RESUMEN

RATIONALE: Fanconi anemia (FA) is a hereditary disease caused by mutations in the genes involved in the DNA damage repair pathway. The FANCA gene is the most commonly pathogenic gene, accounting for more than 60% of all causative genes. PATIENT CONCERNS: The clinical case is a 3-year-old boy showed mild anemia and scattered bleeding spots the size of a needle tip all over his body. DIAGNOSES: Compound heterozygous mutation was identified in the FANCA gene in the FA case: c.1A > T from the father in exon 1; the deletion of chr16: 89857810-89858476 (exon13-14 del) from the mother; finally, the patient was diagnosed as Fanconi anemia. INTERVENTION: After diagnosis, the child received chemotherapy (Ara-C + Flu + Cy + ATG). Then, the hematopoietic stem cell transplantation and unrelated umbilical cord blood transfusion were performed. OUTCOMES: The child is recovering well and is in regular follow-up. CONCLUSION AND LESSONS: The discovery of new mutations in the FANCA gene enriches the genetic profile of FA and helps clinicians to further understand this disease and guide genetic counseling and prenatal diagnosis. Whole-exome sequencing is a powerful tool for diagnosing FA.

Asunto(s)

Proteína del Grupo de Complementación A de la Anemia de Fanconi , Anemia de Fanconi , Humanos , Anemia de Fanconi/genética , Anemia de Fanconi/complicaciones , Anemia de Fanconi/diagnóstico , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Masculino , Preescolar , Mutación , Trasplante de Células Madre Hematopoyéticas

RESUMEN

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/terapia , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Rituximab/uso terapéutico , Trasplante Homólogo/efectos adversos

RESUMEN

We present an unusual etiology of primary renal allograft dysfunction attributed to myeloma cast nephropathy in a patient with no history of multiple myeloma before kidney transplant. The patient, a 54-year-old woman, had been on hemodialysis for 6 months before transplant for presumed diabetic nephropathy; she developed graft dysfunction immediately after transplant. Graft biopsy specimens were consistent with myeloma cast nephropathy, and she was treated with bortezomib, cyclophosphamide, and dexamethasone. She achieved a complete hematological response and regained excellent graft function 3 months after transplant. The patient then received autologous stem cell transplant 8 months after kidney transplant. To our knowledge, this is the second report of a successful graft outcome after chemotherapy and the first report treated with autologous stem cell transplantation after remission of monoclonal disease.

Asunto(s)

Trasplante de Riñón , Mieloma Múltiple , Disfunción Primaria del Injerto , Humanos , Trasplante de Riñón/efectos adversos , Femenino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Resultado del Tratamiento , Biopsia , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/fisiopatología , Inmunosupresores/efectos adversos , Diagnóstico Erróneo , Aloinjertos , Trasplante Autólogo , Factores de Tiempo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos

RESUMEN

OBJECTIVES: During and after allogeneic hematopoietic stem cell donation, donors may experience adverse events. This situation can increase anxiety of candidate donors. Time to return to daily life routine and work, presentation of comorbid diseases in follow-up, and donor opinions are topics of interest. MATERIALS AND METHODS: We conducted a 14-question survey among related stem cell donors between January 2010 and March 2019 by telephone interview. RESULTS: Of 257 related donors, 175 (68.1%) were interviewed; 87 (49.7%) were female and 88 (50.3%) were male. Among donors interviewed, 144 (82.3%) donated from only peripheral blood. After harvesting of stem cells, adverse events included hip pain (38.7%), bone pain (57.2%) during mobilization, and paresthesia (28.9%) during apheresis. After apheresis, 2 serious adverse events were reported in 2 (1.3%) female donors (1 salpingo-oophorectomy and 1 nephrectomy). Splenomegaly was observed in 1 male donor (0.7%). Among donors interviewed, 77 (44%) reported being able to perform daily activities on the same day. The shortest time to daily activity was in the peripheral blood group, and the longest was in the bone marrow group (P = .001). Among working donors, 23 (27.4%) returned to work on the same day; all were peripheral blood donors. Among donors interviewed, 114 (65.1%) wanted to volunteer to donate again. One donor (0.6%) expressed guilt after donation, and 162 (92.6%) recommended other people to be stem cell donors. During the follow-up period, musculoskeletal-joint diseases increased after donation (P = .012). CONCLUSIONS: It is important to raise awareness in society about stem cell donation and to reduce the concerns among donor candidates. Although most of the adverse events after donation are temporary and mild, a few serious adverse events in donors have been observed. Stem cell donation does not cause loss of daily activity or inability to return to the work force.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Humanos , Femenino , Masculino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/psicología , Factores de Tiempo , Adulto , Persona de Mediana Edad , Factores de Riesgo , Trasplante Homólogo , Reinserción al Trabajo , Adulto Joven , Actividades Cotidianas , Resultado del Tratamiento , Entrevistas como Asunto , Donadores Vivos , Teléfono

RESUMEN

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22.1 to 2.1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23.5 days (p = 0.002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0.057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0.78). Our retrospective results indicate that FFP2 masks worn by patients and hospital staff may help to significantly reduce the incidence of viral respiratory infections, including COVID-19, shorten the in-hospital time, and reduce costs without affecting survival.

Asunto(s)

COVID-19 , Trasplante de Células Madre Hematopoyéticas , Máscaras , Infecciones del Sistema Respiratorio , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Adulto , Trasplante Homólogo/efectos adversos , Anciano , SARS-CoV-2/aislamiento & purificación , Incidencia

RESUMEN

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft-versus-host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open-label, dose-finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo-HSCT were analyzed using a two-compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time-varying covariates. Model selection was driven by goodness-of-fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo-HSCT, vedolizumab PK were well described by a two-compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Modelos Biológicos , Trasplante Homólogo , Humanos , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Adulto , Enfermedad Injerto contra Huésped/prevención & control , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Anciano , Adolescente , Fármacos Gastrointestinales/farmacocinética , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/administración & dosificación , Relación Dosis-Respuesta a Droga

RESUMEN

The annual number of human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) is increasing steadily. Comparative studies about haplo-HCT versus HCT with HLA-matched sibling donors (MSD-HCT) have been tried in acute myeloid leukemia and B-cell acute lymphoblastic leukemia/lymphoma (ALL). Few studies were reported in adult T-cell ALL (T-ALL). In this retrospective study, a total of 88 consecutive patients with T-ALL were enrolled who underwent MSD-HCT (n = 24) and haplo-HCT (n = 64) with antithymocyte globulin (ATG)-based graft versus host disease (GVHD) prophylaxis between 2010 and 2022. Median follow-up for survivors was similar (43.5 [range: 7-88] months for MSD-HCT versus 43.5 (range: 6-144) months in the Haplo-HCT group). The 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD) was similar, 33% (95% confidence interval [CI], 16%-52%) after MSD-HCT versus 44% (95% CI, 31%-55%) after haplo-HCT, P = 0.52. The cumulative incidences of grade III-IV aGVHD were 8% (95% CI, 1%-23%) in the MSD-HCT group and 5% (95% CI, 1%-12%) in the haplo-HCT group (P = 0.50). The 2-year cumulative incidence of chronic GVHD (limited and extensive) in the haplo-HCT, 11% (95% CI, 5%-20%) was significantly lower than that in the MSD-HCT group (42% [95% CI, 21%-62%], P = 0.002). The cumulative incidence of 4-year relapse rates (44% versus 37%, P = 0.56) and non-relapse mortality (7% versus 21%, P = 0.08) did not differ between these two groups. There were also no differences in 4-year overall survival (46% versus 47%, P = 0.44) and progression-free survival (49% versus 42%, P = 0.45) between these two groups. On multivariate analysis, using busulfan/fludarabine (BU/Flu) conditioning regimen was found to be associated with worse clinical outcome. Our results suggested that ATG-based haplo-HCT platform could work as an alternative to MSD-HCT for adult patients with T-ALL. Compared with MSD-HCT, haplo-HCT might carry a low risk for cGVHD.

Asunto(s)

Suero Antilinfocítico , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hermanos , Humanos , Adulto , Femenino , Masculino , Suero Antilinfocítico/uso terapéutico , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto Joven , Estudios Retrospectivos , Trasplante Haploidéntico/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Enfermedad Crónica

RESUMEN

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.

Asunto(s)

Aclarubicina , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad Injerto contra Huésped , Factor Estimulante de Colonias de Granulocitos , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Aclarubicina/uso terapéutico , Aclarubicina/administración & dosificación , Adulto Joven , Citarabina/uso terapéutico , Citarabina/administración & dosificación , Idarrubicina/administración & dosificación , Idarrubicina/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adolescente , Resultado del Tratamiento , Recurrencia , Anciano

RESUMEN

Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HEDclass I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.

Asunto(s)

Selección de Donante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Masculino , Femenino , Adulto , Adolescente , Persona de Mediana Edad , Niño , Estudios Retrospectivos , Factores de Riesgo , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/genética , Adulto Joven , Antígenos HLA/genética , Antígenos HLA/inmunología , Preescolar , Trasplante Haploidéntico , Donantes de Tejidos , Evolución Molecular

RESUMEN

PURPOSE: Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. METHODS: A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. RESULTS: Participants aged 25-74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: "Transiting from an external obligation to a habit"; "Being in the middle between the negative and positive effects of the IMMs"; "Failure to systematically respect the rules"; and "Adopting personal strategies to become adherent". After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. CONCLUSIONS: MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients' MA to IMMs.

Asunto(s)

Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores , Cumplimiento de la Medicación , Investigación Cualitativa , Humanos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/psicología , Persona de Mediana Edad , Masculino , Femenino , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Anciano , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Enfermedad Aguda , Administración Oral , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Factor de Transcripción STAT1 , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Masculino , Femenino

RESUMEN

INTRODUCTION/AIM: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients. METHODS: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases. RESULTS: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed. CONCLUSION: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT.

Asunto(s)

Suplementos Dietéticos , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Deficiencia de Vitamina D , Vitamina D , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/sangre , Vitamina D/sangre , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/sangre , Femenino , Incidencia , Masculino

RESUMEN

Clinical data of 1 494 patients with hematological diseases who were scheduled to receive allogeneic hematopoietic stem cell transplantation and received the anti-human-leukocyte-antigen (HLA) antibody test for the first time at the First Affiliated Hospital of Soochow University from 2016 to 2018 was collected to analyze the positive rates and distribution characteristics of different types of pre-existing anti-HLA antibodies in patients with different hematological diseases. Among 1 494 patients with hematological diseases, there were 849 males and 645 females, aged [31 (17, 45)] years, and included 577 cases of acute myeloid leukemia (AML), 373 cases of acute lymphocytic leukemia (ALL), 234 cases of aplastic anemia (AA), 175 cases of myelodysplastic syndrome (MDS), and 135 cases of other diseases. The total positive rate of pre-existing anti-HLA antibodies was 25.1% (375/1 494), among which the positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies were 11.2% (168/1 494), 4.9% (73/1 494), and 9.0% (134/1 494), respectively.The total positive rates of pre-existing anti-HLA antibodies in patients with MDS、AA、AML、ALL and other diseases were 40.6% (71/175), 30.8% (72/234), 26.2% (151/577), 12.3% (46/373), and 25.9% (35/135), respectively, with statistically significant difference (P<0.001). The positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies in patients with different hematological diseases showed statistically significant differences (all P<0.001). Given the varying positive rates and distribution characteristics of pre-existing anti-HLA antibodies among patients with different hematological diseases, anti-HLA antibody test should be performed before receiving hematopoietic stem cell transplantation.

Asunto(s)

Anemia Aplásica , Antígenos HLA , Enfermedades Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Síndromes Mielodisplásicos/inmunología , Adolescente , Antígenos HLA/inmunología , Enfermedades Hematológicas/inmunología , Adulto Joven , Anemia Aplásica/inmunología , Leucemia Mieloide Aguda/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Trasplante Homólogo

RESUMEN

The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been studied to advance the treatment of neurodegenerative disorders. Here, we explored the transplantation efficacy of different cell subsets and delivery routes with the goal of favoring the establishment of a stable and exclusive engraftment of HSPCs and their progeny in the CNS of female mice. In this setting, we show that the CNS environment drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Intra-CNS transplantation of HSPCs engineered to overexpress TREM2 decreased neuroinflammation, Aß aggregation and improved memory in 5xFAD female mice. Our proof of concept study demonstrates the therapeutic potential of HSPC gene therapy for Alzheimer's disease.

Asunto(s)

Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Terapia Genética , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas , Ratones Transgénicos , Microglía , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Terapia Genética/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Ratones , Microglía/metabolismo , Células Madre Hematopoyéticas/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Péptidos beta-Amiloides/metabolismo , Diferenciación Celular , Humanos , Ratones Endogámicos C57BL

Asunto(s)

Células Madre Hematopoyéticas , Macrófagos , Humanos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Macrófagos/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Animales , Comunicación Celular/fisiología

RESUMEN

LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.

Asunto(s)

Busulfano , Trasplante de Células Madre Hematopoyéticas , Tiotepa , Acondicionamiento Pretrasplante , Vidarabina , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Tiotepa/uso terapéutico , Masculino , Femenino , Lactante , Preescolar , Enfermedad Injerto contra Huésped/etiología , Niño , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/terapia

RESUMEN

OBJECTIVE AND BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication in hematopoietic stem cell transplantation (HSCT) patients. However, the related risk factors in pediatric and young adult HSCT recipients remain unclear. Thus, we conducted this meta-analysis to identify potential risk factors for SOS in children and young adults undergoing HSCT. METHOD: We acquired related articles through searching PubMed, EMBASE, and the Cochrane Library up to May 31, 2024. We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to identify potential risk factors. RESULTS: A total of 12 studies with 7644 HSCT recipients were included. Bone marrow transplantation (OR = 1.35, 95% CI: 1.03-1.77, I2 = 0%), busulfan (BU) (OR = 3.63, 95% CI: 1.78-7.38, I2 = 70%), and fludarabine (FLU) (OR = 1.55, 95% CI: 1.09-2.21, I2 = 16%) were risk factors for SOS after HSCT in children and young adults. CONCLUSION: Bone marrow transplantation and the use of BU or FLU might be risk factors for SOS after HSCT in children and young adults.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Humanos , Enfermedad Veno-Oclusiva Hepática/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de Riesgo , Pronóstico , Niño , Adulto Joven , Acondicionamiento Pretrasplante/efectos adversos , Adolescente

RESUMEN

The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

Asunto(s)

Mutación con Ganancia de Función , Trombocitopenia , Proteínas de Unión al GTP rap , Humanos , Masculino , Sustitución de Aminoácidos , Trasplante de Células Madre Hematopoyéticas , Síndromes de Inmunodeficiencia/genética , Mutación Missense , Proteínas de Unión al GTP rap/genética , Proteínas de Unión al GTP rap/metabolismo , Trombocitopenia/genética , Trombocitopenia/patología , Recién Nacido , Lactante , Preescolar , Niño

RESUMEN

BACKGROUND: The aim of this study was to describe salivary flow rate, subjective oral dryness and dental caries 5 years post haematopoietic cell transplantation (HCT). METHODS: HCT survivors of a previous longitudinal observational cohort study in the Netherlands (the H-OME study) were invited to participate in this additional follow-up after 5 years (the HOME2 study). During the additional follow-up appointment, stimulated (SWS) and unstimulated whole saliva (UWS) was collected, participants rated subjective oral dryness on a 0 - 10 scale, and caries lesions were assessed. Furthermore, dental records, including treatments and radiographs, were requested for the 5 years preceding and the 5 years following transplantation. Paired t-tests were performed to determine changes in UWS and SWS flow rates and subjective oral dryness from pre-HCT, and to compare the number of caries-related dental treatments (restorations, endodontic treatments or extractions) before and after HCT. Hyposalivation of UWS (< 0.2 mL/min) and SWS (< 0.7 mL/min) at 3 and 12 months, was used to explore the predictive potential of hyposalivation on a high dental treatment need (> 3 treatments) over the 5 years post-HCT. RESULTS: Five years post-HCT, 39 HCT survivors were included. The mean UWS flow rate was 0.36 mL/min (SD 0.26) and the mean SWS flow rate 1.02 (SD 0.57); survivors were diagnosed with a median of 0 dentine lesions (range 0 - 12) and 73% reported a subjective oral dryness score ≥ 1. Survivors underwent a median of 3 (range 0 - 20) dental treatments during the 5 years following transplantation. The mean difference in UWS 5 years post-HCT compared to pre-HCT was 0.03 (95% CI: -0.07 - 10.12), the mean difference for SWS was -0.18 (95% CI: -0.45 - 0.08) and for subjective oral dryness 1.2 (95% CI: 0.2 - 2.1). In the 5 years post-HCT, non-significantly more treatments were performed compared to the 5 years pre-HCT (mean difference: 0.5, 95%CI: -1.2 - 2.2). Seventy eight percent of patients with hyposalivation of SWS at 12 months had a high dental treatment need, compared with 38% with no hyposalivation. CONCLUSIONS: Five years post-HCT, mean UWS and SWS flow rates were not significantly different from pre-HCT levels but subjective oral dryness scores were elevated.

Asunto(s)

Caries Dental , Trasplante de Células Madre Hematopoyéticas , Xerostomía , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Caries Dental/etiología , Xerostomía/etiología , Xerostomía/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Longitudinales , Saliva/metabolismo , Tasa de Secreción , Países Bajos , Anciano

RESUMEN

Background: Hematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT. Case presentation: A 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted. Conclusion: OTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

Asunto(s)

Criopreservación , Preservación de la Fertilidad , Trasplante de Células Madre Hematopoyéticas , Ovario , Humanos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Ovario/patología , Preservación de la Fertilidad/métodos , Adulto Joven , Rechazo de Injerto/etiología , Trasplante Homólogo , Anemia Aplásica/terapia , Adulto , Reserva Ovárica