Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.

Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy.

Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load was found to decrease slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load < 4.05 log10 copies/ml at immune effector cell-associated neurotoxicity syndrome (ICANS) onset identified patients at risk of progressing to severe forms of ICANS (OR 16.68, P = 0.048). Finally, patients who experienced falling or stable TTV DNA load between lymphodepletion and CAR-T infusion had better progression-free survival than those with ascending TTV DNA load (HR 0.31, P = 0.006). These findings suggest that TTV monitoring could serve as a surrogate marker of immune competence, enabling predictions of CAR-T efficacy and toxicity. This could pave the way for the development of TTV-guided therapeutic strategies that modulate clinical patient management based on plasma TTV load, similar to suggested strategies in solid organ transplant recipients.

Adenovirus-induced hemorrhagic cystitis after CD19-targeted chimeric antigen receptor T-cell therapy in a patient with large B-cell lymphoma.

Chimeric antigen receptor (CAR) T cells targeting CD19 have changed the treatment landscape of patients with relapsed/refractory diffuse large B-cell lymphoma. Infections are one of the most frequent complications after CAR T-cell therapy. Most of these infections are bacterial, although viral infections can also occur in this setting. Adenovirus-induced hemorrhagic cystitis is a rare infectious complication and is usually observed after bone marrow or solid organ transplantation. Herein we report a case of adenovirus-induced hemorrhagic cystitis in a patient experiencing urinary symptoms within the first month after CAR T-cell infusion. Based on our experience and a literature review, we discuss the diagnostic approach and potential treatment options for this infrequent infection after CAR T-cell therapy.

Lymphoma is an aggressive blood cell cancer. A treatment called chimeric antigen receptor (CAR) T-cell therapy has recently been developed for patients with lymphoma and other blood cancers. CAR T-cell therapy is based on the genetic change of the patient's T cells. T cells are a type of white blood cell, which help to attack cancer. CAR T-cell treatment is very effective, but it also carries a risk of adverse events, including infections. These infections can be caused by bacteria or viruses and can affect several organs, including the bladder. Patients with blood cancers who develop bladder infections can have severe pain and bleeding. These bleeding bladder infections are mostly caused by adenovirus or BK virus and are usually seen in patients who have received a bone marrow transplant. However, these infections are rarely observed in patients receiving CAR T cells. We report here a case of bleeding bladder infection caused by adenovirus in a patient receiving CAR T-cell therapy. We discuss the diagnostic approach and possible treatment options for this rare infection in CAR T-cell patients.

Impact of Cytomegalovirus Replication in Patients with Aggressive B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy.

Data are scarce on cytomegalovirus (CMV) replication in patients receiving CD19-directed chimeric antigen receptor (CAR) T cell treatment. Here we describe the incidence, severity, and management of CMV infection in patients with aggressive B cell lymphoma treated with CAR T cell therapy. In this retrospective observational study, we analyzed CMV viral load and its clinical impact in patients with aggressive B cell lymphoma receiving CAR T cell therapy between July 2018 and December 2021 at a single center. Patients with a negative baseline CMV IgG or a previous allogeneic stem cell transplantation were excluded. CMV replication was determined in whole blood. Overall, 105 patients met the study's inclusion criteria. Ten patients presented with CMV replication before CAR T cell infusion and were analyzed separately. Forty-two of the remaining 95 patients (44%) had at least 1 positive CMV determination, with a viral load ≥1000 IU/mL in 21 patients (22%). Four patients in the main cohort (N = 95) and 4 patients in the preinfusion replication group (N = 10) achieved a viral load >10,000 IU/mL. Only 7 patients received preemptive antiviral treatment. No CMV end-organ disease was reported. The sole independent risk factor associated with CMV viremia ≥1000 IU/mL was dexamethasone treatment (odds ratio, 8.4; 95% confidence interval, 2.4 to 36.6; P = .002). Based on our findings, we designed an algorithm for CMV management in this setting. CMV replication is relatively frequent in patients with aggressive B cell lymphoma receiving CAR T cell therapy. It is usually self-limited and not associated with end-organ disease. Patients receiving dexamethasone or harboring CMV replication before infusion might benefit from active surveillance and preemptive treatment strategies.

Algunas características clínicas de pacientes con retardo de crecimiento / Clinical aspects in patients with growth retardation

Se revisaron 2.118 fichas de la Unidad de Endocrinología y Genética Infantil del Hospital Paula Jaraquemada, durante dos años; y se estudiaron en forma retrospectiva los retardos de crecimiento (RC), que corresponden a 34% (700 casos). La mitad de ellos consultó por esta causa, siendo su etiología más frecuente la constitucional o familiar (42,7%). Las edades de consulta más frecuentes fueron las escolares y la adolescencia. Los RC por enfermedad genética tienen más frecuentemente bajo peso al nacer y antecedentes de PEG. En los RC por enfermedad endocrina, genética o por otras causas, se observa mayor proporción de pacientes con retraso psicomotor y escolaridad inadecuada que en los RC constitucionales o familiares. La talla y velocidad de crecimiento está más comprometida en los RC debidos a enfermedad genética y endocrina que en los constitucionales o familiares; y la edad ósea está más retrasada en los RC endocrinos que en el resto de los RC. El adecuado estudio clínico y la identificación del canal de crecimiento de estos pacientes, son elementos fundamentales para hacer oportunamente el diagnóstico

Nuevos conceptos en hiperplasia suprarrenal virilizante (HSRV) por bloqueo de la 21-hidroxilasa / New concepts in virilizing adrenal hyperplasia due to 21-hydroscylase blocking

El estudio del haplotipo HLA en una familia, cuando hay un caso conocido de HSRV (perdedora o no perdedora de sal) es útil en la práctica para identificar heterozigotos, portadores sanos de la enfermedad y permite dar consejo genético a las parejas. El haplotipo HLA es útil en el diagnóstico intrauterino de la enfermedad, a partir del estudio del líquido amniótico en embarazadas parientes de un apaciente con HSRV. El haplotipo HLA también puede ser útil para identificar otros pacientes en una familia con un caso de la forma no clásica o post-puberal de la enfermedad y ayuda a hacer un diagnóstico precoz, especialmente en el sexo masculino, en que los signos físicos de esta forma clínica son muy difíciles de detectar. El haplotipo HLA hasta el presente no sirve para identificar enfermos ni portadores en la población general, ya que no funciona como un marcador genético y no hay asociación entre un haplotipo HLA determinado y la enfermedad en la población general. La 17-OHP es útil en el diagnóstico de todas las formas clínicas de HSRV. En el RN la 17-OHP está elevada precozmente y es de gran ayuda, ya que en estos casos los 17KS y el PNT urinario generalmente no se elevan significativamente. La determinación de 17-OHP por RIA en muestras de sangre tomadas en papel filtro pueden ser usadas para el rastreo de la enfermedad en los RN de una población con alta incidência de la afección. El estudio de 17-OHP, después del estímulo con ACTH, puede permitir detectar pacientes con formas no clásicas de la enfermedad e identificar alrededor del 75% de los portadores sanos (heterozigotos). La interpretación cuidadosa de las concentraciones plasmáticas de 17-OHP en dos horarios del día (8 AM y 5 PM) es útil en el control del tratamiento de los pacientes pediátricos. La testosterona plasmática (en mujeres de cualquier edad y en niños entre 1 y 9 años) y la - 4 - androstenediona plasmática (en ambos sexos sin importar edad) son útiles para controlar el tratamiento de estos pacientes si se consideran en conjunto con los criterios clásicos y con otros más recientes que se comentan en esta publicación. La actividad aumentada de renina plasmática en sujetos con HSRV es un criterio biológico moderno para identificar pacientes perdedores de sal, aunque clínicamente nunca hayan presentado crisis de pérdida de sal y para decidir si es necesario agregar mineralocorticoides al tratamiento