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1.
Br J Haematol ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741461

RESUMO

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

2.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229053

RESUMO

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumonia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
4.
Front Med (Lausanne) ; 8: 604085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150785

RESUMO

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days-6 to-2) and cyclophosphamide (1,000 mg/m2/day) (days-5 to-4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8-55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35-120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95-12.51) × 108/kg and CD34 + cells 2.28 (0.75-5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10-20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

5.
Leukemia ; 35(11): 3092-3100, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33824464

RESUMO

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.

6.
BMC Cancer ; 21(1): 292, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740924

RESUMO

BACKGROUND: Sequential monitoring of Wilms' tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. METHODS: Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan-Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. RESULTS: Of the 151 consecutive patients included, the median age was 10 years (range, 1-17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25-6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. CONCLUSIONS: Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/epidemiologia , Proteínas WT1/metabolismo , Adolescente , Biomarcadores Tumorais/análise , Medula Óssea/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Prognóstico , Medição de Risco/métodos , Transplante Homólogo , Proteínas WT1/análise
7.
Ann Hematol ; 100(5): 1267-1281, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33712867

RESUMO

The prognosis of 11q23/KMT2A-rearranged (KMT2A-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important prognostic factor for relapse. Thus, we aimed to identify the evolution of KMT2A before and after allo-HSCT and the efficacy of preemptive immunotherapies for KMT2A-r AL patients receiving allo-HSCT. KMT2A expression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutive KMT2A-r AL patients. Pre-HSCT KMT2A positivity was correlated with post-HSCT KMT2A positivity (correlation coefficient=0.371, P<0.001). The rates of achieving KMT2A negativity after allo-HSCT were 96.6%, 92.9%, and 68.8% in the pre-HSCT low-level group (>0, <0.1%), intermediate-level group (≥ 0.1%, <1%), and high-level group (≥1%), respectively. The rates of regaining KMT2A positivity after allo-HSCT were 7.7%, 35.7%, 38.5%, and 45.5% for the pre-HSCT KMT2A-negative, low-level, intermediate-level, and high-level groups, respectively (P<0.001). The 4-year cumulative incidence of relapse after allo-HSCT was as high as 53.7% in the pre-HSCT KMT2A expression ≥ 0.1% group, which was compared to the KMT2A-negative group (15.1%) and KMT2A <0.1% group (31.2%). The clinical outcomes of patients with post-HSCT KMT2A positivity were poorer than those of patients with persistent KMT2A negativity. Although post-HSCT preemptive immunotherapies might help to achieve KMT2A negativity, the long-term efficacy was unsatisfactory. Thus, pre-HSCT KMT2A positivity was significantly associated with post-HSCT KMT2A positivity. The clinical outcomes of patients with post-HSCT KMT2A positivity were poor, which might not be overcome by commonly used immunotherapies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/diagnóstico , Proteína de Leucina Linfoide-Mieloide/genética , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Rearranjo Gênico , Humanos , Imunoterapia , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Neoplasia Residual/terapia , Prognóstico , Transplante Homólogo , Adulto Jovem
8.
Transpl Infect Dis ; 23(3): e13544, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33326670

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation is relatively common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the incidence of HHV-6 reactivation and the clinical outcomes following unmanipulated haploidentical HSCT (haplo-HSCT) remain unknown. METHOD: We prospectively monitored blood HHV-6 DNA using real-time quantitative polymerase chain reaction weekly until day 100 post unmanipulated haplo-HSCT in patients with hematological malignancies. RESULTS: From November 2016 to March 2017, 102 patients (58 male and 44 female, median age 25(2-58) years old) were enrolled. Within 100 days post-transplantation, 27 patients (27/136, 19.9%) developed HHV-6 viremia with a median onset time of 14 (7-98) days. The cumulative incidence of HHV-6 reactivation on day 100 post-HSCT was 25.5 ± 4.3% in haplo-HSCT. The median HHV-6 copy number was 1.45 × 103 (5.48 × 102 -2.00 × 104 ) copies/ml. The HHV-6 viremia duration time was 7 days in 23 patients, 14 days in one patient and 21 days in one patient. In multivariate analysis, prior HHV-6 reactivation was an independent risk factor for grade 2-4 graft-versus-host disease (GVHD). But it did not influence the overall survival (OS)(HR 1.624, 95%CI 0.768-3.432, P = .204), disease-free survival (DFS) (HR 1.640, 95%CI 0.799-3.367, P = .177) and non-relapse mortality (NRM) (HR 1.644, 95%CI 0.670-4.038, P = .278). CONCLUSION: The reactivation of HHV-6 after unmanipulated haploidentical transplantation predicts the occurrence of grade 2-4 a-GVHD, but it may not influence the overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM).


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Infecções por Roseolovirus , Ativação Viral , Adulto Jovem
9.
Clin Transplant ; 35(2): e14160, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33222318

RESUMO

OBJECTIVES: The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS: A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS: Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. CONCLUSIONS: Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Quimerismo , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Fatores de Proteção , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento
10.
Clin Lymphoma Myeloma Leuk ; 21(2): e126-e136, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33060049

RESUMO

BACKGROUND: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for children with intermediate-risk acute myeloid leukemia (IR-AML) in first complete remission has been controversial. The present study compared the effect of chemotherapy with unmanipulated haplo-HSCT as treatment of patients with IR-AML in first complete remission (CR1). PATIENTS AND METHODS: We retrospectively analyzed the outcomes of 80 children with IR-AML and compared the effects of chemotherapy (n = 47) with those of haplo-HSCT (n = 33) as treatment in CR1. RESULTS: The 3-year overall survival, event-free survival (EFS), and cumulative incidence of relapse (CIR) was 85.4% ± 4.1%, 73.2% ± 5.0%, and 25.4% ± 4.5%, respectively. Compared with the chemotherapy group, the patients in the haplo-HSCT group had a lower CIR (P = .059) and better EFS (P = .108), but roughly equivalent overall survival (P = .841). Multivariate analysis revealed chemotherapy and minimal residual disease (MRD) of ≥ 10-3 after induction therapy as independent risk factors affecting CIR and EFS. EFS (P = .045) and CIR (P = .045) differed significantly between the 2 treatment groups in patients with MRD of ≥ 10-3 after induction therapy. CONCLUSION: Haplo-HSCT might be a feasible option for children with IR-AML in CR1, especially for patients with MRD of ≥ 10-3 after induction therapy.

11.
Front Immunol ; 12: 731435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069522

RESUMO

Background: The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear. Methods: We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission. Results: A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8-90.7%) vs. 68.7% (95% CI, 47.7-89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8-90.7%) vs. 28.6% (95% CI, 4.9-52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion. Conclusions: Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.


Assuntos
Transferência Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida
12.
Cytotherapy ; 22(12): 755-761, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32861622

RESUMO

BACKGROUND AIMS: The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive. METHODS: The authors focused on the survival of 35 patients with B-cell acute lymphoblastic leukemia who relapsed after allo-HSCT and received CAR T cells. RESULTS: Of the 34 eligible patients, 30 achieved minimal residual disease-negative complete remission (CR), with a total CR rate of 85.7% (79.8-91.6%). There were 14 patients who received various forms of additional therapy after achieving CR. After a median follow-up of 20.7 months, it was noted that 17 patients had relapsed at a median of 4.5 months (2-34 months). The cumulative recurrence rate (RR) at 18 months was 68.3% (57.6-79.0%). Additional treatment did not reduce the RR but seemed to delay the time to relapse (mean: 5.9 months vs 13.1 months; P = 0.046). Patients with a lower tumor burden (≤10%) had a lower RR (25.0% vs 78.6% at 12 months; P = 0.006). The overall survival (OS) rate for the CR patients was 30.0% (20.3-29.7%) at 18 months, with a median OS of 12.7 months. CONCLUSIONS: The authors' study indicated that for patients who relapsed after HSCT, although a high CR rate was achieved after CAR T therapy, the long-term efficacy was unsatisfactory. It is necessary to optimize additional treatment, including a second HSCT, to further improve long-term efficacy after CAR T infusion.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Adulto , Linfócitos B/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interleucina-2/metabolismo , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/metabolismo , Recidiva , Indução de Remissão , Linfócitos T/imunologia
13.
Pediatr Transplant ; 24(7): e13793, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32741088

RESUMO

The specific description, risk factors, and outcomes of aGVHD in pediatric haplo-HSCT using TCR protocols without PT-Cy have not been well described previously. We evaluated the incidence, risk factors, and outcomes of aGVHD in 350 consecutive pediatric patients receiving TCR haplo-HSCT without PT-Cy according to the Glucksberg and NIH aGVHD classifications between January 2015 and December 2017 at Peking University Institute of Hematology. The cumulative incidences of grade I, II, III, and IV aGVHD were 28%, 29.7%, 8.3%, and 5.1%, respectively. The type of aGVHD onset was classic in 243 patients (97.2%), and persistent/recurrent/late-onset aGVHD was in seven patients (2.8%). None of the considered variables significantly influenced the incidence of grade III-IV aGVHD. The 3-year OS, DFS, cumulative incidence of NRM, and relapse in malignant disease between severe aGVHD (III-IV) group and grade 0-II aGVHD group were 61.5% vs 77.2% (P = .027), 58.6% vs 75.1% (P = .014), 19.8% vs 5.3% (P = .002), and 21.6% vs 19.6% (P = .59), respectively; in non-malignant diseases, the 3-year OS, DFS, and NRM were 81.8% vs 97.4% (P = .05), 81.8% vs 97.4% (P = .05), and 18.2% vs 2.6% (P = .05), respectively. Under the protocol of pediatric TCR haplo-HSCT without PT-Cy, the persistent/recurrent/late-onset aGVHD was rare, and the incidence of severe aGVHD was acceptable and significantly contributed to NRM and lower survival in both malignant disease and non-malignant diseases.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunidade Celular , Linfócitos T/microbiologia , Adolescente , Adulto , Biópsia , Criança , China/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Condicionamento Pré-Transplante , Adulto Jovem
14.
Biol Blood Marrow Transplant ; 26(9): 1655-1662, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32504861

RESUMO

The specific description, risk factors, and outcomes of chronic graft-versus-host disease (cGVHD) in pediatric patients with hematologic malignancies after T cell-replete (TCR) myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with antithymocyte globulin (ATG)/granulocyte colony-stimulating factor (G-CSF) have not been previously well described. We retrospectively analyzed the incidence, risk factors, and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria (NIH-CC) in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF between January 2015 and December 2017. A total of 170 patients experienced cGVHD. The 3-year cumulative incidence of total cGVHD and mild, moderate, and severe cGVHD was 57.9%, 27.5%, 18.8%, and 11.9%, respectively. Multivariate analysis showed that acute GVHD (aGVHD) grade II-IV (hazard ratio, 1.578; P = .002) was an independent risk factor for cGVHD. Compared to patients without cGVHD, patients with cGVHD demonstrated a lower 3-year relapse (17.6% versus 27.2%; P = .009), a similar 3-year nonrelapse mortality (NRM) (5.9% versus 5.4%; P = .79), and better 3-year disease-free survival (DFS) (77.8% versus 66.9%; P = .007) and overall survival (OS) (81.3% versus 68.6%; P = .001), particularly those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on relapse, NRM, DFS, or OS was seen. In conclusion, the incidence of severe cGVHD in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF was acceptable. Previous aGVHD grade II-IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse, translating into improved DFS and OS in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Soro Antilinfocitário , Criança , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Linfócitos T , Condicionamento Pré-Transplante
15.
BMC Cancer ; 20(1): 553, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539815

RESUMO

BACKGROUND: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. METHODS: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed. RESULTS: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009). CONCLUSIONS: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/epidemiologia , Proteínas de Fusão Oncogênica/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Quimioterapia de Consolidação/métodos , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Proteínas Proto-Oncogênicas c-kit/genética , Transplante Homólogo/métodos
16.
Cancer Commun (Lond) ; 40(2-3): 93-104, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32175698

RESUMO

BACKGROUND: Human leukocyte antigen-identical sibling donor (ISD)-hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high-risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML. However, the role of HID-SCT in high-risk pediatric AML is unclear. METHODS: To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT, we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT (n = 23) or HID-SCT (n = 156). Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. RESULTS: The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD-SCT group and the HID-SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II-IV acute graft-versus-host disease (GVHD) were 13.0% in the ISD-SCT group and 34.8% in the HID-SCT group (P = 0.062), with a three-year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group (39.1% vs. 16.4%, P = 0.027); with non-relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three-year overall survival rates were 73.0% for the ISD-SCT group and 74.6% for the HID-SCT group (P = 0.689). In subgroup analysis, the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group (50.0% vs. 9.2%, P = 0.001) and the three-year DFS in the ISD-SCT group (50.0%) was lower than that in the HID-SCT group (81.2%) (P = 0.021). CONCLUSIONS: Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico , Adolescente , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Leucemia Mieloide Aguda/mortalidade , Masculino , Recidiva , Irmãos
17.
Leuk Res ; 91: 106333, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32109757

RESUMO

B-cell acute lymphoblastic leukemia (B-ALL) with MLL-rearrangements (MLL-r) is rare in pediatric patients (aged >1 year), and optimal treatment strategies remain unclear. This study aimed to retrospectively evaluate the clinical characteristics, outcomes, and effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) of 37 non-infant children with t(v;11q23)/MLL-r B-ALL. Their 4-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 69.8 %, 58.2 %, and 39.1 %, respectively, and differed significantly between patients receiving allo-HSCT (18/19 cases received haploidentical [haplo]-HSCT) at the first complete remission (HSCT at CR1, n = 19; 87.4 %, 89.5 % and 5.3 %) and those continuing consolidation therapy (Non-HSCT at CR1, n = 18; 52.2 %, 25.9 %, and 74.1 %, respectively), and the p values were 0.022, <0.001 and <0.001, respectively. Of the 13 patients experiencing relapse during consolidation chemotherapy, the five continuing with chemotherapy only died within 44 months, and the eight patients opting for allo-HSCT after CR2 had a 4-year OS of 57.1 %. Multivariate analysis revealed HSCT at CR1 as the only independent protective factor for OS, EFS, and CIR. The present results indicate that allo-HSCT (especially haplo-HSCT) at CR1 may decrease the relapse rate and improve the prognosis of non-infant children with t(v;11q23)/MLL-r B-ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Asparaginase/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Daunorrubicina/uso terapêutico , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Haplótipos , Humanos , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Translocação Genética , Transplante Haploidêntico , Vincristina/uso terapêutico
18.
Bone Marrow Transplant ; 55(6): 1147-1160, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31992849

RESUMO

This study investigated the epidemiological characteristics of cytomegalovirus retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (HSCT). We studied a cohort of 1466 consecutive patients who had undergone haploidentical HSCT between 2013 and 2017. We documented 34 episodes of CMVR in 31 patients, with a median onset of 167 days after the transplant. The cumulative incidence of CMVR was 2.3% 1 year after the transplant. Multivariate analysis suggested that platelet engraft failure at 100 days, EBV DNAemia, refractory or recurrent CMV DNAemia, and acute graft-versus-host disease were related to the development of CMVR in patients with CMV DNAemia. Patients with ≥3 risk factors (high risk) had a higher 1-year incidence of CMVR than patients with ≤2 risk factors (low risk) (26.2% vs. 0.6%, P < 0.001). In patients with CMVR, visual acuity (VA) improved in 16 episodes, remained stable in 10 episodes, and worsened in 8 episodes. The variable related to the improvement of VA was VA ≥ 0.1 at time of CMVR diagnosis. Our study showed that CMVR was a rare complication after haploidentical HSCT but that the risk was greater in patients with multiple risk factors.


Assuntos
Retinite por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Retinite por Citomegalovirus/epidemiologia , Retinite por Citomegalovirus/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco
19.
Bone Marrow Transplant ; 55(6): 1068-1075, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31932654

RESUMO

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Sistema ABO de Grupos Sanguíneos , Anemia Aplástica/terapia , Incompatibilidade de Grupos Sanguíneos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
20.
Biol Blood Marrow Transplant ; 26(2): 351-357, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704470

RESUMO

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplant (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2 to 9). The day 28 overall response rate was 85%, with complete response in 74% of patients, partial response in 11% of patients, and no response in 15% of patients. The day 28 overall response rates were 94.6% in skin SR aGVHD, 81.6% in gut SR aGVHD, and 66.7% in liver SR aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), cytomegalovirus viremia (53%), Epstein-Barr virus viremia (11%), human herpesvirus-6 viremia (7%), and herpes simplex virus viremia (1%). The 3-year overall survival, disease-free survival, nonrelapse mortality, and relapse rates between responders and nonresponders were 81.3% versus 46.7% (P < .001), 79.0% versus 46.7% (P = .001), 6.1% versus 33.3% (P < .001), and 14.9% versus 20.0% (P = .46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT, particularly for skin SR aGVHD.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Adulto , Basiliximab , Criança , Doença Enxerto-Hospedeiro/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Estudos Retrospectivos , Esteroides
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