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1.
Int J Cancer ; 139(9): 2106-15, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27356906

RESUMEN

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children (n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively (p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively (p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively (p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia Local de Neoplasia/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Análisis de Supervivencia , Resultado del Tratamiento
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1123-1126, 2020 Aug.
Artículo en Zh | MEDLINE | ID: mdl-32798386

RESUMEN

OBJECTIVE: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML). METHODS: The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis. RESULTS: Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival,and no patient relapsed. CONCLUSION: UCBT is an effective treatment for children with JMML.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Juvenil , Niño , Preescolar , Humanos , Lactante , Masculino , Estudios Retrospectivos , Acondicionamiento Pretrasplante
3.
Infect Drug Resist ; 13: 373-383, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32104009

RESUMEN

INTRODUCTION: Current consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited. PATIENTS AND METHODS: Wct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies <1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls. RESULTS: The results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07-0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8+ T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20×109/L vs 0.10×109/L, p=0.021, respectively). CONCLUSION: DNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8+ T cells.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1633-1640, 2019 Oct.
Artículo en Zh | MEDLINE | ID: mdl-31607325

RESUMEN

OBJECTIVE: To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT). METHODS: Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation. RESULTS: The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×109 /L vs 0.25×109 /L, P=0.015 and 2.53×109 /L vs 1.36×109 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8+ T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×109 /L vs 0.10×109 /L, P=0.038 and 1.62×109 /L vs 0.68×109 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively. CONCLUSION: The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8+ T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Trasplante de Células Madre Hematopoyéticas , Reconstitución Inmune , Linfocitos T CD8-positivos , Citomegalovirus , ADN , Humanos
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1246-1252, 2019 Aug.
Artículo en Zh | MEDLINE | ID: mdl-31418388

RESUMEN

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen,and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×107/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×105/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)>0.5×109/L and platelet 20×109/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION: UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Leucemia Mieloide Aguda , Trasplante de Células Madre de Sangre Periférica , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Humanos , Ácido Micofenólico , Proteínas de Fusión Oncogénica , Proteína 1 Compañera de Translocación de RUNX1 , Acondicionamiento Pretrasplante
6.
Hematology ; 23(2): 96-104, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28795658

RESUMEN

BACKGROUND: Double-unit cord blood transplantation (CBT) can be used to overcome the limitation of single-unit CBT with low cell content for adults and larger adolescents. However, whether double-unit CBT is superior to single-unit CBT remains controversial. METHODS: We reviewed the medical records of 228 consecutive hematological malignancies who received CBT between November 2005 and December 2013. Ninety-seven eligible patients met the criteria (age ≥14 years and body weight ≥50kg) and were enrolled in this study. RESULTS: The incidence of myeloid engraftment in the double-unit CBT group was significantly lower that in the single-unit CBT group (89.2 vs. 96.7%) (p = 0.026), and the incidence of platelet engraftment in the double-unit CBT group was slightly lower (70.3 vs. 86.7%) (p = 0.057). The 5-year transplant-related mortality rate was significantly higher in the double-unit CBT group when compared with that of the single-unit CBT group [54.1 vs. 33.3%, p = 0.026]. The 5-year probabilities of overall survival, disease-free survival and graft-versus-host disease (GVHD) -free/relapse-free survival in the double-unit CBT group were significantly lower than that of the single-unit CBT group (37.8 vs. 56.7%, p = 0.037; 32.4 vs. 55.0%, p = 0.017; 24.3 vs. 50.0%, p = 0.006). The incidences of GVHD and relapse were similar. CONCLUSIONS: For adolescent and adult hematological malignancies with heavier body weight (≥50kg), double-unit CBT has an inferior clinical outcome when compared with single-unit CBT having a sufficient cell dose. Double-unit CBT should only reserve for patients who need an urgent transplant but lacking of a related or unrelated donor and without an adequately dosed single CB.


Asunto(s)
Peso Corporal , Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia
7.
Zhonghua Nei Ke Za Zhi ; 46(3): 224-8, 2007 Mar.
Artículo en Zh | MEDLINE | ID: mdl-17547807

RESUMEN

OBJECTIVE: To monitor the gene expression of BCR/ABL in chronic myeloid leukemia patients after allogeneic hematopoietic stem cells transplantation with real-time RT-PCR for evaluating therapeutic efficacy and guiding further treatment. METHODS: Taqman real-time RT-PCR technique was performed to monitor peripheral blood BCR/ABL transcript levels in 10 patients at the time of diagnosis and serially at intervals in 25 patients after allogeneic hematopoietic stem cells transplantation. beta-actin mRNA was used as an endogenous reference. RESULTS: The sensitivity of real-time RT-PCR was 10 copies/microl. In 15 patients receiving transplantation, the median of N(BCR/ABL) (%) before transplantation, 1 month after transplantation and 2 months after transplantation was respectively: 6.57 (0.14 - 38.83), 0.10 (0 - 1.71) and 0 (0 - 0.52). 3 months later N(BCR/ABL) (%) all turned to 0. BCR/ABL transcripts after transplantation were detected to decrease gradually. N(BCR/ABL) (%) 1 month after transplantation and 2 months after transplantation was both lower than that before transplantation (chi(2) both = 13.07, P < 0.01). N(BCR/ABL) (%) at 2 months after transplantation was lower than that at 1 month after transplantation (chi(2) = 8.10, P < 0.01). In 10 other patients, N(BCR/ABL) (%) was 0 in consecutive tests from 3 to 43 months after transplantation. CONCLUSION: Real-time RT-PCR is sensitive, reliable and reproducible for monitoring CML relapse after transplantation. It is of help in detecting minimal residual disease, predicting the prognosis of the disease and providing practical indications for further treatment.


Asunto(s)
Proteínas de Fusión bcr-abl/biosíntesis , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Adolescente , Adulto , Niño , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(2): 440-6, 2014 Apr.
Artículo en Zh | MEDLINE | ID: mdl-24763020

RESUMEN

This study was purposed to comparatively analyze the early T-lymphocyte subsets and T-cell receptor excision cycles (TREC) reconstruction in recipients with hematologic malignancies after myeloablative unrelated cord blood transplantation (UCBT) and sibling donor bone marrow and/or peripheral blood stem cell transplantation (BMT/PBSCT). The peripheral blood T lymphocyte subsets were detected using flow cytometry and TREC were detected using real-time quantitative PCR for 40 patients with hematologic malignancies in the first six months after myeloablative allogenic hematopoietic stem cell transplantation. The results showed that in the first month after transplantation, the absolute counts of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+) cells were lower significantly in the UCBT group than those in the BMT/PBSCT group. And later the absolute counts of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) cells were not different between two groups. The ratio of CD3(+)T subset in the peripheral blood lymphocytes of the UCBT recipients was lower, but the difference was not statistically significant within 2 months after transplantation. The ratio of CD3(+)CD4(+) cells in the patients received the UCBT and BMT/PBSCT decreased obviously since engraftment happened. The CD3(+)CD4(+) cells on the 2 months after transplantation fell to the lowest level, then gradually increased, but did not reach to the normal level until 6 months after transplantation. CD3(+)CD8(+)cells were well reconstituted, rising to normal at the engraftment after transplantation, with a low CD4(+): [KG-*2] CD8(+) ratio over the first 6 months after transplantation. Compared with the BMT/ PBSCT group, the naive T cells (CD3(+)CD4(+)CD45RA(+)CD62L(+)) were more in the first month after transplantation and the terminally differentiated effector memory T cells (CD3(+)CD4(+)CD45RA(+)CD62L(-)) were more at the 3 month after transplantation in the UCBT group, and those were significantly more than the normal control group. TREC were lower and did not recovered until 6 months after transplantation in the recipients of the two groups. It is concluded that compared with sibling donor's BMT/PBSCT, early T cell reconstitution significantly delayed after UCBT, but the terminally differentiated effector memory T cells are higher after transplantation, and thus play a anti-infective or anti-leukemia role.


Asunto(s)
Sangre Fetal/trasplante , Trasplante de Células Madre Hematopoyéticas/métodos , Receptores de Antígenos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven
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