Enfermedad injerto contra huésped en el trasplante de sangre de cordón umbilical de donante no emparentado en adultos con enfermedades hematológicas malignas

Comparado con la sangre periférica y la médula ósea como fuentes de progenitores hematopoyéticos de donante no emparentado, la sangre de cordón umbilical desencadena una menor alorreactividad contra el receptor, lo que permite el uso de donantes con una mayor disparidad del sistema HLA. Un menor número de linfocitos T en la unidades de cordón umbilical (UCU), pero con un mayor porcentaje de linfocitos T naive, explica en parte la menor incidencia de enfermedad injerto contra huésped (EICH) en el trasplante de sangre de cordón umbilical (TSCU) en comparación con otras fuentes. Sin embargo, este porcentaje relativamente bajo no impide que esta complicación contribuya directa e indirectamente a la morbilidad y mortalidad en una proporción significativa de pacientes. Conocer en detalle la incidencia, formas y grados de presentación y los factores predictivos de desarrollo de la EICH, así como la respuesta a los tratamientos, podrían ayudarnos a implementar nuevas estrategias de prevención y tratamiento más eficaces. Este trabajo analiza la EICH aguda y crónica en 300 pacientes adultos consecutivos con hemopatías malignas sometidos a TSCU con acondicionamiento mieloablativo. Se trata de un estudio retrospectivo que recoge la experiencia del Hospital La Fe de Valencia a lo largo de casi 19 años. Con una mediana de seguimiento superior a los 5 años, este estudio muestra datos de supervivencia global (SG) comparable a otras series no seleccionadas con diferentes fuentes de progenitores hematopoyéticos. El autotrasplante impactó de forma significativa en la SG. La incidencia de EICH aguda global fue del 62% y II-IV del 39%, e influye en gran medida en la morbimortalidad del procedimiento, sobre todo infecciosa (73% de las causas de muerte). La incompatibilidad de sexo entre donante (mujer) y receptor (varón) se distinguió como factor de riesgo para el desarrollo de formas graves de EICH aguda. El porcentaje de respuestas al tratamiento de primera línea (corticoides 2 mg/kg o 20 mg/kg) de la EICH aguda fue del 69%, sin detectarse diferencias entre la dosis de corticoides en cuanto al porcentaje de respuestas o SG. La LDH parece útil a la hora de predecir la respuesta y el pronóstico tras el tratamiento de la EICH. Aquellos pacientes con EICH aguda y corticoides sistémicos tuvieron una peor recuperación de linfocitos B y T helper 3 y 6 meses después del trasplante, lo que puede ayudar a explicar el mayor porcentaje de muertes por causa infecciosa en estos pacientes. La incidencia global de EICH crónica fue del 60%, con un 41% de formas extensas. El hecho de haber desarrollado la EICH aguda con anterioridad parece influir en la probabilidad de desarrollar la EICH crónica, sobre todo en su forma extensa. Como conclusión, este trabajo podrá mejorar la selección de los pacientes y de las UCU, optimizar los esquemas de profilaxis de la EICH, e impulsar la investigación sobre factores de riesgo, clasificación y factores predictivos de respuesta al tratamiento de la EICH

Monitoring of plasma Torque teno virus, total Anelloviridae and Human Pegivirus 1 viral load for the prediction of infectious events and acute graft versus host disease in the allogeneic hematopoietic stem cell transplantation setting

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log10 (pretransplant) and ≥4.58 log10 (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log10 by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from HLA-matched sibling donor, 101 (42%) from HLA-matched and mismatched unrelated donor, and 64 (26%) from haploidentical donor. Except for neutrophil and platelet engraftment, which was slower in the haploidentical cohort, no significant differences were observed in major transplant outcomes according to donor type in univariate and multivariate analysis. GvHD prophylaxis with Sir-PTCy, with or without MMF, is safe and effective in patients with AML undergoing myeloablative allo-HSCT, resulting in low rates of transplant-related mortality, relapse/progression, and acute and chronic GvHD in all donor settings

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P =0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P =0.003, and 42% vs. 16%, P <0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P =0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P =0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P =0.195), 51% and 47% (P =0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products