Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.

BACKGROUND: A variable incidence of profound cytopenia has been described in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). This complication leads to severe infection in some cases, especially those who present additional risk factors including prior hematopoietic stem cell transplantation (HSCT). STUDY DESIGN AND METHODS: We report a case of breakthrough invasive fungal infection in a patient with prolonged neutropenia after CAR-T cell therapy administered for relapsed B-cell ALL after allogeneic haploidentical HSCT. RESULTS: After disease progression was discarded, therapy with antifungal agents, G-CSF and thrombopoietin analogue was started. However, no sign of haematological recovery or infection improvement was observed. A fresh mobilized selected CD34-stem cell boost from her haploidentical transplant donor was infused without further conditioning. Within 15 days of mobilized CD34-boost administration the patient showed complete resolution of both the aplasia and fungal infection. DISCUSSION: This case illustrates as proof-of-concept the efficacy and safety of selected CD34-stem cell boost from prior donor as salvage treatment of prolonged cytopenias after CAR-T cell therapy.

Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel.

Chimeric antigen receptor (CAR) T cell-related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with poor prognosis and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR T-cell follow-up, allows a more precise management of this complication.

A mild deficiency of ADAMTS13 is associated with severity in COVID-19: comparison of the coagulation profile in critically and noncritically ill patients.

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.

Successful Treatment of Severe Aspergillosis with Isavuconazole Therapy after Allogeneic Stem Cell Transplantation.

Invasive fungal infections are one of the main infectious complications in allogeneic stem cell transplantation (SCT). Triazoles (voriconazole, posaconazole) are the main prophylactic and therapeutic options for the treatment of invasive aspergillosis. However, pharmacological interactions and hepatotoxicity limit its use. Isavuconazole (ISV) is a recently approved azole with a promising interaction and safety profile. We present a case with invasive aspergillosis in the post-allogeneic SCT setting in a critically ill patient with severe multiorgan failure due to veno-occlusive disease. The patient was treated with ISV and B amphotericin during severe kidney and liver failure and multiple immunosuppressants, without significant drug-related toxicity and with favorable outcome. The interaction and safety profile of ISV is discussed along the reported experience. ISV can be an effective salvage therapy even in complex clinical situations with multiple potential interactions.

[Aortic root homograft in the surgical treatment of aortic valve disease with dilated ascending aorta]. / Homoinjerto de raíz aórtica para el tratamiento quirúrgico de las afecciones de la válvula aórtica con aorta ascendente dilatada.

INTRODUCTION AND OBJECTIVES: Patients with aortic valve disease and a dilated ascending aorta are usually treated with a composite graft comprising a valve and conduit. We review here the results of treatment with an aortic root homograft as a valid alternative. PATIENTS AND METHOD: Twenty-two consecutive patients with a mean age of 64.8 (8.8) years were studied. Mean ascending aorta dilation was 54.55 mm, aortic valve insufficiency was present in 16 patients, and a combined lesion was present in 6. In all cases a cryopreserved aortic root homograft was used to replace the aortic valve and ascending aorta. In 9 cases a Dacron conduit was used beyond the sinotubular junction to restore continuity between the homograft and the native aorta. RESULTS: All patients survived surgery. One patient had postoperative systemic inflammatory response syndrome and one patient was re-explored for excessive bleeding. Mean duration of follow-up was 12.1 months (range 2-36 months). No patient was given anticoagulants, and one had an early transient cerebrovascular accident followed by complete recovery. At one month postsurgery the left ventricular systolic (P<.001) and diastolic (P<.009) diameters had decreased significantly on echocardiography, and these decreases persisted throughout follow-up. The caliber of the ascending aorta was normal in all patients (< or =30 mm) except one. CONCLUSIONS: Aortic root homografts are a valid alternative in the treatment of aortic valve disease with ascending aorta dilation. The main advantages of this therapy are that permanent anticoagulation is not needed, and that left ventricular dimensions recover rapidly.

Homoinjerto de raíz aórtica para el tratamiento quirúrgico de las afecciones de la válvula aórtica con aorta ascendente dilatada / Aortic root homograft in the surgical treatment of aortic valve disease with dilated ascending aorta

Introducción y objetivos. Los pacientes con afección de la válvula aórtica y dilatación de la aorta ascendente son tratados habitualmente con tubos valvulados. Revisamos los resultados del uso de homoinjertos de raíz aórtica como alternativa terapéutica válida. Pacientes y método. Se incluyó en el estudio a un total de 22 pacientes consecutivos con una edad media, 64,8 ñ 8,8 años. La dilatación media de la aorta ascendente fue de 54,45 mm y la válvula aórtica presentaba insuficiencia pura en 16 pacientes; en 6 pacientes había doble lesión. En todos los casos se usaron homoinjertos criopreservados para sustituir la raíz aórtica y la aorta ascendente. En 9 casos se prolongó la unión sinotubular con una prótesis para restablecer la continuidad entre el homoinjerto y la aorta nativa. Resultados. No hubo muertes hospitalarias ni en el seguimiento. Un paciente padeció un síndrome de respuesta inflamatoria sistémica y otro fue reintervenido por hemorragia. El seguimiento medio fue de 12,1 meses (rango, 2-36 meses). No se administró anticoagulación a ningún paciente. Un paciente tuvo un accidente cerebrovascular transitorio sin secuelas. Se observó mediante ecocardiografía una reducción estadísticamente significativa de los diámetros ventriculares al mes de la cirugía (diámetro sistólico del ventrículo izquierdo p < 0,001; diastólico, p < 0,009) que se mantuvo durante el seguimiento. Todos los enfermos presentan calibre normal de la aorta ascendente ( 30 mm), excepto uno. Conclusiones. Los homoinjertos de raíz aórtica constituyen una alternativa válida para el tratamiento de las afecciones de la válvula aórtica asociadas a dilatación de la aorta ascendente. La no necesidad de anticoagulación y la rápida recuperación de los diámetros ventriculares izquierdos son los pilares fundamentales de este tratamiento (AU)