Therapeutic plasma exchange is the primary treatment for severe cases or following confirmation by fundoscopy. Laboratory tests predominantly identify the syndrome's etiology, with Waldenström's macroglobulinemia (characterized by a marked IgM peak) being the most common cause, followed by multiple myeloma and cryoglobulinemias. To prevent recurrence, targeted treatment of the underlying cause is implemented following plasma exchange sessions., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Melanoma, a deadly form of skin cancer, has witnessed a notable increase in incidence over the past decades. Despite advancements in treatment, it remains a significant cause of cancer mortality. Understanding demographic trends and variations in melanoma mortality is crucial for addressing disparities and implementing effective interventions., Methods: Using the Centers for Disease Control Wide Ranging Online Data for Epidemiologic Research (CDC WONDER) database, we analyzed melanoma mortality data in the United States from 1999 to 2020. Data were stratified by demographic and regional variables, and age-adjusted mortality rates were calculated. Descriptive analysis was performed and Joinpoint regression analysis was employed to identify temporal trends., Results: Between 1999 and 2020, there were 184,416 melanoma-related deaths in the United States Overall, the age-adjusted mortality rate declined from 2.7 to 2.0 per 100,000 people at a rate of -1.3% annually, with significant variations across demographic groups and regions. Men, non-Hispanic White individuals, and those aged > 65 experienced higher mortality rates. Non-Hispanic White individuals noted the steepest decrease in AAMR after 2013 at a rate of -6.1% annually. Disparities were seen by geographic density, with rural populations exhibiting higher mortality compared to their urban and suburban counterparts., Conclusion: The study highlights a significant reduction in melanoma mortality in the U.S. since 2013, potentially attributed to advancements in diagnostic techniques such as dermoscopy and the introduction of immune checkpoint inhibitors. Disparities persist, particularly among rural populations. Targeted interventions focusing on increased screening and education are warranted to further mitigate melanoma mortality and address demographic disparities., (© 2024. The Author(s).)

Current recommended risk scores to predict thrombotic events associated with myeloproliferative neoplasms (MPN) do not discriminate between arterial and venous thrombosis despite their different physiopathology. To define novel stratification systems, we delineated a comprehensive landscape of MPN associated thrombosis across a large long-term follow-up MPN cohort. Prior arterial thrombosis, age >60 years, cardiovascular risk factors and presence of TET2 or DNMT3A mutations were independently associated with arterial thrombosis in multivariable analysis. ARTS, an ARterial Thrombosis Score, based on these four factors, defined low- (0.37% patients-year) and high-risk (1.19% patients-year) patients. ARTS performance was superior to the two-tiered conventional risk stratification in our training cohort, across all MPN subtypes, as well as in two external validation cohorts. Prior venous thrombosis and presence of a JAK2 V617F mutation with a variant allelic frequency ≥50% were independently associated with venous thrombosis. The discrimination potential of VETS, a VEnous Thrombosis Score based on these two factors, was poor, similar to the two-tiered conventional risk stratification. Our study pinpoints arterial and venous thrombosis clinico-molecular differences and proposes an arterial risk score for more accurate patients' stratification. Further improvement of venous risk scores, accounting for additional factors and considering venous thrombosis as a heterogeneous entity is warranted., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Erythropoietic protoporphyria (EPP) is a rare metabolic disease of the heme biosynthetic pathway where an enzymatic dysfunction results in protoporphyrin IX (PPIX) accumulation in erythroid cells. The porphyrins are photo-reactive and are responsible for severe photosensitivity in patients, thus drastically decreasing their quality of life. The liver eliminates PPIX and as such, the main and rare complication of EPP is progressive cholestatic liver disease, which can lead to liver failure. The management of this complication is challenging, as it often requires a combination of approaches to promote PPIX elimination and suppress the patient's erythropoiesis. Here we described a 3-year follow-up of an EPP patient, with three episodes of liver involvement, aggravated by the coexistence of a factor VII deficiency. It covers all the different types of intervention available for the management of liver disease, right through to successful allogeneic hematopoietic stem cell transplantation., Competing Interests: The authors declare no competing financial interests., (© 2023 The Authors.)

The tropical rat mite (Ornithonyssus bacoti) commonly infests wild and pet rodents, but they are not host specific. Bodily contact with wild or domesticated rodents is the most common source of infestation. Mites can live off many mammal hosts for a long period of time; therefore, living in quarters infested by mice can lead to mite exposure. Human infestation presents as urticarial, pruritic, cutaneous lesions that may be misdiagnosed as an arthropod bite, an infection, or contact dermatitis. Symptomatic relief of pruritus can be provided with a topical corticosteroid or antihistamine. The most effective treatment is an antiparasitic, such as permethrin cream, as well as extermination of rodents, mites, and any other pests in the patient's living space.

Hyperviscosity syndrome (HVS) is a rare complication of newly diagnosed multiple myeloma (NDMM) related to high tumour burden. Studies about the prognosis of HVS in modern-era therapy for NDMM are missing. We investigated a retrospective cohort study of NDMM with HVS between 2011-2021. Thirty-nine NDMM patients with HVS were included. HVS presentation was heterogeneous, with asymptomatic, mild, and neurological forms in 23%, 59%, and 18% of cases, respectively. No thrombosis or major bleeding was observed. Therapeutic plasma exchanges were used in 92% of patients, which were effective and well tolerated. No rebound effect was observed. All patients except one had at least one CRAB criterion. Most of the patients received bortezomib and high-dose steroids (95%) associated with an immunomodulatory drug (43%) or alkylating agents (42%). HVS in NDMM patients had dismal overall survival matched to multiple myeloma patient controls (without HVS) in our center (median: 3.6 vs. 7.7 years, p=0.01), as confirmed by multivariate analysis. Early deaths (in the first two months) occurred in 21% of older patients (>65 years). HVS in NDMM patients is a rare but life-threatening complication associated with high lethality in older patients and be a potential dismal prognosis factor in the modern treatment era., Competing Interests: AB received support from OCTAPHARMA for attending a meeting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Debureaux, Harel, Parquet, Lemiale, Siguret, Goubeau, Morin, Royer, Cuccuini, Elessa, Theves, Brignier, Azoulay, Arnulf and Talbot.)

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed. We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0.018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0.93 and p = 0.28, respectively), and overall and grade 3-4 ICANS (p = 0.62 and p = 0.88, respectively). We observed no difference in the quality of CAR T-cells expansion (p = 0.79, %Cmax), nor in response rate (best ORR, 57.6% vs 61.8%, p = 0.93), nor survival even in a group of patients adjusted by a propensity score. In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T., (© 2021. The Author(s).)

Tisagenlecleucel therapy has shown promising efficacy for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, relapses occur in 30-50% of patients. Determinants for CD19 pos versus CD19 neg relapses are poorly characterized. We report on 51 patients with R/R BCP-ALL (median age 17 years) infused with tisagenlecleucel after lymphodepletion. Complete remission rate at D28 was 96%. Prior blinatumomab increased the risk of early failure at D28. The 18-month cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 51%, 44%, and 74%, respectively, at a median follow-up of 15.5 months. Factors associated with a high tumor burden (occurrence of cytokine release syndrome) and prior blinatumomab were associated with an increased CIR, and a shorter EFS and OS. Pre-lymphodepletion high disease burden (MRD ≥ 10 -2 , SHR 10.4, p = 0.03) and detectable MRD at D28 (SHR 7.2, p = 0.006) correlated with an increased risk of CD19 neg relapse. Low disease burden (SHR 5.3, p = 0.03) and loss of B-cell aplasia (BCA) (SHR 21.7, p = 0.004) predicted an increased risk of CD19 pos relapses. These data highlight the impact of prior therapy on patient outcome. Finally, detectable MRD at D28 and loss of BCA both define patients at high risk of relapse for whom additional interventions are needed., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Germ cell tumor (GCT) patients with brain metastases (BM) have a poor prognosis and high risk of treatment failure. Optimal therapies for these patients remain controversial. The aim of this study was to report the outcomes of all GCT patients with BM treated with high-dose chemotherapy (HDCT) in our French expert center for GCT., Methods: We carried out a retrospective study of 35 GCT patients with BM who were treated from 2003 to 2019 with HDCT, followed by infusions of autologous peripheral blood hematopoietic stem cells., Results: The overall survival at 2 years was 36.9% (95% confidence interval, 19.7-54). The median overall survival was 12 months and the median progression-free survival was 8 months. No variables were associated with better survival in the univariable analysis. Among the 35 patients included in our study, 31 completed HDCT and 4 stopped treatments after mobilization. Eleven patients (11) showed favorable responses (complete, partial, or stable disease) to HDCT and 20 patients died of disease progression (17) or toxicities (3). Among the 11 patients with favorable responses to HDCT, 8 (72.7%) had metachronous BM, mostly isolated. The majority of these patients did not receive local treatment at diagnosis or at relapse., Conclusions: Together, our study reveals that GCT patients can experience long-term survival even in the presence of BM. Metachronous BM can also be cured with HDCT even in the absence of local treatment. Biological and radiologic responses to mobilization could be a predictor of favorable responses to HDCT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)