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1.
Transplant Cell Ther ; 29(2): 136.e1-136.e7, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36402457

RESUMEN

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.


Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Humanos , SARS-CoV-2 , Médula Ósea , Pueblos del Este de Asia , Pandemias , COVID-19/epidemiología , Sistema de Registros
2.
Leuk Lymphoma ; 63(13): 3092-3099, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36067510

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy characterized by poor prognosis even following an allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 15 patients diagnosed with BPDCN who underwent an allo-HSCT with myeloablative conditioning (MAC) at our center. The male to female ratio was 11:4. The median age of 36 (range: 6-70) years, all patients initially presented with extramedullary lesions (13 with cutaneous lesions, 1 in the breast and 1 in the lymph nodes) and involved the bone marrow, two cases were diagnosed as central nervous system leukemia (CNSL). Nine patients were in CR1 and six patients were in CR2 status prior to HSCT. All patients received the MAC regimen and an unmanipulated graft. All patients successfully engraftment and achieved full donor chimerism. One patient developed poor graft function, three patients developed aGVHD (Grade I, II, and IV), and seven patients developed cGVHD (mild in 6; moderate in 1). The median follow-up time for survival was 34 (range: 6-64) months. The primary endpoint, overall leukemia-free survival (LFS) rate and overall survival rate was 73.3 ± 10.5%. Allo-HSCT with MAC is a valid option for BPDCN patients in complete remission.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante , Enfermedad Aguda , Trastornos Mieloproliferativos/patología , Células Dendríticas/patología
3.
Leuk Lymphoma ; 63(14): 3307-3316, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36067518

RESUMEN

We retrospectively analyzed the outcomes of 240 pediatric SAA patients who underwent unmanipulated alternative HSCT between September 2012 and November 2020 at our center. The incidence of GF (PGF + SGF) was higher in the UCBD cohort compared to the MUD and HID cohorts [(13.5% ± 6.5%) vs (0%), and (1.6% ± 5.3%), respectively, p = .0001]. The incidence of platelet engraftment within 180 days post-HSCT was lower in the UCBD cohort (82.4% ± 2.3%) compared to the HID group (96.2% ± 1.3%) and the MUD group (97.4% ± 0.5%) (p = .020). the median duration time for platelet engraftment in the UCBD cohort was 29 days, longer than in HID cohort 14 days and the MUD cohort 13 days (p = .005). UCBD cohort had a lower 3-year failure-free survival (FFS) (70.5% ± 8.4%) compared to the HID cohort (81.1% ± 4.3%) and the MUD cohort (92.5% ± 3.1%) (p = .030) and lower 3-year GVHD/relapse free survival (GRFS) (63.3% ± 9.5.4%) compared to the HID cohort (75.5% ± 6.8%) and MUD cohort (87.9% ± 4.5%) (p = .002). UCBD-HSCT had inferior FFS and GRFS compared to an HSCT with an HID or MUD in pediatric patients with acquired SAA. A UCBD-HSCT had a higher GF and lower incidence of platelet engraftment and longer platelet engraftment time.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Donante no Emparentado , Estudios Retrospectivos , Donantes de Sangre , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Recurrencia , Acondicionamiento Pretrasplante
4.
Leuk Lymphoma ; 63(5): 1211-1219, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34913818

RESUMEN

We analyzed the outcomes of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH) who underwent either a haploidentical donor (HID) or a matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). Seventeen patients received an HSCT from an HID and 15 patients received an HSCT from an MUD. The median follow-up time of the surviving patients was 36 months (range: 12-96 months). No significant differences were observed in the 3-year overall survival (OS) between the HID and MUD cohorts (74.1%±11.4% vs. 93.3%±6.4%, respectively, p=.222) or in the 3-year failure-free survival (68.8%±11.8% vs. 86.7%±8.8%, respectively, p=.307). Treatment-related mortality occurred in five patients. A univariate analysis of risk factors revealed platelet engraftment failure negatively impacted OS and FFS. We conclude that HID and MUD-HSCT are feasible and can be effective options for those PNH patients with concomitant bone marrow failure, recurrent life-threatening thrombosis, and uncontrollable hemolysis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hemoglobinuria Paroxística , Pancitopenia , Trastornos de Fallo de la Médula Ósea , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/terapia , Humanos , Pancitopenia/etiología , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Donante no Emparentado
5.
Front Immunol ; 13: 1066748, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36685540

RESUMEN

Introduction: We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1). Methods: We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021. Results: The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT. Conclusions: Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia Local de Neoplasia/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Hematológicas/terapia , Enfermedad Crónica
6.
Front Immunol ; 12: 605766, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025637

RESUMEN

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Antígenos CD19 , Antígenos de Neoplasias , Niño , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Pronóstico , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Recurrencia , Retratamiento , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
7.
Hematology ; 26(1): 134-143, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33491597

RESUMEN

Objective: The outcomes of alternative donor hematopoietic stem cell transplantation (HSCT) with unmanipulated grafts for Inherited bone marrow failure syndromes (IBMFS) are discouraging. Our study is to demonstrate that IBMFS with disease-specific characteristics requires a tailored conditioning regimens to enhance engraftment and reduce regimen related toxicities. Methods: We retrospectively analyzed 42 patients diagnosed with IBMFS and transplanted with an alternative donor graft at our center from November 2012 to August 2018. Twenty-seven patients had Fanconi anemia (FA), 7 had dyskeratosis congenita (DC), and 8 had severe congenital neutropenia (SCN). Patients received ex-vivo unmanipulated alternative donor grafts from a matched unrelated donor (MUD) (n = 22), haploidentical donor (HID) (n = 17) and unrelated cord blood donor (UCBD) (n = 3). FA and DC patient subgroups received reduce intensified conditioning (RIC), while SCN patients received a myeloablative conditioning (MAC) regimen. Results: The median follow-up time for the surviving patients was 38 months (range: 9-63 months). The failure-free survival (FFS) for entire cohort was 76.1%, and was 72.4%, 100% and 56.2% for patients with FA, DC and SCN, respectively. There were no primary graft failures. The cumulative incidence of aGVHD at day 100 was 48.1%. The cumulative incidence of cGVHD at 1 and 3 years was 35.0% and 69.3%, respectively. Conclusion: HSCT using alternative donors with unmanipulated grafts and disease-specific conditioning regimens for IBMFS patients shows promising survival.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Donante no Emparentado , Adulto Joven
8.
Ann Hematol ; 100(6): 1579-1591, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33236196

RESUMEN

There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.


Asunto(s)
Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Hermanos , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
9.
Ann Hematol ; 99(12): 2911-2925, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33000361

RESUMEN

Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Donadores Vivos , Hermanos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/tendencias , Prueba de Histocompatibilidad/métodos , Prueba de Histocompatibilidad/tendencias , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/tendencias , Trasplante Haploidéntico/tendencias , Resultado del Tratamiento , Adulto Joven
10.
Ann Hematol ; 99(6): 1389-1400, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32291495

RESUMEN

Two anti-thymocyte globulin (ATG) forms are used in graft-versus-host disease (GVHD) prophylaxis during haploidentical hematopoietic stem cell transplantations (haplo-HSCTs): ATG-thymoglobulin (ATG-T) and ATG-fresenious (ATG-F). However, comparable dosages for haplo-HSCT remain unclear. We compared and evaluated the effects of ATG-T (7.5 mg/kg) or ATG-F (20 mg/kg) dosages in a relatively homogenous population in haplotype HSCT settings. Patients administered ATG-T 7.5 mg/kg (n = 81) or ATG-F 20 mg/kg (n = 35) as part of GVHD prophylaxis during haplo-HSCT were enrolled. Incidence and severity of GVHD, Epstein-Barr virus (EBV) infection, and immune cell recovery were compared using the Mann-Whitney U rank test and chi-square test. Cumulative incidences of GVHD, EBV infection and its subgroups, and relapse mortality were computed; overall survival (OS) was analyzed using the Kaplan-Meier method, with the log-rank test used for univariate comparison. Risk factors for OS were analyzed by the Cox proportional hazards model. Incidence and cumulative incidence of all grades of acute GVHD and subgroups were comparable in both groups (all p > 0.05); however, cumulative incidence of any grade and limited chronic GVHD was significantly higher in the ATG-T group (p = 0.002, p = 0.007, respectively). Cumulative incidences of EBV infections, EBV-DNAemia, and EBV-related diseases were similar; relapse mortality and OS rates were comparable between both groups (all p > 0.05). ATG-T dosage (7.5 mg/kg) appeared comparable to ATG-F dosage (20 mg/kg) for haplo-HSCT. Currently approved ATG-T and ATG-F doses appear efficient to balance the risk-benefit ratio of GVHD, OS, relapse mortality, and EBV infection in haplo-HSCT.


Asunto(s)
Suero Antilinfocítico/administración & dosificación , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/tendencias , Adolescente , Adulto , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Haploidia , Neoplasias Hematológicas/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
11.
Clin Transplant ; 34(6): e13856, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32170765

RESUMEN

Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective alternative to HLA-matched transplantation. However, Epstein-Barr virus (EBV) infection causes morbidity and mortality in patients undergoing haplo-HSCT. Here, we retrospectively evaluated the incidence and risk factors of EBV-DNAemia and EBV-associated diseases in 131 patients who underwent haplo-HSCT. Patients were classified into the no EBV infection groups, EBV-DNAemia group and EBV-associated disease group. Cumulative incidences of acute graft-vs-host disease, EBV infections, overall survival (OS), and relapse were analyzed. The cumulative incidences of EBV-DNAemia and EBV-associated disease were 26.9% and 33.3%, respectively. In multivariate analysis, cytomegalovirus (CMV)-DNAemia was confirmed as an independent risk factor associated with EBV-DNAemia and EBV-associated disease. Patients with EBV-associated disease had higher transplant-related mortality (TRM) rates and lower OS rates, but similar relapse rates. Overall, these findings demonstrated the cumulative incidences of EBV-DNAemia and EBV-associated disease and identified correlations of EBV infection with TRM, relapse, and OS. Additionally, CMV-DNAemia was a risk factor for EBV-DNAemia and EBV-associated disease.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/genética , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo
12.
Virol J ; 16(1): 19, 2019 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-30736814

RESUMEN

BACKGROUND: Haploidentical hematopoietic stem cell transplant (haplo-HSCT) recipients are at high risk for Epstein Barr virus (EBV)-related diseases. EBV-specific CD8+ cytotoxic T cells can control EBV-infected B cell expansion; however, no studies have investigated EBV-specific immune reconstitution after HSCT, particularly haplo-HSCT. Therefore, in this study, we aimed to characterize EBV-specific immune cell reconstitution after haplo-HSCT. METHODS: HLA-A*1101 and HLA-A*0201 pentamers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 19 haplo-HSCT recipients and the results were compared with those in controls. We also compared the EBV-specific pentamer-binding cell frequencies in patients with or without EBV-related diseases by flow cytometry. RESULTS: Pentamer-binding EBV-specific CD8+ T cells were detected at + 30, + 60 and + 90 days after haplo-HSCT in EBV-seropositive patients subjected to haplo-HSCT from an EBV-seropositive donor. The frequencies of the HLA-A*0201/BMLF1-GLC pentamer in haplo-HSCT patients at + 30 days were significantly lower than those in HLA-A*0201-positive healthy controls (p = 0.019) and patients at + 60 days (p = 0.003). The frequencies of the HLA-A*1101/LMP2-SSC pentamer at + 30, + 60, and + 90 days were significantly decreased compared with those in healthy controls (p = 0.009, 0.019, and 0.039, respectively); however, the frequencies of the HLA-A*1101/LMP2-SSC pentamer did not differ significantly among patients at + 30, + 60, and + 90 days (p = 0.886). There was a significant difference in the frequency of the HLA-A*0201/BMLF1-GLC pentamer at + 60 days between patients with and without EBV-related diseases (p = 0.024). Patients with EBV-related diseases showed lower percentages of HLA-A*0201/BMLF1-GLC specific CD8+ T cells. CONCLUSIONS: Haplo-HSCT recipients could generate EBV-specific CD8+ T cells within + 30 days after transplantation. The HLA-A*0201/BMLF1-GLC pentamer cell frequency at + 60 days may be a useful indicator for monitoring EBV-related diseases in patients after haplo-HSCT. Transfusion with EBV-CTLs within 60 days after haplo-HSCT may have prophylactic effects against EBV-related diseases.


Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Antígeno HLA-A11/inmunología , Antígeno HLA-A2/inmunología , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/inmunología , Reconstitución Inmune , Linfocitos T Citotóxicos/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Trasplantes , Adulto Joven
14.
Biol Blood Marrow Transplant ; 24(9): 1881-1887, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29772350

RESUMEN

Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA.


Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anemia Aplásica/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
15.
Pediatr Transplant ; 21(1)2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27885760

RESUMEN

CGD is a rare primary immunodeficiency with high mortality rates when treated conventionally, especially for the X-chromosome-linked form. HSCT is the only curative therapy for CGD; however, haploidentical transplantation in CGD is rare. Here, we report a case of X-linked CGD treated successfully by haploidentical HSCT. The patient showed a positive result with full donor chimerism, good quality of life, and the absence of recurrent infectious diseases at follow-up (68 months). Thus, haploidentical HSCT may serve as an acceptable treatment approach for patients who have CGD, but no HLA-matched related or unrelated donor.


Asunto(s)
Enfermedad Granulomatosa Crónica/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Busulfano/administración & dosificación , Cromosomas Humanos X , Ciclofosfamida/administración & dosificación , Humanos , Masculino , Calidad de Vida , Acondicionamiento Pretrasplante
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 562-7, 2016 Apr.
Artículo en Chino | MEDLINE | ID: mdl-27151030

RESUMEN

OBJECTIVE: To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance. METHODS: A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used. RESULTS: All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%). CONCLUSION: These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.


Asunto(s)
Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Acondicionamiento Pretrasplante , Suero Antilinfocítico/uso terapéutico , Busulfano/uso terapéutico , Ciclosporina/uso terapéutico , Antígenos HLA/genética , Humanos , Incidencia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Trasplante de Células Madre , Donantes de Tejidos , Trasplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
17.
Mol Med Rep ; 12(1): 1059-65, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25815463

RESUMEN

The aim of the present study was to explore the effect of epigenetic modification of class II transactivator (CIITA) methylation on histocompatibility complex (MHC) class II expression and the immune evasion of leukemia HL-60 cells. HL-60 cells were treated with various concentrations of 5-aza-2'deoxycytidine (5-Aza-CdR) and 0.5 µmol/l suberoylanilide hydroxamic acid (SAHA) for 24 h and then stimulated by interferon γ (IFN-γ) for 48 h. The mRNA levels of MHC class I, II and co-stimulatory molecules were quantified by reverse transcription polymerase chain reaction (RT-PCR). The levels of CIITA protein were determined by western blot analysis, and the CpG island methylation ratios in the CIITA promoter IV (CIITApIV) were analyzed by bisulfite-sequencing PCR (BSP). MHC I as well as the co-stimulatory molecules CD40 and CD80 were significantly increased following treatment with 5-Aza-CdR + SAHA + IFN-γ (epigenetic groups) compared with those in the control group and IFN-γ group (P<0.05). The expression of MHC class II and CIITA was restored and increased in an 5-Aza-CdR concentration-dependent manner in the three epigenetic groups. The results of the BSP assay showed that the methylation rate of CIITApIV CpG sites decreased with the treatment of epigenetic modification and negatively correlated to the 5-Aza-CdR concentration. This demonstrated that the negative expression of CIITA protein was the key reason for the loss of MHC II expression in HL-60 cells. The results of the present study may help to illustrate the mechanism of immune evasion in HL-60 cells.


Asunto(s)
Metilación de ADN , Epigénesis Genética/inmunología , Proteínas Nucleares/inmunología , Transactivadores/inmunología , Escape del Tumor/genética , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/análogos & derivados , Azacitidina/farmacología , Antígeno B7-1/genética , Antígeno B7-1/inmunología , Antígenos CD40/genética , Antígenos CD40/inmunología , Islas de CpG , Decitabina , Relación Dosis-Respuesta a Droga , Epigénesis Genética/efectos de los fármacos , Células HL-60 , Humanos , Ácidos Hidroxámicos/farmacología , Interferón gamma/farmacología , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Transactivadores/genética , Escape del Tumor/efectos de los fármacos , Vorinostat
18.
Clin Transpl ; : 245-50, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26281152

RESUMEN

Published reports suggest that engraftment failure after hematopoietic stem cell transplantation (HSCT) is closely associated with the presence of donor-specific HLA antibodies (DSA). Herein, we report a single cohort retrospective analysis of 567 cases of HLA mismatched allogeneic HSCT patients from the Lu Dao-pei Hematology Center, transplanted between September 11, 2012, and November 20, 2014. Of these cases, 306 patients underwent HLA class I and II antibody testing within one month before transplantation. For patients with HLA antibody screening resulting in an HLA antibody with a mean fluorescence intensity (MFI) > 1000, single antigen bead HLA class I and II testing was performed. Then, according to donor HLA genotype, we determined whether DSA were present. Of the 306 patients with pre-transplant HLA antibody screening (LABScreen Mixed Antigen), HLA class I antibodies were present in 51 cases (16.7%). HLA class II antibodies were present in 24 cases (7.8%). Of all antibody positive cases, 20 cases were positive for HLA antibodies on single antigen beads at an MFI > 1000. Half of these cases were DSA positive. Of the non-DSA antibody cases (n = 1 0), there was one case of primary graft failure after HSCT. In the ten DSA positive patients, the HSCT was chosen from the reactive donor. Seven of these cases were treated prior to HSCT with 1-2 times plasmapheresis or high-dose intravenous immunoglobulin (IVIG) therapy. The other three cases had no special treatment to decrease HLA antibodies before transplantation. All 10 DSA positive cases achieved successful engraftment. There was one case of primary graft failure in the group of 273 patients who were HLA antibody negative. Out of the group of 261 patients who did not undergo HLA antibody screening, there were 7 cases of primary engraftment failure. The incidence of engraftment failure was lower in the group of patients who had been screened for HLA antibodies prior to transplant than it was for the patients who had not been screened (2/306 versus 7/261, p = 0.054). Five of the 7 cases of engraftment failure were screened for HLA antibodies at 30 days after first transplantation. The results of five of the cases were negative for HLA antibodies and the patients underwent second transplants, all achieving successful engraftment. This cohort researched HLA antibodies and their effect on engraftment of HSCT in Chinese cases. We compared 306 patients who underwent HLA antibody screening and were given the appropriate treatment before HSCT if DSA were positive, with 261 patients who were not screened for HLA antibodies. We found that the incidence of primary graft failure significantly decreased. Although not directly determined, HLA antibodies (especially DSA) are the cause of engraftment failure and our findings reflect the importance of HLA antibody screening prior to transplantation. We suggest that patients with pre-existing DSA should be treated with plasma exchange or IVIG therapy before transplantation.


Asunto(s)
Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Histocompatibilidad , Isoanticuerpos/sangre , Adolescente , Adulto , Biomarcadores/sangre , China , Desensibilización Inmunológica/métodos , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Plasmaféresis , Valor Predictivo de las Pruebas , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Insuficiencia del Tratamiento , Adulto Joven
19.
Zhonghua Xue Ye Xue Za Zhi ; 33(6): 467-70, 2012 Jun.
Artículo en Chino | MEDLINE | ID: mdl-22967382

RESUMEN

OBJECTIVE: To evaluate the efficacy of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory/recurrent acute myeloid leukemia (AML). METHODS: A total of 45 patients with refractory/recurrent AML were enrolled from September 2006 to April 2010. The median blasts in bone marrow (BM) were 36% (20% to 92%) before conditioning. The donors were identical siblings (6) or unrelated ones (9) or haploidentical family members (30). Conditioning regiments were individualized according to patients' status, the regimen with high-dose cytarabine plus BuCy/CY was mostly used (20). The patients with impaired organ function received above regimen except using fludarabine instead of cyclophosphamide (16). FLAG followed by reduced-intensified BuCy was employed for the recipients with more than 40% blasts in BM (6) to reduce leukemia burden. TBI/CY or TBI/Fludarabine was used for the recipients with extramedullary infiltration of leukemia or multidrug resistant leukemia. G-CSF, MTX, NVT, Vm26, Acla or Thaltipa was added into conditioning regiments according to leukemia character. RESULTS: All but 2 patients attained durable engraftment. The incidence of grade II to IV aGVHD and cGVHD were 34%, 59.1%, respectively. With median follow-up 30 (0.5 - 57) months, the relapse rate was 29.2%. Twenty-nine of 45 (60.2%) patients remained in complete remission since salvaged HSCT. Three-years disease-free survival and overall survival were 60.2% and 62.6%, respectively. CONCLUSION: Our results indicated that the combination of salvaged HSCT with prophylactic immunotherapy might be a promising modality for treatment of refractory/recurrent AML, even with high leukemia burden.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Recurrencia , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(3): 545-8, 2012 Jun.
Artículo en Chino | MEDLINE | ID: mdl-22739152

RESUMEN

This study was purposed to analyze the characteristics of morphology, immunology, cytogenetic and molecular biology of leukemia cells in 12 AML patients with Ph(+) and their correlation with survival of patients. 12 patients with Ph(+) AML were diagnosed according to diagnostic criteria of WHO and existence of t(9;22) (q34;q11) or t(9;22) abnormality, meanwhile no evidence of CML chronic phase was observed. The results showed that 8 out of 12 cases were confirmedly diagnosed to be AML by morphologic and immunophenotypic examination, 4 cases were diagnosed as myeloid and B lymphocytic mixed acute leukemia. The Ph chromosome was detected in 10 cases by chromosome analysis at the first time of diagnosis, and some of the cases had coexistence of complex chromosome and/or normal karyotype. BCR-ABL transcript was detected in all 12 cases, including 7 cases with b3a2, 1 case with b2a2, 1 case with b2a2 variants, 2 cases with e1a2 and 1 case with e18a2. The 12 cases all got complete remission after chemotherapy and/or gleevec treatment, out of them 3 cases received chemotherapy and gleevec treatment, but 2 cases died; 9 cases received allogeneic hematopoietic stem-cell transplantation (allo-HSCT), 1 case died from relapse, among them 1 case died from transplant complications. The median survival was 24 (8 - 80) months, the overall survival of 3 years was (51.4 ± 17.7)%. It is concluded that the Ph(+) AML is a acute myelogenous leukemia with poor prognosis, but long-term survival may be achieved with HSCT as quick as after complete remission from gleevec and chemotherapy treatment. Meanwhile, the detection of BCR-ABL gene and it variants may be give more opportunity for diagnose and treatment, which can be used as routine screening for newly diagnosed leukemia.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Niño , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pronóstico
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