RESUMEN
We retrospectively evaluated the effect of 17 individual comorbidities, defined by the hematopoietic cell transplantation (HCT)-specific comorbidity index, on non-relapse mortality (NRM) and overall survival (OS) in 9531 patients aged between 16 and 70 years who underwent their first allogeneic HCT from 8/8 and 7/8 allele-matched unrelated donors (8/8 and 7/8 MUDs) or single-unit unrelated cord blood (UCB) between 2011 and 2020 using data from a Japanese registry database. In the multivariate analysis, infection (adjusted hazard ratio [HR], 1.62, 95% confidence interval [CI], 1.33-1.99 for 8/8 and 7/8 MUDs; adjusted HR, 1.33, 95%CI, 1.12-1.58 for UCB) and moderate/severe hepatic comorbidity (adjusted HR, 1.57, 95%CI, 1.04-2.38 for 8/8 and 7/8 MUDs; adjusted HR, 1.53, 95%CI, 1.09-2.15 for UCB) had a significant impact on NRM in both donor groups. Cardiac comorbidity (adjusted HR, 1.40, 95%CI, 1.08-1.80), mild hepatic comorbidity (adjusted HR, 1.22, 95%CI, 1.01-1.48), rheumatologic comorbidity (adjusted HR, 1.67, 95%CI, 1.11-2.51), renal comorbidity (adjusted HR, 2.44, 95%CI, 1.46-4.09), and severe pulmonary comorbidity (adjusted HR, 1.40, 95%CI, 1.11-1.77) were significantly associated with an increased risk of NRM but only in UCB recipients. Renal comorbidity had the strongest impact on poor OS in both donor groups (adjusted HR, 1.73, 95%CI, 1.10-2.72 for 8/8 and 7/8 MUDs; adjusted HR, 2.24, 95%CI, 1.54-3.24 for UCB). Therefore, unrelated donor selection should be taken into consideration along with the presence of specific comorbidities, such as cardiac, rheumatologic, renal, mild hepatic, and severe pulmonary comorbidities.
Asunto(s)
Artritis Reumatoide , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Donante no Emparentado , Estudios Retrospectivos , Japón , Sangre Fetal , Acondicionamiento Pretrasplante/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , ComorbilidadRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited. We investigated the effect of busulfan dose on outcomes by comparing Flu/Bu2 and Flu/Bu4 in patients with NHL who underwent allogeneic HCT. Our study included 415 adult patients with NHL who received Flu/Bu2 (315 patients) or Flu/Bu4 (100 patients) between January 2008 and December 2019. All patients were enrolled in the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The primary endpoint was the 5-year overall survival (OS). To minimize potential confounding factors that may influence outcomes, we performed propensity score matching. The 5-year OS was 50.6% (95% confidence interval (CI), 39.4%-60.8%) and 32.2% (95% CI, 22.4-42.4%) in the Flu/Bu2 and Flu/Bu4 groups, respectively (p = 0.006). The hazard ratio comparing the two groups was 2.13 (95% CI, 1.30-3.50; p = 0.003). Both groups had a similar 5-year cumulative incidence of relapse (38.2% vs 41.3%; p = 0.581), and the Flu/Bu4 group had a higher cumulative incidence of 5-year NRM (15.7% vs 31.9%; p = 0.043). In this study, Flu/Bu4 was associated with worse OS compared with Flu/Bu2 because of high NRM in patients with NHL.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Adulto , Humanos , Busulfano , Enfermedad Injerto contra Huésped/etiología , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma no Hodgkin/etiología , Vidarabina , Acondicionamiento PretrasplanteRESUMEN
The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
To evaluate the long-term efficacy of high-dose dexamethasone (HD-DXM) treatment for immune thrombocytopenia (ITP), we retrospectively analysed 36 newly diagnosed ITP patients treated with HD-DXM as a first-line treatment. An initial response was obtained in 23 (63.9%) patients, including 11 with a complete response (CR) and 12 with a partial response (PR). Six months after HD-DXM treatment, 26 of 33 (78.8%) evaluable patients achieved objective responses, including 18 CR and 8 PR. Among 13 patients without initial response, very early increased platelet count within a week (VEIP) was observed in 7 patients, 5 (71.4%) of whom achieved a response at 6 months. In 29 patients who had available platelet count within a week, patients showing VEIP revealed longer survival than those who did not (p = 0.026). HD-DXM was an effective treatment for newly diagnosed ITP patients. VEIP after HD-DXM treatment initiation was associated with a long-term objective response in newly diagnosed ITP patients.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Dexametasona/uso terapéutico , Humanos , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Little is known about stem cell transplantation in solid organ transplantation (SOT) recipients. We conducted a nationwide retrospective survey of Japan Society for Hematopoietic Stem Cell Transplantation centers. A total of 19 patients who underwent 22 hematopoietic stem cell transplantations (HSCTs) after SOT were identified: 5 autologous HSCTs and 17 allogeneic HSCTs were performed. Patients who underwent autologous HSCT received a liver (nâ¯=â¯4) or kidney (nâ¯=â¯1) transplant. All 5 patients achieved neutrophil engraftment, and 2 of 3 patients with hepatoblastoma were alive at 1 year after HSCT. Allogeneic HSCT was performed in 16 patients (7 liver transplant recipients and 9 kidney transplant recipients). Among these, 2 donors were identical for both transplantations. All but 1 patient achieved neutrophil engraftment. The 5-year overall survival rate was 41.7%, but that in patients with malignant disease (nâ¯=â¯13) was much lower than the overall rate (23.1%). Only 1 patient with malignant disease underwent allogeneic HSCT in nonremission. In allogeneic HSCT after kidney transplantation, post-transplantation (1 year) kidney function in 5 evaluable patients was significantly lower than that before allogeneic HSCT, and 3 patients experienced renal rejection. However, no severe hepatic rejection was noted. In SOT recipients, HSCT is a potentially curable treatment for hematologic disorders, but it must be performed with caution, especially in patients with malignancy.
Asunto(s)
Rechazo de Injerto , Trasplante de Células Madre Hematopoyéticas , Trasplante de Riñón , Trasplante de Hígado , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Rechazo de Injerto/mortalidad , Rechazo de Injerto/prevención & control , Humanos , Lactante , Japón/epidemiología , Masculino , Persona de Mediana Edad , Sociedades Médicas , Tasa de Supervivencia , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The effects of cytomegalovirus (CMV) reactivation on cord blood transplant (CBT) are unclear. We assessed the effect of CMV reactivation in adult single-unit CBT without in vivo T cell depletion. Of 3147 eligible cases, 2052 were acute myeloid leukemia (AML), 643 acute lymphoblastic leukemia (ALL), and 452 myelodysplastic syndrome (MDS). CMV reactivation up to 100 days after CBT was associated with better overall survival (OS) compared with no reactivation cases (57.3% versus 52.6% at 3 years after CBT), whereas nonrelapse mortality (NRM) was increased in ALL (16.2% versus 8.9%) and standard disease risk (17.1% versus 10.6%, P = .014) by CMV reactivation. On multivariate analysis, CMV reactivation had favorable effects on relapse in MDS (hazard ratio [HR], .55; P = .044) and high disease risk (HR, .77; P = .047). In NRM, only standard-risk cases showed adverse effects of CMV reactivation (HR, 1.56; P = .026). OS was significantly improved with CMV reactivation in a subgroup of patients with AML (HR, .84; P = .044), MDS (HR, .68; P = .048), and high disease risk (HR, .81; P = .013). This favorable effect of CMV reactivation on OS in AML and high disease risk cases was maintained even after considering the effect of grades II to IV acute graft-versus-host disease. Thus, CMV reactivation might have beneficial or adverse effects on relapse, NRM, and OS, depending on the disease type or disease risk.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Activación Viral , Adulto , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Citomegalovirus , Humanos , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registry database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between 2006 and 2013 from an 8/8 HLA-matched unrelated bone marrow donor (MUD, n = 1367), an HLA-mismatched unrelated bone marrow donor (MMUD, n = 1102), or unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into five groups: High-TBI-(>8Gy), Low-TBI- (≤8Gy), and no-TBI-myeloablative conditioning (MAC), and Low-TBI- and no-TBI-reduced-intensity conditioning (RIC). In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five conditioning groups, and TBI was not associated with prompt neutrophil engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a higher rate of day-30 neutrophil engraftment than no-TBI-regimens: 78% in High-TBI-MAC, 83% in Low-TBI-MAC, and 76% in Low-TBI-RIC versus 65% in No-TBI-MAC, and 68% in No-TBI-RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI-regimens were significantly associated with a higher rate of neutrophil engraftment. Subsequently focusing on CBT patients alone, TBI-regimens were significantly associated with a higher rate of neutrophil engraftment in patients who received CBT with a 4/6 or less HLA allele-match, or who had anti-HLA antibodies. In summary, TBI-regimens had no impact on neutrophil engraftment in the current practice of unrelated bone marrow transplantation. However, in CBT, TBI is still necessary to enhance engraftment.
Asunto(s)
Médula Ósea/inmunología , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Histocompatibilidad/inmunología , Leucemia/terapia , Neutrófilos , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total/métodos , Adolescente , Adulto , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia/mortalidad , Leucemia/radioterapia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Neutrófilos/inmunología , Neutrófilos/efectos de la radiación , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Donantes de Tejidos , Adulto JovenRESUMEN
Ecotropic viral integration site 1 (Evi1) is one of the master regulators in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome. High expression of Evi1 is found in 10% of patients with AML and indicates a poor outcome. Several recent studies have indicated that Evi1 requires collaborative factors to induce AML. Therefore, the search for candidate factors that collaborate with Evi1 in leukemogenesis is one of the key issues in uncovering the mechanism of Evi1-related leukemia. Previously, we succeeded in making a mouse model of Evi1-related leukemia using a bone marrow transplantation (BMT) system. In the Evi1-induced leukemic cells, we identified frequent retroviral integrations near the CCAAT/enhancer-binding protein ß (C/EBPß) gene and overexpression of its protein. These findings imply that C/EBPß is a candidate gene that collaborates with Evi1 in leukemogenesis. Cotransduction of Evi1 and the shortest isoform of C/EBPß, liver inhibitory protein (LIP), induced AML with short latencies in a mouse BMT model. Overexpression of LIP alone also induced AML with longer latencies. However, excision of all 3 isoforms of C/EBPß (LAP*/LAP/LIP) did not inhibit the development of Evi1-induced leukemia. Therefore, isoform-specific intervention that targets LIP is required when we consider C/EBPß as a therapeutic target.
Asunto(s)
Trasplante de Médula Ósea , Proteína beta Potenciadora de Unión a CCAAT/fisiología , Transformación Celular Neoplásica/genética , Proteínas de Unión al ADN/fisiología , Leucemia Mieloide Aguda/genética , Proto-Oncogenes/fisiología , Factores de Transcripción/fisiología , Animales , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/patología , Proteína beta Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Células Cultivadas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Regulación Leucémica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/patología , Proteína del Locus del Complejo MDS1 y EV11 , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Biológicos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiología , Proto-Oncogenes/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
While most studies regarding reactive oxygen species (ROS) focus on their deleterious biological effects, a growing body of evidence indicates the importance of ROS as critical mediators of several signaling pathways, including those involved in hematopoiesis. In this study, we show the critical role of ROS in lineage decision of myeloid progenitors. In megakaryocyte-erythrocyte progenitor cells (MEP), intracellular ROS levels were found to be as low as those in hematopoietic stem cells (HSC). In contrast, remarkably high intracellular ROS levels were observed in granulocyte-monocyte progenitor cells. Intracellular ROS levels in common myeloid progenitors (CMP) were inversely correlated with their MEP differentiation potential. Moreover, gene set enrichment analysis revealed that ROS-low CMP showed gene expression patterns similar to those of MEP, indicating that intracellular ROS levels mark the fate of CMP. In in vitro assays, ROS significantly suppressed the generation of MEP and the formation of megakaryocyte-erythrocyte colonies from CMP. In ROS-high CMP, expression of colony-stimulating factor one receptor (CSF1R) was highly upregulated, and its surface expression correlated with their granulocyte-monocyte differentiation potential. Furthermore, ROS was found to induce the expression of CSF1R mRNA in a leukemia cell line. These data provide novel insights into the relationship between ROS and the hematopoietic differentiation system.
Asunto(s)
Diferenciación Celular/genética , Eritrocitos/citología , Megacariocitos/citología , Especies Reactivas de Oxígeno/metabolismo , Células de la Médula Ósea/citología , Eritrocitos/metabolismo , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Humanos , Megacariocitos/metabolismo , Monocitos/citología , Células Mieloides/citología , Receptor de Factor Estimulante de Colonias de Macrófagos/genéticaRESUMEN
OBJECTIVE: Levofloxacin is widely used as antimicrobial prophylaxis against high-risk chemotherapy-induced neutropenia. Garenoxacin, a fluoroquinolone developed in Japan, shows a stronger in vitro antimicrobial activity against Gram-positive bacteria than levofloxacin. METHODS: We retrospectively analyzed high-risk patients with acute myeloid leukemia who were administered garenoxacin (n = 36) or levofloxacin (n = 120) during chemotherapy. We compared the profiles of infections between these fluoroquinolones. RESULTS: Febrile events occurred in 31 (86%) and 93 (78%) cases in the garenoxacin and levofloxacin group, respectively (P = 0.35). Bloodstream infections by Gram-positive bacteria were recorded in one (3%) case in the garenoxacin group and 25 (21%) cases in the levofloxacin group (P < 0.01). In contrast, bloodstream infections by Gram-negative microorganisms were identified in five (4%) cases in the levofloxacin group and eight (22%) cases in the garenoxacin group (P < 0.01). CONCLUSIONS: These results indicate that there may be substantial differences in the antimicrobial spectrum between different fluoroquinolones. Although there are several biases due to rather small sample size and the retrospective nature, we should take the differences into consideration when we administer a prophylactic fluoroquinolone to a patient with hematological disease.
Asunto(s)
Antibacterianos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/prevención & control , Neutropenia Febril/tratamiento farmacológico , Fluoroquinolonas/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Levofloxacino/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bacteriemia/epidemiología , Bacteriemia/prevención & control , Neutropenia Febril/etiología , Neutropenia Febril/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevención Primaria/métodos , Estudios Retrospectivos , Tamaño de la MuestraRESUMEN
Currently, we utilize vitamins and trace elements formulations that are not prepared specifically for patients receiving hematopoietic stem cell transplantation (HSCT), and adequacy of this strategy has not been evaluated. We prospectively measured blood level of vitamins and trace elements in 15 patients once per week at 6 time points around the acute phase of allogeneic HSCT. We provided standard nutrition support, including administration of parenteral nutrition with vitamin and trace elements formulation in case of impairment of oral intake. Most patients had vitamin B1 deficiency from the start of preparative regimens. Vitamin C deficiency was prominent throughout the acute phase of HSCT and this was significantly associated with high inflammatory markers, C-reactive protein and ferritin. Remarkable vitamin K overload associated with administration of parenteral supplementation and ferritin overload caused by repeated transfusions was observed. Moderate deficiency of zinc was at least partially linked to gastrointestinal loss by diarrhea. We revealed several features of vitamin and trace element status in the acute phase of HSCT and provided a basis for attempts to improve the nutritional condition in HSCT recipients.
Asunto(s)
Ácido Ascórbico/sangre , Neoplasias Hematológicas/sangre , Trasplante de Células Madre Hematopoyéticas , Tiamina/sangre , Oligoelementos/sangre , Vitamina K/sangre , Adulto , Anciano , Ácido Ascórbico/administración & dosificación , Proteína C-Reactiva/metabolismo , Femenino , Ferritinas/sangre , Ferritinas/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Tiamina/administración & dosificación , Oligoelementos/administración & dosificación , Acondicionamiento Pretrasplante , Trasplante Homólogo , Vitamina K/administración & dosificaciónAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Herpes Zóster/mortalidad , Anciano , Autoinjertos , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Femenino , Estudios de Seguimiento , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Humanos , Melfalán/administración & dosificación , Persona de Mediana Edad , Podofilotoxina/administración & dosificaciónRESUMEN
The requirement of antifungal prophylaxis has not been established in the chemotherapies for malignant lymphoma. This study was conducted to explore the incidence of invasive fungal diseases (IFD) and their risk factors in patients receiving salvage therapies for malignant lymphoma. We retrospectively analyzed 177 consecutive patients who received these therapies (705 courses in total) at our institute. IFD were observed in 16 courses and the incidence was 2.3 %. A multivariate analysis showed that the factors associated with IFD were primary refractoriness (adjusted odds ratio (aOR), 4.22; 95 % confidence interval (CI), 1.38-13.0; p value = 0.012), two (aOR, 10.5, 95 % CI, 1.20-91.7; p = 0.033) or more (aOR, 26.2; 95 % CI, 3.27-210; p = 0.002) previous treatment lines, and the minimum neutrophil count during the therapies equal to or less than 500/µL (aOR, 9.69; 95 % CI, 1.25-74.9; p = 0.030). Using these factors, we created the IFD scoring model by assigning one point to each of primary refractoriness, two previous treatment lines and treatment that caused neutropenia (≤500/µL minimal neutrophil count) and two points to three or more previous treatment lines. The IFD incidence of lower risk group (IFD score <3) was 0.19 % and that of higher (IFD score ≥3) was 9.0 %. In conclusion, adequate prophylaxis for IFD might be required for patients with primary refractoriness, repeated therapies, or therapies which cause neutropenia. Furthermore, the IFD scoring model of this study underscores the need to account for disease and host factors in determining administration of adequate prophylaxis in salvage treatments for malignant lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fungemia/epidemiología , Linfoma/tratamiento farmacológico , Medición de Riesgo/métodos , Terapia Recuperativa , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Susceptibilidad a Enfermedades , Resistencia a Antineoplásicos , Femenino , Fluconazol/administración & dosificación , Fluconazol/uso terapéutico , Fungemia/etiología , Fungemia/prevención & control , Humanos , Incidencia , Estimación de Kaplan-Meier , Recuento de Leucocitos , Linfoma/complicaciones , Masculino , Persona de Mediana Edad , Neutrófilos , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Although calcineurin inhibitors (CNIs) with short-term methotrexate (stMTX) constitute standard prophylaxis for graft-versus-host diseases (GVHD) in hematopoietic stem cell transplantations (HSCT), comparative efficacy of cyclosporine A (CsA) and tacrolimus (Tac) still remains unclear. We have altered GVHD prophylaxis for standard-risk hematological malignancies from CsA (target trough level, 500 ng/mL) to Tac (15 ng/mL) both with stMTX in May 2008, enabling us to compare the efficacy of CNIs with little selection biases. The cumulative incidence of acute and chronic GVHD was comparable for CsA and Tac. Among the GVHD low-risk patients who received stem cells from matched sibling donors or cord blood, the Tac arm had a trend for favorable control of grade III-IV acute GVHD (6.7 vs. 30.0 %, p = 0.2), which may contribute to the significantly better overall survival (p = 0.048) and relapse-free survival (p = 0.043) in that group. Inadequate concentration of CNIs in early phase of HSCT affected the cumulative incidence of acute GVHD in the CsA but not in the Tac arm. There were no differences in the GVHD incidence and survival outcomes between CsA and Tac in the GVHD high-risk subgroup. This study underlies the significance of maintaining adequate CsA concentration in standard-risk HSCT.
Asunto(s)
Ciclosporina/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/administración & dosificación , Tacrolimus/administración & dosificación , Adolescente , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia/tendencias , Tacrolimus/normas , Resultado del Tratamiento , Adulto JovenRESUMEN
To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo-HCT at our center. Eighty one patients received reduced-intensity conditioning (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although the RIC group was significantly older and included more patients with poor cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between the two groups. In a multivariate analysis, covariates associated with a worse OS were the French-American-British stage of refractory anemia excess blasts in transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20% or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark analyses, we found that the presence of cGVHD significantly improved OS in high-risk patients or the RIC group. However, there was no difference in OS between those with and without cGVHD among low-risk MDS patients. These findings suggest that the graft-versus-leukemia effect may be more beneficial in high-risk patients who do not receive intensive preparative regimens.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/terapia , Adulto , Anciano , Causas de Muerte , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Premedicación , Recurrencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00695-9.
RESUMEN
This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Delirio , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 6 , Humanos , Herpesvirus Humano 6/genética , Calidad de Vida , Estudios Prospectivos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Activación Viral , ADN Viral , CogniciónRESUMEN
Various complications can influence hematopoietic cell transplantation (HCT) outcomes. Renal complications can occur during the early to late phases of HCT along with various factors. However, studies focusing on fatal renal complications (FRCs) are scarce. Herein, we analyzed 36,596 first allogeneic HCT recipients retrospectively. Overall, 782 patients died of FRCs at a median of 108 (range, 0-3,440) days after HCT. The cumulative incidence of FRCs was 1.7% and 2.2% at one and five years, respectively. FRCs were associated with older age, male sex, non-complete remission (non-CR), lower performance status (PS), and HCT comorbidity index (HCT-CI) associated with renal comorbidity in multivariate analysis. The risk factors within 100 days included older age, multiple myeloma, PS, and HCT-CI comorbidities (psychiatric disturbance, hepatic disease, obesity, and renal disease). Older age and male sex were risk factors between 100 days and one year. After one year, HCT-CI was associated with the presence of diabetes and prior solid tumor; total body irradiation was identified as a risk factor. Non-CR was a common risk factor in all three phases. Furthermore, acute and chronic graft-versus-host disease, reactivation of cytomegalovirus, and relapse of underlying disease also affected FRCs. Systematic follow-up may be necessary based on the patients' risk factors and post-HCT events.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Enfermedad Injerto contra Huésped/etiología , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Recurrencia Local de Neoplasia , Factores de Riesgo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
BACKGROUND: As the Japanese population may have less genetic diversity than other ethnic groups, treatment outcomes may be affected when allogeneic hematopoietic cell transplantation is performed in other races. However, evidence explaining the effect of racial differences is limited. METHODS: We used the Japanese National Database to examine the outcomes of first allogeneic bone marrow transplantations (BMTs) performed between Japanese and non-Japanese patients from 1996 to 2021. We performed propensity score matching using sex, age group, underlying disease group, HLA mismatch, conditioning regimen intensity, and BMT implementation age to select Japanese-to-Japanese BMT patients as the controls. RESULTS: The numbers of non-Japanese-to-Japanese and Japanese-to-non-Japanese BMT cases included in the analysis were 48 and 75, respectively, and the following outcomes were compared: overall survival, non-relapse mortality, acute graft-vs-host disease (GVHD) ≥ grade II, chronic GVHD, and engraftment of neutrophils and platelets. Most parameters did not differ when comparing BMTs according to ethnicity; only platelet engraftment was delayed in Japanese-to-non-Japanese BMT but not in non-Japanese-to-Japanese BMT. CONCLUSIONS: The results of this study suggested that BMT performed in Japanese and non-Japanese patients has little effect on treatment outcomes. The results of this study may be useful for donor selection in Japan, where internationalization has progressed in recent years.