RESUMEN

CD54 and CD58 are adhesion proteins that mediate efficient immune synapse formation. Hammer et al. now show that the abrogation of these molecules in T and NK cells prevents their immune rejection while maintaining their effector function. These findings should significantly help advance our efforts to generate "off-the-shelf" allogeneic products.

Asunto(s)

Células Asesinas Naturales , Humanos , Células Asesinas Naturales/inmunología , Trasplante Homólogo , Antígenos CD58/metabolismo , Antígenos CD58/inmunología , Linfocitos T/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos

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

BACKGROUND: Ischemia-reperfusion injury (IRI) is a phenomenon that affects transplant survival. The aim of our study was to examine the effects of IRI in isogenic and allogeneic muscle and skin transplantation models exposed to prolonged warm ischemia. METHODS: Forty-eight Lewis rats and 16 Brown-Norway rats were used to create four groups: Isogenic Inguinal Flap Transplantation (IST), Isogenic Gastrocnemius Muscle Flap Transplantation (IMT), Allogeneic Inguinal Flap Transplantation (AST), and Allogeneic Gastrocnemius Muscle Flap Transplantation (AMT). Malonyldialdehyde (MDA) and superoxide dismutase (SOD) levels were measured on postoperative days 1, 7, 21, 35, 63, 100, and 120 in all groups. Donor-specific chimerism (DSC) in peripheral blood was evaluated in the allogeneic groups on postoperative days 7, 21, 35, 63, 100, and 120. The microRNA-21 and microRNA-205 levels were evaluated on postoperative days 1, 7, and 120 in all groups. At the end of the study, a histopathological examination was performed. RESULTS: A statistically significant difference was found between the groups in terms of MDA and SOD levels. DSC was detected in the AMT group. A significant increase in microRNA-205 was observed, especially in the AMT group. There was no significant difference in the number of functional muscle units between the muscle transplantation groups. CONCLUSION: The presence of DSC in the AMT group and the lack of a significant difference in the number of functional muscle units in the IMT and AMT groups are noteworthy findings.

Asunto(s)

Ratas Endogámicas Lew , Daño por Reperfusión , Trasplante de Piel , Animales , Daño por Reperfusión/patología , Ratas , Masculino , Músculo Esquelético/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguínea , Modelos Animales de Enfermedad , Trasplante Homólogo , Ratas Endogámicas BN

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

Background: Islet transplantation is a promising treatment for type 1 diabetes that aims to restore insulin production and improve glucose control, but long-term graft survival remains a challenge due to immune rejection. Methods: ScRNA-seq data from syngeneic and allogeneic islet transplantation grafts were obtained from GSE198865. Seurat was used for filtering and clustering, and UMAP was used for dimension reduction. Differentially expressed genes were analyzed between syngeneic and allogeneic islet transplantation grafts. Gene set variation analysis (GSVA) was performed on the HALLMARK gene sets from MSigDB. Monocle 2 was used to reconstruct differentiation trajectories, and cytokine signature enrichment analysis was used to compare cytokine responses between syngeneic and allogeneic grafts. Results: Three distinct macrophage clusters (Mø-C1, Mø-C2, and Mø-C3) were identified, revealing complex interactions and regulatory mechanisms within macrophage populations. The significant activation of macrophages in allogeneic transplants was marked by the upregulation of allograft rejection-related genes and pathways involved in inflammatory and interferon responses. GSVA revealed eight pathways significantly upregulated in the Mø-C2 cluster. Trajectory analysis revealed that Mø-C3 serves as a common progenitor, branching into Mø-C1 and Mø-C2. Cytokine signature enrichment analysis revealed significant differences in cytokine responses, highlighting the distinct immunological environments created by syngeneic and allogeneic grafts. Conclusion: This study significantly advances the understanding of macrophage roles within the context of islet transplantation by revealing the interactions between immune pathways and cellular fate processes. The findings highlight potential therapeutic targets for enhancing graft survival and function, emphasizing the importance of understanding the immunological aspects of transplant acceptance and longevity.

Asunto(s)

Rechazo de Injerto , Trasplante de Islotes Pancreáticos , Macrófagos , Análisis de la Célula Individual , Trasplante de Islotes Pancreáticos/inmunología , Trasplante de Islotes Pancreáticos/métodos , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Rechazo de Injerto/inmunología , Ratones , Citocinas/metabolismo , Supervivencia de Injerto/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/cirugía , Trasplante Homólogo , Perfilación de la Expresión Génica , Activación de Macrófagos/genética , Transcriptoma

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

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

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

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

RESUMEN

Despite low incidence, neuroblastoma, an immunologically cold tumor, is the most common extracranial solid neoplasm in pediatrics. In relapsed/refractory cases, the benefits of autologous hematopoietic stem cell transplantation (auto-HSCT) and other therapies are limited. Natural killer (NK) cells apply cytotoxicity against tumor cells independently of antigen-presenting cells and the adaptive immune system. The primary endpoint of this trial was to assess the safety of the injection of allogenic, ex vivo-expanded and primed NK cells in relapsed/refractory neuroblastoma patients after auto-HSCT. The secondary endpoint included the efficacy of this intervention in controlling tumors. NK cells were isolated and primed ex vivo (by adding interleukin [IL]-2, IL-15, and IL-21) in a GMP-compliant CliniMACS system and administered to four patients with relapsed/refractory MYCN-positive neuroblastoma. NK cell injections (1 and 5 × 107 cells/kg in the first and second injections, respectively) were safe, and no acute or sub-acute adverse events were observed. During the follow-up period, one complete response (CR) and one partial response (PR) were observed, while two cases exhibited progressive disease (PD). In follow-up evaluations, two died due to disease progression, including the case with a PR. The patient with CR had regular growth at the 31-month follow-up, and another patient with PD is still alive and receiving chemotherapies 20 months after therapy. This therapy is an appealing and feasible approach for managing refractory neuroblastomas post-HSCT. Further studies are needed to explore its efficacy with higher doses and more frequent administrations for high-risk neuroblastomas and other immunologically cold tumors.Trial registration number: irct.behdasht.gov.ir (Iranian Registry of Clinical Trials, No. IRCT20201202049568N1).

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales , Recurrencia Local de Neoplasia , Neuroblastoma , Trasplante Autólogo , Humanos , Neuroblastoma/terapia , Neuroblastoma/inmunología , Neuroblastoma/patología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Masculino , Preescolar , Recurrencia Local de Neoplasia/terapia , Niño , Resultado del Tratamiento , Trasplante Homólogo

RESUMEN

BACKGROUND: IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes. METHODS: We retrospectively analyzed patients with IL10RA deficiency in Japan. RESULTS: Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status. CONCLUSION: In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250).

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Japón , Masculino , Femenino , Lactante , Resultado del Tratamiento , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Adolescente , Preescolar , Subunidad alfa del Receptor de Interleucina-10/genética , Subunidad alfa del Receptor de Interleucina-10/deficiencia , Niño , Enfermedades Inflamatorias del Intestino/terapia

RESUMEN

BACKGROUND: Assessing multidisciplinary prehabilitation strategies becomes crucial to pre-emptively counter the physical, psychological and social negative impacts experienced during an allogenic haematopoietic stem cell transplant (allo-HSCT) among acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Current evidence is restricted to studies during induction chemotherapy, omitting rehabilitation interventions and predominantly using exercise-only approaches without a multidisciplinary framework. The aim of this study is to investigate the feasibility, safety and preliminary efficacy of multidisciplinary prehabilitation in adults offered allo-HSCT. METHODS AND ANALYSIS: This 8-week single-group pre-post feasibility study aims to pilot a multidisciplinary prehabilitation intervention for participants undergoing allo-HSCT, with a focus on feasibility and safety. Participants, aged 18 or older, diagnosed with AML or MDS, and offered allo-HSCT, will be recruited between June 2023 and July 2024. The multidisciplinary prehabilitation intervention, conducted by the cancer allied health team at the Royal Adelaide Hospital, includes exercise physiology, physiotherapy, dietetics, social work, occupational therapy and psychology interventions. Consistent with a multidisciplinary treatment approach, each component is tailored to address different aspects of patient care, and adherence calculations will assess patient engagement and compliance. In addition, participants will continue to receive usual care from cancer allied health staff. The primary outcome of the study is to assess the feasibility of a multidisciplinary prehabilitation intervention by evaluating intervention uptake, retention, adherence, acceptability and safety. Secondary outcomes are leg strength, upper-body strength, aerobic fitness, falls risk, anthropometry, nutritional status, quality of life, anxiety, depression, self-efficacy for coping with cancer and distress. ETHICS AND DISSEMINATION: Ethics approval for this study has been provided by the Central Adelaide Local Health Network (HREC 2022/HRE00284). Recruitment for the study commenced in June 2023 and will continue until July 2024. The methods have been designed and are reported according to the SPIRIT and CONSORT-pilot study checklist. TRIAL REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000052639.

Asunto(s)

Estudios de Factibilidad , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Ejercicio Preoperatorio , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/rehabilitación , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/rehabilitación , Calidad de Vida , Proyectos Piloto , Adulto , Trasplante Homólogo

RESUMEN

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by air accumulation within the subserosa or submucosa of the gastrointestinal wall. We herein report a case involving a woman in her early 30s who developed PCI after undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. The patient had a history of multiple COVID-19 infections. Imaging revealed extensive pneumoperitoneum and mesenteric emphysema; nevertheless, the patient remained clinically stable with a benign abdominal examination. She eventually recovered after 1 month of conservative treatment. We believe the PCI in this case had a multifactorial etiology, potentially involving both HSCT and COVID-19. Raising awareness of PCI may help avoid unnecessary surgical interventions and associated morbidity.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Neumatosis Cistoide Intestinal , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Neumatosis Cistoide Intestinal/etiología , Neumatosis Cistoide Intestinal/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adulto , COVID-19/complicaciones , Tomografía Computarizada por Rayos X , SARS-CoV-2 , Trasplante Homólogo/efectos adversos

RESUMEN

Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.

Asunto(s)

Citocinas , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Citocinas/genética , Adulto , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/etiología , Persona de Mediana Edad , Trasplante Homólogo/efectos adversos , Adulto Joven , Adolescente , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidad , Antígenos HLA/genética , Antígenos HLA/inmunología , Polimorfismo Genético , Anciano

RESUMEN

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Asunto(s)

Insuficiencia Pancreática Exocrina , Trasplante de Células Madre Hematopoyéticas , Lipomatosis , Síndrome de Shwachman-Diamond , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Adulto , Insuficiencia Pancreática Exocrina/terapia , Trasplante Homólogo , Enfermedades de la Médula Ósea/terapia , Mutación

Asunto(s)

Anticuerpos Monoclonales , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Masculino , Trasplante Homólogo , Adulto

RESUMEN

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Asunto(s)

Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores , Recurrencia , Humanos , Anemia Aplásica/terapia , Anemia Aplásica/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adolescente , Adulto , Enfermedad Injerto contra Huésped/etiología , Niño , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Adulto Joven , Preescolar , Persona de Mediana Edad , Resultado del Tratamiento , Suero Antilinfocítico/uso terapéutico , Suero Antilinfocítico/administración & dosificación , Trasplante Homólogo , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Terapia de Inmunosupresión/métodos , Estudios Retrospectivos , Ciclosporina/uso terapéutico , Ciclosporina/administración & dosificación