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1.
Eur J Haematol ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143681

RESUMEN

This study evaluates the feasibility of using post-transplant cyclophosphamide (PTCY) prophylaxis in allo-hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft-versus-host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty-seven adults aged 65 or older with hematological malignancies, undergoing their first allo-HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II-IV and III-IV acute GVHD, and the 2-year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2-year overall survival, non-relapse mortality, cumulative incidence of relapse, and GVHD-free relapse-free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65-69. This study confirms the safety and feasibility of PTCY-based allo-HCT in older adults.

2.
Am J Hematol ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215605

RESUMEN

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39117736

RESUMEN

Since 2021 the use of G-CSF was implemented in allo-HCT with PTCY-based prophylaxis with the aim of shortening the aplastic phase and reducing infectious complications. This study investigates the effectiveness of this change in protocol performed at our institution. One-hundred forty-six adults undergoing allo-HCT with PTCY-based prophylaxis were included, and among them, 58 (40%) received G-CSF. The median of days to neutrophil engraftment was shorter in the G-CSF group (15 vs. 20 days, p < 0.001). Patients receiving G-CSF had a lower incidence of day +30 bacterial bloodstream infections (BSI) than the rest (20.7% vs. 47.7%, p < 0.001). GVHD, SOS, and TA-TMA incidences were comparable between groups, and using G-CSF did not impact on survival. Endothelial activation was investigated using EASIX and by the measurement of soluble biomarkers in cryopreserved plasma samples obtained on days 0, +7, +14 and +21 of 39 consecutive patients (10 received G-CSF) included in the study. EASIX, VWF:Ag, sVCAM-1, sTNFRI, ST2, REG3α, TM and NETs medians values were comparable in patients receiving G-CSF and those who did not. Compared with allo-HCT performed without G-CSF, the addition of G-CSF to PTCY-based allo-HCT accelerated neutrophil engraftment contributing on decreasing BSI incidence, and without inducing additional endothelial activation.

4.
Cancers (Basel) ; 16(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39061206

RESUMEN

PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II-IV and III-IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14-16) and 16 days (IQR 12-23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile.

5.
Bone Marrow Transplant ; 59(9): 1209-1214, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38961259

RESUMEN

Extracorporeal photopheresis (ECP) is a therapy that combines the collection of mononuclear cells by apheresis, the addition of a photosensitizer (8-methoxisoralen), the illumination of the product with ultraviolet A light, and the immediate infusion of the product to the patient. Initially developed and approved to treat T-cell cutaneous lymphomas, soon started to be used to treat graft versus host disease (GvHD) developed after allogeneic hematopoietic-cell transplantation. The high response rate of ECP in skin, ocular, oral, pulmonary, and liver forms of chronic GvHD, the steroid-sparing effect, and the improved overall survival of treated patients, made ECP one of the second-line treatments used to treat steroid-resistant acute and chronic GVHD. Recently, the development of new drugs for treating GVHD has changed the position of ECP in the therapy of GVHD and has started to be used in combination with drugs for increasing the response rate to the treatment in severe or resistant forms of acute and chronic GVHD. ECP remains an essential therapeutic resource in the management of patients with refractory acute and chronic GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Fotoféresis , Fotoféresis/métodos , Humanos , Enfermedad Injerto contra Huésped/terapia , Enfermedad Crónica , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Aguda
6.
Leukemia ; 38(9): 2016-2022, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39048722

RESUMEN

An increasing number of older patients with acute myeloid leukemia (AML) are offered an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Normally, older patients have older matched related donors (MRD). Matched unrelated donors (MUD) are an important alternative, but it remains unclear whether a younger MUD is associated with better outcomes, especially in the context of post-transplant cyclophosphamide (PTCy). We compared outcomes of patients older than 50 years with AML in first complete remission (CR1) and receiving a first HSCT from a 10/10 MUD aged younger than 40 years to those receiving a graft from a MRD aged older than 50 years, using PTCy and with well-known transplant conditioning intensity (TCI) score. A total of 345 consecutive patients were included and classified according to TCI score as low, intermediate, or high. On multivariable analysis in the TCI-intermediate/high group, MUD was associated with better graft-versus-host disease-free, relapse-free survival, lower non-relapse mortality and lower relapse incidence. For patients receiving a TCI-low regimen, outcomes are independent on the type of donor. In patients with AML in CR1, older than 50 years and receiving a TCI-intermediate/high conditioning regimen using PTCy, a MUD younger than 40 years is preferable over a MRD older than 50 years.


Asunto(s)
Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Inducción de Remisión , Acondicionamiento Pretrasplante , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Masculino , Adulto , Anciano , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado , Factores de Edad , Trasplante Homólogo , Enfermedad Injerto contra Huésped/etiología , Adulto Joven , Pronóstico
7.
Blood Adv ; 8(18): 4792-4802, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39008719

RESUMEN

ABSTRACT: It has been reported in prospective randomized trials that antithymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis has benefits in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with unrelated donors (UDs). However, the optimal GVHD prophylaxis strategy has been challenged recently by the increasing use of posttransplant cyclophosphamide (PTCY). We report from the European Society for Blood and Marrow Transplantation registry the outcomes of 960 patients with myelodysplastic neoplasms who underwent allo-HSCT from UD with PTCY or ATG as GVHD prophylaxis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The disease characteristics were similar in both groups. Day 28 neutrophil engraftment was significantly better with ATG (93% vs 85%). Over a median follow-up of 4.4 years, the 5-year OS was 58% with PTCY, and 49% in the ATG group. The 5-year PFS was higher for PTCY at 53% vs 44% for ATG. Grade 2 to 4 acute GVHD incidence was lower when PTCY was used (23%), whereas there was no difference in the incidence of chronic GVHD at 5 years. Multivariable analyses confirmed better OS and PFS with PTCY with a hazard ratio (HR) for ATG of 1.32 (1-1.74) and a better PFS for PTCY with a HR for ATG of 1.33. This study suggests that GVHD prophylaxis using PTCY instead of ATG in this setting remains a valid option. Further prospective randomized studies would be essential to confirm these results.


Asunto(s)
Suero Antilinfocítico , Ciclofosfamida , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Donante no Emparentado , Humanos , Ciclofosfamida/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Persona de Mediana Edad , Femenino , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Adulto , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/mortalidad , Anciano , Adulto Joven , Trasplante Homólogo , Acondicionamiento Pretrasplante/métodos , Adolescente , Resultado del Tratamiento
8.
Transplant Cell Ther ; 30(9): 914.e1-914.e8, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38851323

RESUMEN

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). However, its characterization after haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) is scarce. This study aimed to describe characteristics and outcomes of patients with SOS/VOD after haplo-HSCT with PT-Cy. We conducted a retrospective study of 797 patients undergoing a haplo-HSCT with PT-Cy between 2007 and 2019 in 9 centers in Spain. SOS/VOD was defined according to modified Seattle, Baltimore, or revised European Society for Blood and Marrow Transplantation (EBMT) criteria. Severity was graded retrospectively according to revised EBMT severity criteria into 4 categories: mild, moderate, severe, and very severe. From a total of 797 haplo-HSCTs performed, 46 patients (5.77%) were diagnosed with SOS/VOD at a median of 19 days (range, 4 to 84 days) after transplantation. Based on revised EBMT severity criteria, the SOS/VOD cases were classified as mild (n = 4; 8.7%), moderate (n = 10; 21.7%), severe (n = 12; 26.1%), and very severe (n = 20; 43.5%). Overall, 30 patients (65%) achieved SOS/VOD complete response, 25 (83%) of whom were treated with defibrotide. Twenty patients (43%) died before day +100 post-HSCT. Death was attributed to SOS/VOD in 11 patients, and 5 patients died of other causes without resolution of SOS/VOD. The incidence of SOS/VOD after haplo-HSCT with PT-Cy was comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria. Despite a promising SOS/VOD complete response (CR) rate (65%), 100-day mortality remained high (43%), indicating that further improvement in the management of this potentially fatal complication is needed.


Asunto(s)
Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Trasplante Haploidéntico , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/etiología , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Masculino , Femenino , Ciclofosfamida/uso terapéutico , Adulto , Adolescente , Estudios Retrospectivos , Persona de Mediana Edad , España/epidemiología , Adulto Joven , Niño , Anciano , Preescolar , Acondicionamiento Pretrasplante/efectos adversos
9.
J Crohns Colitis ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757210

RESUMEN

BACKGROUND AND AIM: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn's disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT's safety and efficacy using a cyclophosphamide (Cy)-free mobilisation regimen. METHODS: A prospective observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12-16 µg/kg/daily for 5 days, and optional Plerixafor 240 µg/d (1-2 doses) if the CD34+ cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up. RESULTS: All patients achieved successful outpatient mobilisation (7 patients needed Plerixafor) and underwent transplantation. Median follow-up was 106 weeks (IQR 52-348). No mobilisation-related serious adverse events (SAEs) or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation. CONCLUSIONS: Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction.

10.
Br J Haematol ; 205(1): 256-267, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38811025

RESUMEN

European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia-free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse-plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2-year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo-HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Pronóstico , Anciano , Estudios Retrospectivos , Trasplante Homólogo , Adolescente , Adulto Joven , Mutación , Medición de Riesgo/métodos , Supervivencia sin Enfermedad , Proteína del Locus del Complejo MDS1 y EV11/genética
11.
Bone Marrow Transplant ; 59(8): 1137-1145, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38755458

RESUMEN

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22-38] versus 47% [95% CI, 36-59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5-20]) compared to TBI (25% [95% CI, 18-33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40-58] and 46% [95% CI, 35-60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.


Asunto(s)
Busulfano , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tiotepa , Acondicionamiento Pretrasplante , Irradiación Corporal Total , Humanos , Irradiación Corporal Total/métodos , Acondicionamiento Pretrasplante/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Busulfano/uso terapéutico , Busulfano/administración & dosificación , Adulto , Tiotepa/administración & dosificación , Tiotepa/uso terapéutico , Femenino , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Adolescente , Adulto Joven , Trasplante Homólogo/métodos
13.
Pharmaceuticals (Basel) ; 17(5)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38794124

RESUMEN

Tacrolimus (Tac) is pivotal in preventing acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). It has been reported that genetic factors, including CYP3A5*3 and CYP3A4*22 polymorphisms, have an impact on Tac metabolism, dose requirement, and response to Tac. There is limited information regarding this topic in alloHSCT. The CYP3A5 genotype and a low Tac trough concentration/dose ratio (Tac C0/D ratio) can be used to identify fast metabolizers and predict the required Tac dose to achieve target concentrations earlier. We examined 62 Caucasian alloHSCT recipients with a fast metabolizer phenotype (C0/dose ratio ≤ 1.5 ng/mL/mg), assessing CYP3A5 genotypes and acute GVHD incidence. Forty-nine patients (79%) were poor metabolizers (2 copies of the variant *3 allele) and 13 (21%) were CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3 genotypes). CYP3A5 expressers had lower C0 at 48 h (3.7 vs. 6.2 ng/mL, p = 0.03) and at 7 days (8.6 vs. 11.4 ng/mL, p = 0.04) after Tac initiation, tended to take longer to reach Tac therapeutic range (11.8 vs. 8.9 days, p = 0.16), and had higher incidence of both global (92.3% vs. 38.8%, p < 0.001) and grade II-IV acute GVHD (61.5% vs. 24.5%, p = 0.008). These results support the adoption of preemptive pharmacogenetic testing to better predict individual Tac initial dose, helping to achieve the therapeutic range and reducing the risk of acute GVHD earlier.

14.
Transfus Med Rev ; 38(2): 150824, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38569349

RESUMEN

Limited data regarding elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in mobilized donors with G-CSF is available. We extended these findings by examining serum NT-proBNP in a cohort study including 35 healthy donors and 69 patients who received G-CSF for CD34+ mobilization as well as 54 patients who did not receive G-CSF but who underwent collection of CD3+ cells for chimeric antigen receptor (CAR) T-cell manufacturing. No donor in the three cohorts experienced significant cardiac adverse events. NT-proBNP levels were measured before and after G-CSF administration and after finishing apheresis procedure. NT-proBNP increase was observed in mobilized healthy donors after G-CSF administration, but was not observed in mobilized or non-mobilized patients. Only in the cohort of healthy donors, pairwise comparisons using Wilcoxon signed ranks test showed a significant increase between the mean serum NT-proBNP level after G-CSF administration and the mean serum NT-proBNP level measured before G-CSF administration (231.09 ± 156.15 pg/mL vs. 58.88 ± 26.84 pg/mL; P < .01). No correlation was observed between NT-proBNP increase and G-CSF dose (rs = 0.09; n = 32; P = .6) and no other variables contributing to predict serum NT-proBNP increase were detected. In conclusion, we observed a statistically, although not clinically, significant increase of NT-proBNP in healthy donors who received G-CSF as CD34+ cell mobilization.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Masculino , Factor Estimulante de Colonias de Granulocitos/sangre , Femenino , Movilización de Célula Madre Hematopoyética/métodos , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Anciano , Donantes de Sangre , Antígenos CD34
15.
Blood ; 143(24): 2534-2543, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38657278

RESUMEN

ABSTRACT: There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Donante no Emparentado , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Adolescente , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Estudios Retrospectivos , Adulto Joven , Prueba de Histocompatibilidad , Ciclofosfamida/uso terapéutico , Factores de Edad , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/inmunología , Supervivencia sin Enfermedad
16.
Bone Marrow Transplant ; 59(7): 974-982, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38521885

RESUMEN

This study investigates the interaction between endothelial activation, indirectly measured using EASIX, and the probability of presenting cardiac adverse events (CAE) during the first year after allo-HCT. The 437 consecutive adults undergoing PB allo-HCT from 2012 and 2021 were included. EASIX was retrospectively calculated before and during the first 6 months after allo-HCT and transformed to log2-base to conduct the statistical analysis. The median age was 53, 46 (10.5%) patients had previous history of cardiac disease, MAC allo-HCTs were performed in 186 (42.6%) patients, and PTCY was administered in 242 (55.5%). The 1-year incidence of CAE was 12.6% (n = 55). The most prevalent cardiac events were heart failure and arrhythmias, 32.7% and 23.6% respectively, and the day +100 mortality rate of these patients was 40.5%. During the first 6 months after allo-HCT, EASIX trends were significantly higher in patients who developed CAE. Regression analyses confirmed that higher log2-EASIX values were predictors for higher risk for CAE during the first year after allo-HCT. This analysis identifies a significant association between higher endothelial activation, indirectly measured using EASIX, and higher risk for cardiac toxicity diagnosed during the first year after allo-HCT and extends the applicability of EASIX for identifying patients at risk for CAE.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Adulto , Estudios Retrospectivos , Anciano , Cardiopatías/etiología , Trasplante Homólogo/efectos adversos
18.
EClinicalMedicine ; 69: 102476, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38361991

RESUMEN

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

19.
Ann Hematol ; 103(2): 609-621, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37957371

RESUMEN

Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease.


Asunto(s)
Acetatos , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Adulto , Humanos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Citomegalovirus , Antivirales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos
20.
Transplant Cell Ther ; 30(2): 187.e1-187.e12, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38000709

RESUMEN

Plasma biomarkers of endothelial dysfunction have been postulated for the diagnosis and prognosis of acute graft-versus-host disease (aGVHD). However, their use is not validated in clinical practice yet. The endothelial activation and stress index (EASIX), a simple score based on routine laboratory parameters, is considered to be an indirect marker of endothelial damage. High value of EASIX was correlated with worse non-relapse mortality (NRM) and overall survival (OS) and a high risk of sinusoidal obstructive syndrome and transplant-associated thrombotic microangiopathy (TA-TMA). This study investigates the predictive value of plasma biomarkers and the EASIX score for the prediction of aGVHD. We assessed vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor receptor 1 (TNFR1), and VWF:Ag plasma levels and the EASIX score before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and on days 0, 3, 7, 14, and 21 in an experimental cohort (n = 33). EASIX was transformed to a base-2 logarithm to perform the analysis. For the most relevant biomarkers, we estimate the optimal cutoff values and the discriminatory ability to differentiate patients with high-risk of aGVHD. The conclusions obtained in the experimental cohort were validated in a large cohort of 321 patients at the same institution. Plasma biomarkers and EASIX showed similar post-transplantation dynamics consisting of a progressive increase. Multivariate analysis showed an association between high TNFR1 levels and Log-2 EASIX score on day 7 after transplantation with an increased likelihood of developing aGVHD (hazard ratio [HR] = 1, P = .002; HR = 2.31, P = .013, respectively). Patients with TNFR1 ≥1300 ng/mL (HR = 7.19, P = .006) and Log2-EASIX ≥3 (HR = 14.7, P <.001) at day 7 after transplantation were more likely to develop aGVHD with high predictive accuracy (C-index of 74% and 81%, respectively). In the validation cohort, patients with Log2-EASIX ≥3 on day 7 after transplantation presented a significantly higher incidence of grade II-IV aGVHD (HR = 1.94, P = .004) independent of GVHD prophylaxis (HR = 0.38, P = .004), conditioning regimen (HR = 0.59, P =.02) and type of donor (HR = 2.38, P = .014). Differential degree of endothelial damage can be measured using both EASIX score and plasma biomarkers in the early post-transplantation period. Patients at risk of developing aGVHD could be easily identified by a high EASIX score. Both indicators of endothelial activation represent a promising approach to predict aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Receptores Tipo I de Factores de Necrosis Tumoral , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Biomarcadores
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