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BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).
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Accidente Cerebrovascular Isquémico , Imagen por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Trasplante Autólogo/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Resultado del Tratamiento , Adulto , Estudios de FactibilidadRESUMEN
BACKGROUND: Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers. METHODS: The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells. RESULTS: Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation. CONCLUSIONS: A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).
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Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Humanos , Filgrastim/efectos adversos , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Polietilenglicoles/efectos adversos , Antígenos CD34/metabolismo , Proteínas Recombinantes/efectos adversosRESUMEN
Background: Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. Poor prognosis has been shown in patients with cGVHD after the failure of primary steroid-based treatments. A previous report demonstrated the efficacy and safety of ibrutinib in these patients, leading to the approval of ibrutinib for cGVHD in Japan. Here, we report the extended follow-up of patients in this study. Objectives: To evaluate the safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD. Study Design: An open-label, single-arm, multicenter study of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD (NCT No.: NCT03474679; Clinical Registry No.: CR108443). Results: At the time of the final data cutoff, 7/19 (36.8%) patients completed the study treatment, and 12/19 (63.2%) patients discontinued ibrutinib. After a median follow-up of 31.11 months (range:1.9 to 38.6 months), the best overall response rate was 84.2% (16/19 patients; 95% CI:60.4%, 96.6%) in all treated populations, with a median time to response of 2.81 (range:1.0 to 27.6) months. Of 15 responders with ≥2 organs involved at baseline, seven (46.7%) had responses in multiple organs. An improvement in the organ response rate was observed for the skin, eye, mouth, and esophagus compared with that in a previous report. The rate of sustained response for ≥20 weeks, ≥32 weeks, and ≥44 weeks were 68.8%, 62.5%, and 50.0%, respectively for 16 responders. The median daily corticosteroid dose requirement tended to decrease over time for all treated analysis sets. Twelve of 19 patients (63.2%) reached a corticosteroid dose of <0.15 mg/kg/day for at least one week, and four (21.1%) discontinued corticosteroid treatment for at least 28 days during the study. The failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively. The safety findings of this updated analysis were consistent with the safety profile observed at the time of the primary analysis and the known ibrutinib safety profile. Common grade ≥3 treatment-emergent adverse events (TEAEs) were pneumonia (6/19 [31.6%] patients), platelet count decreased, and cellulitis (3/19 [15.8%] patients each). After the primary analysis, no new TEAEs leading to death, treatment discontinuation, or dose reduction were reported, and no new patients reported major hemorrhage. Cardiac arrhythmia (Grade 2 atrial flutter) was reported in 1/19 (5.3%) patients. No new safety signs were observed despite prolonged ibrutinib exposure. Conclusions: The final results support previous conclusions, demonstrating a clinically meaningful response and acceptable safety profile of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.
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Hepatic sinusoidal obstruction syndrome (SOS) is a severe and life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a multi-center retrospective study to evaluate the utility of our ultrasonographic scoring system for the diagnosis of SOS (HokUS-10) in predicting SOS-related mortality (SOS-RM). We analyzed a total of 42 patients who developed SOS after HSCT. The cumulative incidences of SOS-RM, non-relapse mortality (NRM), and overall survival at day 180 after the diagnosis of SOS were 26.4%, 28.8% and 54.5%, respectively. The area under the receiver operating characteristic curve analysis showed that the optimal cut-off value of HokUS-10 total score to predict SOS-RM was 8 points after the treatment of SOS. In the individual HokUS-10 score, ascites and portal vein flow-related scores (PV mean velocity and PV flow direction) after the treatment of SOS were shown as significant risk factors for SOS-RM. Our study suggested that US findings after the treatment can predict the treatment outcomes for SOS.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Humanos , Enfermedad Veno-Oclusiva Hepática/diagnóstico por imagen , Enfermedad Veno-Oclusiva Hepática/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Trasplante de Células Madre Hematopoyéticas/efectos adversosAsunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Adulto , Humanos , Herpesvirus Humano 4 , Viremia/etiología , Incidencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/complicacionesRESUMEN
The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.
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Background: α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients. Methods: Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019. Results: Noninfectious IP was observed in 694 patients at a median (range) of 63 (0-1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0-903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48-4.25), along with total body irradiation (>8â Gy; HR, 1.57; 95% CI, 1.18-2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004-1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45-0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49-0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001). Conclusions: Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.
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We retrospectively compared outcomes of unrelated donor bone marrow transplant (UBMT) and HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) using the Japanese registry data. Recipients of first HCT for acute leukemia and myelodysplastic syndromes between 2012 and 2015 were included. The analyzed subjects comprised UBMT recipients with 8/8 matched HLA alleles (n = 1470), 7/8 matched alleles (n = 859), 6/8 matched alleles (n = 186), and recipients of PTCy-haploPBSCT (n = 133). In multivariate analyses with 8/8 matched UBMT as the reference, PTCy-haploPBSCT showed similar overall mortality, decreased risk of non-relapse mortality (NRM), increased risk of relapse, and decreased risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD. Adjusted probabilities for 8/8 matched UBMT, PTCy-haploPBSCT, and 7/8 and 6/8 matched UBMT groups at 2 years post-transplant were 61%, 60%, 58%, and 52% for overall survival, 23%, 28%, 21%, and 19% for relapse, and 20%, 7%, 24%, and 33% for NRM. PTCy-haploPBSCT was associated with remarkably low NRM, contributing to survival outcomes that were comparable to 8/8 matched UBMT. The higher relapse rate in the PTCy-haploPBSCT group might be associated with the higher proportion of high-risk patients. PTCy-haploPBSCT may be a viable alternative when HLA-matched related donors are not available.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Trasplante de Médula Ósea , Estudios Retrospectivos , Donante no Emparentado , Ciclofosfamida/uso terapéutico , Leucemia Mieloide Aguda/terapia , RecurrenciaRESUMEN
Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por Virus de Epstein-Barr , Infecciones por VIH , Tumor de Músculo Liso , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Herpesvirus Humano 4 , Humanos , Masculino , Tumor de Músculo Liso/tratamiento farmacológico , Tumor de Músculo Liso/patologíaRESUMEN
HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) and umbilical cord blood transplantation (UCBT) are alternative to HLA-matched stem cell transplantation. We conducted a matched-pair analysis of PTCy-haplo and UCBT using the Japanese registry data. We identified 136 patients aged between 16 and 69 years who received PTCy-haplo as their first transplantation for acute leukemia or myelodysplastic syndromes. Control group included 408 UCBT recipients selected to match the PTCy-haplo group. Overall and relapse-free survival probabilities at 2 years were comparable between the PTCy-haplo and UCBT groups: 55% vs. 53% for overall survival (p = 0.46), and 47% vs. 48% for relapse-free survival (p = 0.79), respectively. The cumulative incidence of relapse was significantly higher (43% vs. 29%, respectively, p = 0.006), while the cumulative incidence of non-relapse mortality (NRM) was significantly lower (9% vs. 23%, respectively, p < 0.001) in the PTCy-haplo group. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was lower in the PTCy-haplo group compared to the UCBT group (29% vs. 41%, respectively, p = 0.016), while those of grade III-IV acute GVHD and chronic GVHD were not statistically different between the two groups. Our results suggest that both PTCy-haplo and UCBT are viable alternatives to HLA-matched stem cell transplantation.
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Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Ciclofosfamida/uso terapéutico , Leucemia Mieloide Aguda/complicaciones , Recurrencia , Acondicionamiento Pretrasplante/métodos , Estudios RetrospectivosAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Albúminas , Creatinina , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Estudios Retrospectivos , Trasplante Homólogo/efectos adversosRESUMEN
Antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis has been demonstrated for chronic GVHD inhibition by a series of randomized control trials. The optimal dose of ATG remained unestablished; however, the recommended dose of ATG by the European Group for Blood and Marrow Transplantation has recently decreased. While a lower ATG dose has been used in Japan, ATG usage is recommended in peripheral blood stem cell transplantation or human leukocyte antigens (HLA) 1-locus mismatched bone marrow transplantation with myeloablative conditioning from the nation-wide retrospective studies showing that ATG inhibited chronic GVHD and improved GVHD-free, relapse-free survival. The association of absolute lymphocyte counts (ALC) before ATG administration with transplant outcomes has been reported, which suggests a possible strategy to individualize the ATG dose according to ALC before ATG. Recent studies compared the transplant outcomes using ATG and post-transplant cyclophosphamide, which has rapidly spread in haploidentical transplantation; however, further studies are needed to establish those positioning in HLA-matched/mismatched transplantation.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Suero Antilinfocítico/uso terapéutico , Humanos , Estudios Retrospectivos , Acondicionamiento PretrasplanteRESUMEN
A 57-year-old man visited the urology department with a painful mass on the dorsal side of the penis. Magnetic resonance imaging sagittal image showed a small nodule. Leukemia recurrence was suspected due to his history of treatment for acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation. No recurrence was identified by bone marrow biopsy ; however, two months later, the recurrence of leukemia was strongly suspected because the tumor grew over time and blasts were found in the peripheral blood. A biopsy of the penile tumor and bone marrow was performed, leading to the diagnosis of granulocytic sarcoma. Patients with a history of leukemia may be preceded by a single recurrence to extramedullary organs, even if blood and bone marrow findings suggest remission.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Pene/diagnóstico por imagen , Pene/patología , Pene/cirugía , Recurrencia , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/cirugíaRESUMEN
Although haploidentical donor lymphocyte infusion (DLI) is a valid treatment option for relapsed acute myeloid leukemia (AML), the incidence and risk factors for graft-versus-host disease (GVHD) and the efficacy of haploidentical DLI have not been fully evaluated. We retrospectively analyzed the outcomes after haploidentical DLI for 84 patients with AML using a nationwide database and additional questionnaires. The median number of DLI cycles and infused CD3+ cell dose was 1 and 1.0 × 106/kg, respectively. The infused CD3+ cell count of 5.0 × 105/kg or higher was associated with acute GVHD (grade II-IV, 32.1% vs. 10.5%, p = 0.03; grade III-IV, 21.4% vs. 5.3%, p = 0.10). Patients who developed grade III-IV acute GVHD more frequently succumbed to treatment-related mortality (46.7% vs. 15.8% at 1 year, p = 0.002), although the relapse-related mortality was significantly low (40.0% vs. 72.2% at 1 year, p = 0.025). The overall response to DLI was significantly higher in the preemptive DLI group (47.4%) than in the therapeutic group (13.9%, p = 0.002). In the multivariate analysis, preemptive DLI was the predictive factor for overall response (odds ratio, 5.58; p = 0.003). Our results indicated the substantial risk of acute GVHD after haploidentical DLI with CD3+ cell count of 5.0×105/kg or higher and the favorable outcomes after preemptive DLI.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Transfusión de Linfocitos , Adolescente , Adulto , Donantes de Sangre , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
We retrospectively compared the outcomes of reduced-intensity conditioning (RIC) transplantation from matched related donors (MRD; n = 266), matched unrelated donors (MUD; n = 277), and umbilical cord blood (UCB; n = 513) for mature lymphoid malignancies. The 3-year overall survival rates for the MRD, MUD, and UCB groups were 54%, 59%, and 40%, respectively (P < 0.001). Multivariate analysis showed no differences in survival between the MRD group and the MUD or UCB group. However, survival was significantly affected by the conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in the UCB group, but not in the MRD and MUD groups. Notably, multivariate analysis showed that the risk of overall mortality in the UCB recipients who received the optimal conditioning regimen and GVHD prophylaxis (n = 116) was lower than that in the MRD group (relative risk [RR], 0.69; P = 0.03) and tended to be lower than that in the MUD group (RR, 0.75; P = 0.09). Our results suggest that UCB transplantation performed with the optimal conditioning regimen and GVHD prophylaxis is highly effective. Moreover, UCB is readily available. Thus, UCB transplantation with the optimal conditioning regimen and GVHD prophylaxis is preferable to MUD transplantation when MRD are not available in the setting of RIC transplantation for mature lymphoid malignancies.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Humanos , Estudios Retrospectivos , Trasplante de Células Madre , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Donante no EmparentadoRESUMEN
Previous Japanese studies have shown that bone marrow transplantation (BMT) is associated with better survival compared with peripheral blood stem cell transplantation (PBSCT) from a matched related donor (MRD). PBSCT recipients have shown higher incidences of severe graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) compared with BMT recipients. In recent years, the efficacy and safety of antithymocyte globulin (ATG) for PBSCT recipients has been evaluated worldwide. In the present study, we aimed to compare BMT and PBSCT recipients to identify current improvements and unmet needs among MRD PBSCT recipients. In addition, we evaluated the impact of ATG administration on the outcomes of PBSCT recipients. We retrospectively analyzed patients age ≥16 years with acute leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia who underwent their first BMT or PBSCT from an MRD between 2009 and 2018 in Japan. A total of 3599 transplantations were performed (BMT, n = 1218; PBSCT without ATG [PBSCT-ATG(-)], n = 2288; PBSCT with ATG [PBSCT-ATG(+)], n = 93). The PBSCT-ATG(-) group had a higher NRM (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.08 to 1.57; P = .005) and lower overall survival (OS) (HR, 1.16; 95% CI, 1.04 to 1.30; P = .011) compared with the BMT group. Furthermore, the PBSCT-ATG(-) group had higher incidences of grade III-IV, stage 2-4 gut, high-risk, and steroid-refractory acute GVHD compared with the BMT group. Acute GVHD had a negative impact on NRM and OS. The PBSCT-ATG(-) group also was associated with an elevated risk of chronic GVHD (HR, 1.89; 95% CI, 1.24 to 2.57; P < .001) and extensive chronic GVHD (HR, 1.44; 95% CI, 1.23 to 1.68; P < .001). The incidences of acute GVHD, chronic GVHD, and NRM and chronic GVHD-free relapse-free survival rates were comparable between the PBSCT-ATG(+) and BMT groups. The OS of patients with acute GVHD was similar in the 3 donor groups. Patients treated with reduced-intensity conditioning in the PBSCT-ATG(+) group had a higher relapse rate and lower OS rate compared with those in the BMT group. In this Japanese cohort, standard calcineurin inhibitor-based GVHD prophylaxis was not sufficient for recipients of MRD PBSCT because of the high incidence of severe acute GVHD. Prophylactic ATG was found to be a promising strategy against GVHD.
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Enfermedad Injerto contra Huésped , Leucemia Mieloide Aguda , Trasplante de Células Madre de Sangre Periférica , Adolescente , Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mieloide Aguda/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Recurrencia , Estudios RetrospectivosRESUMEN
Relapsed acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with poor prognosis. In a subset of patients, durable remissions can be achieved with a second allo-HSCT (allo-HSCT2). However, many patients experience relapse after allo-HSCT2 and they may be considered for a third allo-HSCT (allo-HSCT3). Nevertheless, the benefit of allo-HSCT3 remains unconfirmed. Thus, herein a retrospective analysis of 253 allo-HSCT3s in patients with relapsed/refractory acute leukemia was carried out. In total, 29 (11.5%) survived at a median follow-up of 794 days (range: 87-4 619). The 3-year leukemia-free survival and overall survival (OS) rates were 9.7% and 10.9%, respectively. Patients who maintained remission for ≥2 years after allo-HSCT2 had a significantly better 3-year OS (35.8%) than those who experienced early relapse (<1 year, 7.8%; 1-2 years, 14.0%; P = 0.004). Complete remission at allo-HSCT3, performance status score of 0-1 at allo-HSCT3, grade I acute graft-versus-host disease after allo-HSCT2, and relapse ≥2 years after allo-HSCT2 were associated with better survival in patients who received allo-HSCT3. The prognosis after allo-HSCT3 in patients with relapsed/refractory acute leukemia is generally unfavorable. However, given the lack of alternative treatment options, allo-HSCT3 may be considered in a group of patients.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Enfermedad Aguda , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mieloide Aguda/terapia , Recurrencia , Estudios RetrospectivosRESUMEN
Antithymocyte globulin (ATG) decreases chronic graft-versus-host disease (cGVHD) in peripheral blood stem cell transplantation (PBSCT); however, the optimal ATG dose has not been elucidated. We conducted a matched-pair analysis to evaluate whether low-dose ATG could inhibit cGVHD in HLA-matched PBSCT after myeloablative conditioning. A total of 70 patients who were enrolled in the JSCT-ATG15 study, a multicenter phase II clinical trial of 2 mg/kg of ATG (thymoglobulin) given on days -2 and -1, were compared with 210 patients not receiving ATG, who were matched for age, sex, disease, and calcineurin inhibitor selected from the database in Japan. The primary endpoint, cumulative incidence of extensive cGVHD at 2 years was significantly less in the ATG group than that in the non-ATG group (8.7% [95% CI, 3.5%-16.8%] versus 26.2% [95% CI, 20.3%-32.5%], P = .002). ATG significantly reduced the incidence of overall cGVHD and inhibited multiple organ involvement. The ATG group had favorable outcome compared to the non-ATG group in GVHD-free, and relapse-free survival at 2 years. In conclusion, low-dose ATG effectively inhibits chronic GVHD in PBSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Análisis por Apareamiento , Trasplante de Células Madre de Sangre Periférica/efectos adversosRESUMEN
Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years. Treatment outcomes were compared with those of 1792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% vs 29%, respectively; P < .001), with a much higher proportion of patients receiving allo-HCT (80% vs 34%, respectively; P < .001) and a shorter interval from diagnosis to allo-HCT (median, 128 vs 170 days, respectively; P < .001). Among the 90 patients who received allo-HCT (cord blood, n = 30; HLA-haploidentical related donors, n = 20; other related donors, n = 14; other unrelated donors, n = 26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered at the UMIN Clinical Trials Registry as #000017672.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma de Células T del Adulto , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Donante no EmparentadoRESUMEN
There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.