Neuropatía múltiple como manifestación clínica de una recidiva de leucemia / Isolated multiple neuropathy as clinical manifestation of leukemia relapse

Introducció La neuroleucemiosis es una rara enfermedad del sistema nervioso periférico producida por la infiltración por células leucémicas. Caso clínico: Presentamos el caso de una paciente de 34 años con antecedente de una leucemia mielomonoblástica aguda en remisión, que presentaba una parálisis progresiva del nervio mediano derecho, del facial bilateral y del peroneal izquierdo. El electromiograma confirmó el diagnóstico de una neuropatía múltiple. La tomografía por emisión de positrones-tomografía computarizada mostró un hipermetabolismo de ambos nervios ciáticos, facial bilateral y mediano derecho. La biopsia de médula ósea confirmó la recidiva de la leucemia, por lo que se inició un nuevo ciclo de quimioterapia con mejoría de los déficits neurológicos. Conclusión: La infiltración del sistema nervioso periférico por células leucémicas puede simular múltiples síndromes neurológicos dependiendo de las estructuras afectadas. La barrera hematonerviosa actúa como defensa de las células leucémicas contra la quimioterapia y el sistema inmunitario, por lo que el sistema nervioso periférico constituye un reservorio de las células leucémicas. Por ello, la neuroleucemia debe considerarse en pacientes con antecedentes de leucemia que presenten síntomas aislados de afectación del sistema nervioso periférico.(AU)

Introduction: Neuroleukemia is a rare disorder of the peripheral nervous system due to leukemic cell infiltration. Case report: We present the case of a 34-year-old patient with history of acute myelomonoblastic leukemia in remission that presented progressive paresis of the right median, bilateral facial, and left peroneal nerves. The electromyogram confirmed the diagnosis of multineuropathy. A PET-CT showed hypermetabolism of both sciatic, facial, and right median nerves. A bone marrow aspirate confirmed the leukemia relapse so a new round of chemotherapy was performed with improvement of the neurological deficit. Conclusion: Peripheral nervous system infiltration by leukemic cells can mimic multiple syndromes depending on the structures involved. The nerve-blood barrier acts as a defense of leukemic cells against chemotherapy and the immune system. Thus, the peripheral nervous system constitutes a reservoir of leukemic cells. Neuroleukemia should be considered in patients with history of acute leukemia who have isolated symptoms of the peripheral nerve.(AU)

Isolated multiple neuropathy as clinical manifestation of leukemia relapse. / Neuropatía múltiple como manifestación clínica de una recidiva de leucemia.

INTRODUCTION: Neuroleukemia is a rare disorder of the peripheral nervous system due to leukemic cell infiltration. CASE REPORT: We present the case of a 34-year-old patient with history of acute myelomonoblastic leukemia in remission that presented progressive paresis of the right median, bilateral facial, and left peroneal nerves. The electromyogram confirmed the diagnosis of multineuropathy. A PET-CT showed hypermetabolism of both sciatic, facial, and right median nerves. A bone marrow aspirate confirmed the leukemia relapse so a new round of chemotherapy was performed with improvement of the neurological deficit. CONCLUSION: Peripheral nervous system infiltration by leukemic cells can mimic multiple syndromes depending on the structures involved. The nerve-blood barrier acts as a defense of leukemic cells against chemotherapy and the immune system. Thus, the peripheral nervous system constitutes a reservoir of leukemic cells. Neuroleukemia should be considered in patients with history of acute leukemia who have isolated symptoms of the peripheral nerve.

TITLE: Neuropatía múltiple como manifestación clínica de una recidiva de leucemia.Introducción. La neuroleucemiosis es una rara enfermedad del sistema nervioso periférico producida por la infiltración por células leucémicas. Caso clínico. Presentamos el caso de una paciente de 34 años con antecedente de una leucemia mielomonoblástica aguda en remisión, que presentaba una parálisis progresiva del nervio mediano derecho, del facial bilateral y del peroneal izquierdo. El electromiograma confirmó el diagnóstico de una neuropatía múltiple. La tomografía por emisión de positrones-tomografía computarizada mostró un hipermetabolismo de ambos nervios ciáticos, facial bilateral y mediano derecho. La biopsia de médula ósea confirmó la recidiva de la leucemia, por lo que se inició un nuevo ciclo de quimioterapia con mejoría de los déficits neurológicos. Conclusión. La infiltración del sistema nervioso periférico por células leucémicas puede simular múltiples síndromes neurológicos dependiendo de las estructuras afectadas. La barrera hematonerviosa actúa como defensa de las células leucémicas contra la quimioterapia y el sistema inmunitario, por lo que el sistema nervioso periférico constituye un reservorio de las células leucémicas. Por ello, la neuroleucemia debe considerarse en pacientes con antecedentes de leucemia que presenten síntomas aislados de afectación del sistema nervioso periférico.

Usefulness of high-frequency ultrasonography in the evaluation and monitoring of sclerosing dermatoses: a cohort study.

BACKGROUND: Monitoring of disease activity in sclerosing dermatoses (SD) can be challenging and tools to support clinical decision-making are lacking. AIM: To analyse the impact of high-frequency ultrasonography (HFUS) on the clinical management of SD and to describe the US characteristics of disease activity. METHODS: This was a cohort study of patients with various SD [morphoea, systemic sclerosis (SS) and chronic graft-versus-host disease (cGvHD)] who underwent HFUS between January 2017 and August 2019. HFUS criteria for diagnosing active SD were increased Doppler vascularity and/or meeting all B-mode greyscale US signs of activity. Discordance in SD activity between HFUS and clinical examination was evaluated at the time of the first US assessment. Changes in patient management were instituted after HFUS were recorded. RESULTS: In total, 72 patients (31 with morphoea, 19 with SS and 22 with cGvHD), who underwent 163 HFUS sessions in total, were included. All HFUS-active morphoea lesions exhibited increased vascularity, and all HFUS-active SS exhibited dermal thickening and dermal hypoechogenicity. HFUS-active cGvHD displayed increased dermal thickness and loss of definition of the dermal-hypodermal junction, and there were signs of panniculitis in 80% of cases and of increased vascularity in 70%. Discordance in disease activity between clinical and HFUS evaluation was found in 17 (23.6%) patients. Changes in clinical management after HFUS were made for 14 (19.4%) patients: treatment discontinuation for 6 patients (42.9%), treatment initiation for 5 (35.7%), medication change for 2 (14.3%) and skin biopsy taken for 1 (7.1%). CONCLUSION: HFUS seems an efficacious support tool in the monitoring of SD activity with a notable impact on clinical management. Further studies are warranted to evaluate the impact of HFUS-supported management changes on SD outcomes.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies.

OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result. RESULTS: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.

Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution.

The role of allogeneic hematopoietic SCT (allo-HCT) in multiple myeloma (MM) remains controversial. A total of 58 patients received an allo-HCT (25 of them with myeloablative conditioning-allo-MAC-and 33 with reduced-intensity conditioning-allo-RIC) at our institution over a 28-year period. The CR rate for allo-MAC was 36%. The incidence of grade III-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) was 28% and 39%, respectively The TRM at any time was 60% and the main causes of death were aGVHD or infectious complications not directly related to GVHD. The estimated PFS and OS at 15 years were 8% and 15%, respectively. The CR rate with allo-RIC was 45%. The incidence of grade III-IV aGVHD and cGVHD were 24% and 41%, respectively. The TRM at any time was 33% and was mainly related to aGVHD. The estimated PFS and OS at 5 years were 22% and 38%, respectively. Despite its high TRM, a proportion of patients with high-risk myeloma (early relapse and newly diagnosed ultrahigh risk) may obtain long-term disease control with allo-HCT. New approaches aimed at decreasing the incidence of aGVHD, and consequently to decrease the TRM, are needed.

A variant in IRF3 impacts on the clinical outcome of AML patients submitted to Allo-SCT.

Allo-SCT has a strong curative potential for AML patients mainly due to a GVL effect. Unfortunately, GvL and GVHD are intimately linked. IFN regulatory factor-3 (IRF3), by modulating innate immune reactions, could impact on the incidence and intensity of GVL and GVHD. We analyzed two gene variants in IRF3 (rs7251 and rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical sibling allo-SCT. Patients with a donor carrying the dominant GG gene variant in rs7251 had, as compared with GC and CC variants, a lower acute GVHD (aGVHD) III-IV incidence (4% vs 11% vs 27%; P=0.0078), a higher relapse incidence (49% vs 35% vs 26%; P=0.018), and lower TRM (7% vs 24% vs 18%; P=0.0065). In functional studies, the GG variant was associated with lower production of IFN-γ, decreased lymphocyte proliferation after antigen presentation by DCs, and lower cytotoxic response of mature natural killer cells. Patients carrying the AA dominant variant in rs2304205 had higher relapse incidence (50% vs 39% vs 18%, P=0.0068). The presence of both variants (GG in rs7251 and AA in rs2304205) in donors and patients resulted in a stronger clinical impact.

A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT.

An adequate response of the innate immune system after allo-SCT is crucial for the clinical outcome of patients submitted to this procedure. EP300 is one of the key genes of the innate immune system (IIS). We evaluated the influence of gene variant A>G rs20551 in EP300 in donor and/or recipient on clinical results after HLA-identical sibling allo-SCT. Patients with AA gene variant had a lower relapse incidence (31 vs 48%, P=0.025; odds ratio (OR)=1.6, P=0.05), attained better disease-free survival (AA: 53% vs AG+GG: 24%, P=0.001; OR=1.8, P=0.01), and better OS (AA: 53% vs AG+GG: 34%, P=0.001; OR=1.9, P=0.007). This beneficial association was more evident when AA gene variant was present in both donor and patient. In healthy individuals, AA gene variant was associated with lower IL2 production after a mitogenic stimuli, higher CD4+ cell response after CMV infection, and higher expression of innate immune genes (IRF-3 and MIF), cell cycle genes (AURKB, CCNA2 and CCNB1), lymphocyte survival genes (NFAT5 and SLC38A2), and with a lower expression of P53 compared with recessive GG gene variant. These findings suggest a beneficial effect of the AA gene variant in rs20551 on clinical outcome after allo-SCT.