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1.
Bone Marrow Transplant ; 52(4): 522-531, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27892952

RESUMEN

This study aimed to analyze the use of the revised International Prognostic Scoring System (IPSS-R) assessed after hypomethylating treatment (HMT) for patients with myelodysplastic syndrome (MDS) undergoing an allogeneic stem cell transplantation (SCT). Among 115 patients who received pre-SCT HMT, comparison analysis of the prognostic values between the IPSS-R at the time of HMT (IPSS-R@HMT) and at the time of SCT after HMT (IPSS-R@SCT) showed a significantly higher predictive power for overall survival (OS) of the latter. Alteration in IPSS-R risk occurred in 60%, while the patients with 'down-staged' IPSS-R@SCT showed better OS compared with those with 'unchanged' or 'up-staged' risk. On multivariate analysis in all 201 patients, IPSS-R@SCT, monosomal karyotype, treatment failure to pre-SCT treatment, and high hematopoietic cell transplantation-comorbidity index were independently associated with OS. Constructed using these factors, the MDS Transplantation Prognostic Scoring System (MTPSS) identified four risk groups with 4-year OS of 76.4% in low, 61.4% in intermediate-1 and 21.9% in intermediate-2 risk groups, whereas all in the high risk group died within 2 years after SCT (P<0.001). Our study emphasizes the need for further studies aiming to evaluate a transplantation prognostic model such as the MTPSS to make appropriate decisions for transplantation in MDS.


Asunto(s)
Metilación de ADN/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Anciano , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Comorbilidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Cariotipo , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Medición de Riesgo , Análisis de Supervivencia , Adulto Joven
2.
Bone Marrow Transplant ; 51(11): 1456-1463, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27348538

RESUMEN

Allogeneic stem cell transplantation from HLA-matched siblings (MSD-SCT) for elderly patients with severe aplastic anemia (SAA) is not a widely accepted first-line treatment. Recently, fludarabine, lower-dose cyclophosphamide and antithymocyte globulin conditioning (Flu/lower-dose Cy/ATG) with lower toxicities has been investigated. To determine whether this regimen can overcome the negative effects of age, we analyzed 117 adult patients with SAA who received MSD-SCT using Flu/lower-dose Cy/ATG, and compared outcomes between 63 younger age group (YAG; ⩽40 years) and 54 older age group (OAG; >40 years) patients. No primary graft failure was observed. Neutrophil engraftment was significantly faster in the YAG compared with the OAG (12 vs 13 days; P=0.04). The incidences of acute grade II-IV (9.5% vs 9.3% at day 100; P=0.42) and chronic GVHD (8.1% vs 9.5% at 5 years; P=0.80), secondary graft failure (20.8% vs 7.9% at 5 years; P=0.11) and transplant-related mortality (5.4% and 11.1% at 5 years; P=0.91) were not significantly different between the YAG and OAG. In addition, failure-free (73.7% vs 81.0% at 5 years; P=0.73) and overall survival rates (93.7% vs 88.9% at 5 years; P=0.20) were comparable. Our results suggest that MSD-SCT using Flu/lower-dose Cy/ATG may be a feasible first-line treatment even in older patients with SAA.


Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Factores de Edad , Anemia Aplásica/complicaciones , Anemia Aplásica/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Hermanos , Análisis de Supervivencia , Resultado del Tratamiento , Vidarabina/uso terapéutico , Adulto Joven
3.
Bone Marrow Transplant ; 51(10): 1323-1329, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27214082

RESUMEN

The aim of this study was to evaluate the impact of pretransplant transfusion of packed red cells (PRCs) on outcome after allogeneic stem cell transplantation (SCT) in severe aplastic anemia (SAA). A total of 221 adult SAA patients receiving allogeneic SCT were analyzed. The patients were divided into two groups according to the amount of pretransplant transfusion before SCT: the low transfusion group (⩽32 PRC units, n=164) and the high transfusion group (>32 PRC units, n=57). The incidence of engraftment failure was not different between the two groups. The incidence of acute GvHD (grades II-IV) was higher in the high transfusion group than in the low transfusion group (P=0.04), and the incidences of chronic extensive GVHD were not significantly different (P=0.136). The high transfusion group had higher 5-year transplant-related mortality (TRM) (24.8% vs 6.8%, P<0.001) and lower overall survival (OS) (72.3% vs 91.9%, P<0.001) than those in the low transfusion group. Multivariate analysis revealed that the high transfusion group and unrelated donor type were independent prognostic factors affecting OS. These results indicate that a history of higher pretransplant transfusion of PRCs was associated with increased TRM and decreased OS, suggesting that iron overload had a negative impact on outcome after SCT in SAA.


Asunto(s)
Anemia Aplásica/terapia , Transfusión de Eritrocitos/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad Aguda , Adolescente , Adulto , Anemia Aplásica/complicaciones , Anemia Aplásica/mortalidad , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Sobrecarga de Hierro/etiología , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
5.
Bone Marrow Transplant ; 50(3): 354-62, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25501350

RESUMEN

We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas/uso terapéutico , Factor de Transcripción Ikaros/genética , Piperazinas/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Femenino , Humanos , Factor de Transcripción Ikaros/deficiencia , Factor de Transcripción Ikaros/metabolismo , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Eliminación de Secuencia , Resultado del Tratamiento , Adulto Joven
6.
Bone Marrow Transplant ; 49(6): 773-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24662418

RESUMEN

Few studies are available that compare PBSC and BM from unrelated donors, especially in adult high-risk ALL. To determine which graft source is superior in adult high-risk ALL, we analyzed the long-term outcomes of 106 consecutive transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM). All patients received a uniform strategy of pre-transplant therapy, myeloablative conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC transplants showed outcomes comparable to those of BM transplants for relapse (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes between the two graft sources according to the presence of a Ph chromosome, no significant advantage of PBSC over BM was found in both subgroups of patients. Our data suggest that the outcomes of unrelated donor transplantation are similar between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred graft source for a specific subgroup of adult ALL needs to be further investigated.


Asunto(s)
Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre Periférica , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Terapéutica , Acondicionamiento Pretrasplante , Donante no Emparentado , Adulto Joven
7.
Bone Marrow Transplant ; 48(12): 1562-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23892329

RESUMEN

Hepatic veno-occlusive disease (VOD) remains one of the most severe complications of hematopoietic SCT (HSCT). Anticoagulation and thrombolytic therapies using tissue-plasminogen activator (t-PA) have been used, but are reported to be ineffective and are associated with significant bleeding complications. We analyzed 56 moderate-to-severe post HSCT hepatic VOD cases treated with t-PA. We analyzed clinical outcomes according to the maximal daily dose of t-PA (t-PAmax) and the severity of VOD. Patients were stratified by t-PAmax10 mg (n=37) vs t-PAmax>10 mg (n=19). A higher t-PAmax was associated with increased mortality. Bleeding complications were more likely at higher t-PAmax in both moderate and severe VOD (P=0.036, 0.063), especially if patients had concomitant use of anticoagulants (36.4% vs 13.3%). In moderate VOD, the response rate was 86.4% for t-PAmax10 mg/day and 80% for t-PAmax>10 mg compared with 33.3% and 7.1%, respectively, for severe VOD (P=0.106). The 5-year OS in moderate and severe VOD was 49% and 7%, respectively, and it was 32% for t-PAmax10 mg and 18% for t-PAmax>10 mg. Our data demonstrate that lower bleeding complications and bleeding-related deaths may result from strict limitations on the t-PAmax without concomitant use of anticoagulation therapy. However, the overall response and survival outcomes should be re-evaluated by a well-validated study in the future.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo , Adulto Joven
8.
Bone Marrow Transplant ; 48(4): 587-92, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23000645

RESUMEN

To investigate the risk factors for acute GVHD (aGVHD), based on NIH consensus criteria (NCC), we evaluated 775 patients who underwent allogeneic transplantation. Of them, 346 patients developed aGVHD by NCC, in whom we also analyzed factors affecting aGVHD-specific survival. The cumulative incidence of aGVHD was 44.7%, consisting of classic aGVHD (n=320) and late-onset (n=26). Multivariate analyses revealed that younger age (P=0.015), unrelated donors (P=0.004) and acute leukemia compared with other hematologic malignancies (P=0.005) were significant risk factors for aGVHD, whereas PBSCs showed no association (P=0.720). Multivariate analyses, with only aGVHD patients, revealed that late-onset aGVHD had superior aGVHD-specific survival to classic aGVHD (P=0.044), and identified the association of visceral organ involvement (P=0.002), severity of aGVHD at onset (P=0.035) and advanced disease status (P<0.001) with inferior aGVHD-specific survival. In conclusion, this study demonstrates the risk and prognostic factors for aGVHD by NCC with some differences with the previous reports that were based on old criteria. The difference in the risk factors according to different criteria will give insights about the pathophysiology of GVHD. The better prognosis of late-onset aGVHD than of classic aGVHD raises the necessity for prospective trials with a large cohort focusing on the onset time.


Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre de Sangre Periférica , Enfermedad Aguda , Adolescente , Adulto , Anciano , Consenso , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/fisiopatología , Neoplasias Hematológicas/fisiopatología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo
9.
Bone Marrow Transplant ; 48(5): 678-83, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23128572

RESUMEN

The prognosis for patients with myelodysplastic syndrome with hypomethylating treatment failure (MDS-HTF) has been known to be poor. However, the clinical outcomes and optimal treatment options for secondary AML evolving from MDS-HTF (sAML/MDS-HTF) are not well known. This retrospective analysis was conducted to evaluate the clinical outcomes and influences of treatment options on survival in 46 consecutive patients with sAML/MDS-HTF. The median OS rates were 1.4 months in the best supportive care group (n=15) and 9.4 months in the active treatment group (n=31). One-year OS rates were 13.3% and 36.8%, respectively (P=0.001). Active treatment (P<0.001), lower BM blast (<33%) at sAML (P=0.007), non-poor NCCN (National Cancer Comprehensive Network) cytogenetics (P=0.001) and good performance status (ECOG (Eastern Cooperative Oncology Group) 1) (P=0.024) were significant predictors affecting favorable OS in a multivariate analysis. Of the active treatment options, allo-SCT with prior chemotherapy (CTx) showed better OS compared with CTx only or SCT without CTx (P=0.019). Our analyses suggest that active treatment, particularly SCT following CTx, should be considered in patients with sAML/MDS-HTF if the patient is medically fit.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/cirugía , Síndromes Mielodisplásicos/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/patología , Pronóstico , Tasa de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
10.
Leukemia ; 26(11): 2367-74, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22705993

RESUMEN

We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.


Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Neoplasia Residual , Cromosoma Filadelfia , Piperazinas/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Pirimidinas/uso terapéutico , Adolescente , Adulto , Benzamidas , Terapia Combinada , Femenino , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
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