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1.
Blood Adv ; 3(21): 3406-3418, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

2.
Biol Blood Marrow Transplant ; 25(8): 1629-1636, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048087

RESUMO

Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.

3.
Ann Hematol ; 98(7): 1733-1742, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053879

RESUMO

Hepatic sinusoidal obstruction syndrome (SOS) has been rarely studied after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective multicentre study on patients with SOS after allo-HSCT in China. The incidence, risk factors, and outcomes were compared between HID HSCT and matched related donor (MRD) HSCT. SOS developed in 0.4% of patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1-55) after allo-HSCT (HIDs: 24 days, MRDs: 20 days, p = 0.316). For patients diagnosed with SOS, the 2-year cumulative incidence of relapse was 22.7% and 22.4% in patients receiving HID and MRD transplantation, respectively (p = 0.584). Overall survival (OS) at 2 year was 10.4% and 38.5% in the two groups (p = 0.113). The transplant-related mortality (TRM) at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analyses, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and advanced disease status at the time of HSCT (p = 0.009). The outcomes of SOS after HID HSCT are similar to those after MRD HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doadores de Tecidos , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , China/epidemiologia , Feminino , Seguimentos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
7.
Bone Marrow Transplant ; 54(9): 1462-1470, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30710101

RESUMO

Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.

8.
Biol Blood Marrow Transplant ; 25(6): 1210-1217, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30708190

RESUMO

Haploidentical transplantations have achieved comparable survival as HLA fully matched unrelated donors (URDs). When choosing the best donor for HLA haploidentical transplantations, most institutions prioritize using young male donors over mother donors. In a retrospective study we compared outcomes in mother donor and URD transplantations. We found that both 2-year overall survival and 2-year leukemia-free survival were comparable between the mother donor group and URD group (74.8% versus 72.9%, P = .937, and 71.7% versus 67.0%, P = .580, respectively). Higher incidences of grades II to IV acute graft-versus-host disease (GVHD) and chronic GVHD were observed in the mother donor group than in the URD group (43.5% versus 14.0%, P = .001, and 62.2% versus 38.7%, P = .007, respectively). The 2-year cumulative incidences of relapse were significantly decreased in the mother donor group (7.6% versus 20.9%, P = .036). These findings suggest mother donor transplantations could achieve comparable survival with URD transplantations and exhibited decreased rates of relapse but increased rates of GVHD, indicating that mother donors would be a suitable choice for patients without an identical sibling donor.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30518981

RESUMO

This study investigated the prognostic factors in patients (n = 89) who experienced relapse and received chemotherapy plus donor leukocyte infusion (Chemo-DLI) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Patients with early relapse (< 6 vs. > 6 months after haplo-HSCT), higher bone marrow blast count before chemo-DLI (> 20% vs. 5-19%), and without chronic graft-versus-host disease (cGVHD) after chemo-DLI had a higher rate of progressive disease (PD) and worse progression-free survival (PFS) and overall survival (OS). In multivariate analysis, non-cGVHD after Chemo-DLI and high blast count predicted a higher risk of PD and poorer PFS, and non-cGVHD after Chemo-DLI and early relapse predicted poorer OS. The patients were stratified into three groups according to these three risk factors. Patients with all three risk factors (n = 14) had the highest PD rate and poorest survival compared with those with one or two risk factors (n = 63) or no risk factors (n = 12). Thus, early relapse, high leukemia burden before Chemo-DLI, and non-cGVHD after Chemo-DLI can predict outcomes in patients who have experienced relapse and received Chemo-DLI after haplo-HSCT. New therapeutic strategies should be identified for these patients.

10.
Clin Cancer Res ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478089

RESUMO

PURPOSE: Although myeloablative human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant ATG and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors(MSDs), the effect of haplo-HSCT on postremission treatment of patients with AML with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. EXPERIMENTAL DESIGN: In this prospective trial, among 443 consecutive patients aged 16-60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n=69) or underwent haplo-HSCT (n=78). RESULTS: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs 47.3%, P=0.0004 and 80.8% vs 53.5%, P=0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs chemotherapy) was an independent risk factor affecting the LFS (HR 0.360, 95% CI 0.163-0.793, P=0.011), OS (HR 0.361, 95% CI 0.156-0.832, P=0.017) and cumulative incidence of relapse (CIR; HR 0.161, 95% CI 0.057-0.459, P=0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. CONCLUSIONS: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of MSDs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30485788

RESUMO

The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI) associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 104). The 5-year cumulative incidence of complete remission (CR) after Chemo-DLI was 81.0% (95% CI, 73.3-88.7%) and 84.6% (95% CI, 74.5-94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD 40.9% (95% CI, 29.3-52.5%) and non-cGVHD groups 29.2% (95% CI 23.1-35.3%). The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2-70.2%) and 34.6% (95% CI, 15.3-78.2%) in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of mild cGVHD 9.1% (95% CI, 2.4-34.1%) and non-cGVHD groups 8.3% (95% CI 3.3-21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9-82.7%) and 43.1% (95% CI, 22.1-84.0%), in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD 9.1% (95% CI 1.8-47.1%) and non-cGVHD groups 14.9% (95% CI, 7.3-30.2%). Our observations highlight the close relation between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.

12.
Ann Hematol ; 97(8): 1399-1406, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29568992

RESUMO

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and effective therapy for hematology patients, but it usually has many complications, such as neurological complications. As one of the neurological complications following haplo-HSCT, immune-mediated demyelinating diseases of the central nervous system (CNS) seriously affect a patient's quality of life. However, the incidence, risk factors, and pathogenesis of CNS demyelination are not very well understood. Thirty of the 1526 patients (1.96%) suffered from CNS demyelination. In univariate analysis, we found that blood-brain barrier (BBB) permeability and the CSF IgG synthesis index (IgG-Syn) were related to the occurrence of CNS demyelination (p < 0.05). In a multivariate analysis, the IgG-Syn (OR = 1.017, 95% CI 1.003-1.031, p = 0.019) and CSF anti-myelin oligodendrocyte glycoprotein antibody (MOG.Ab) (OR = 12.059, 95% CI 1.141-127.458, p = 0.038) were independently associated with the onset of CNS demyelination. We also studied the possible pathogenesis of CNS demyelination. Immune reconstitution (the cell proportions of CD19+ B cells, CD3+ T cells, and CD4+ T cells); the counts of leucocytes, lymphocytes, monocytes, and platelets; and the levels of immunoglobulins A, G, and M 30, 60, and 90 days after HSCT showed no significant differences between CNS demyelination and no demyelination (p > 0.05). The probabilities of overall survival showed no significant differences between patients with and without demyelination (p > 0.05). Only four deaths in 30 patients, but bringing projected survival to less than 20%.We imply that IgG-Syn and CSF MOG. Ab may be associated with the onset of CNS demyelination during 2 weeks of neurological symptoms in patients with brain or spinal cord MRI abnormality. Immune reconstitution may not be the pathogenesis of CNS demyelination.


Assuntos
Formação de Anticorpos/imunologia , Autoanticorpos/imunologia , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/imunologia , Transplante de Células-Tronco Hematopoéticas , Imunoglobulina G/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Adolescente , Adulto , Autoanticorpos/líquido cefalorraquidiano , Criança , Doenças Desmielinizantes/mortalidade , Doenças Desmielinizantes/terapia , Feminino , Haplótipos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Prognóstico , Irmãos , Transplante Homólogo , Adulto Jovem
13.
Ann Hematol ; 97(7): 1209-1217, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29532160

RESUMO

We aimed to evaluate the treatments, particularly the role of corticosteroids, in patients with late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). One hundred and sixty-three consecutive patients who underwent non-T-cell-depleted allo-HSCT and met the criterion of LOHC after allo-HSCT were enrolled in this study. The median time from allo-HSCT to the occurrence of LOHC was 29 (range, 4-155) days. Pathogens identified in blood and/or urine samples from 143 patients were mostly viruses. All of the patients with LOHC received intravenous fluid hydration, alkalization, and forced diuresis, of which 2 patients achieved complete remission (CR) after these treatments. The remaining 161 patients received anti-infection therapies and 71 achieved CR after the therapies. Corticosteroids were additionally applied to 83 out of 90 patients who did not achieve CR after anti-infection therapies, and 88.0% (n = 73) of them showed a grade 3 to 4 LOHC at the beginning of corticosteroid therapy. Thirty-five patients showed an immediate response (CR or downgraded at least one grade) within 1 week after the beginning of the corticosteroid therapy. Sixty-four patients (77.1%) achieved CR after corticosteroid therapy, and the median period from the beginning of corticosteroid therapy to CR was 17 days. Thus, we observed that viruses were the most common pathogens in LOHC after allo-HSCT and that anti-infection therapies were critical. For patients not showing a satisfactory response to anti-infection therapies, additional corticosteroid therapy may help to achieve CR.


Assuntos
Corticosteroides/uso terapêutico , Cistite/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Hematúria/tratamento farmacológico , Viroses/complicações , Doença Aguda , Adolescente , Adulto , Aloenxertos , Antivirais/uso terapêutico , Criança , Terapia Combinada , Cistite/etiologia , Diuréticos/uso terapêutico , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Hidratação , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Viroses/tratamento farmacológico , Adulto Jovem
14.
Chin J Integr Med ; 24(6): 423-428, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28634863

RESUMO

BACKGROUND: Acupuncture can not only be used for well-known diseases, but also for so-called modern lifestyle-related diseases. Using innovative methods like e.g. new analyses of heart rate variability (HRV), it is also possible to investigate diseases like burnout syndrome, ie., qi deficiency in Chinese medicine (CM). OBJECTIVE: The main object of this research protocol is to perform research on the relationship of burnout syndrome and heart rate (HR) and HRV. METHODS: A total of 175 patients with burnout syndrome (qi deficiency syndrome) in five groups and 35 healthy volunteers will be investigated. Based on random numbers generated by computer and concealed in opaque envelops, the patients will be assigned to four acupuncture groups using Zusanli (ST 36) acupuncture stimulation, Guanyuan (CV4) acupuncture stimulation, both points, and both points with Streitberger device respectively, and a moxibustion group using both points mentioned above, with 35 cases in each group. Altogether four different experiments are planned. Experiment 1 includes 70 subjects and is a comparison between a burnout group and a control group (healthy volunteers). The evaluation parameters are different scores and indices of HR and HRV. Experiment 2 includes 140 subjects and compares the efficacy of different acupuncture points. In experiment 3 (105 subjects), acupuncture and moxibustion should be compared to healthy volunteers. Experiment 4 (70 subjects) investigates the long-term therapeutic effects of acupuncture and moxibustion on the scores of qi deficiency and HR/HRV in qi deficiency patients. In both the acupuncture and moxibustion groups, a total of 10 treatments will be performed. CONCLUSIONS: The joint research aims at the scientific evaluation of CM, mainly in the field of HRV. This parameter could be a very good indicator of the state of health and can be inflfluenced by different acupuncture methods, as shown in the past.


Assuntos
Terapia por Acupuntura , Frequência Cardíaca/fisiologia , Estilo de Vida , Projetos de Pesquisa , Adulto , Áustria , Esgotamento Profissional/terapia , China , Feminino , Humanos , Moxibustão
15.
Eur J Haematol ; 100(2): 171-181, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29114931

RESUMO

OBJECTIVES: To explore the possible risk factors for the occurrence and mortality of thrombotic microangiopathy (TMA) with concomitant acute graft-vs-host disease (aGVHD) and to investigate outcomes and treatments of this disorder after allo-HSCT. METHODS: Fifty cases diagnosed with TMA with concomitant aGVHD and 150 controls were identified from a cohort composed of 3992 patients who underwent allo-HSCT from 2008 to 2016. RESULTS: Grade III-IV aGVHD (P = .000), acute kidney injury (AKI) (P = .033), and hypertension (P = .028) were significant independent risk factors associated with the occurrence of TMA with concomitant aGVHD. A haptoglobin level below normal (P = .013), a maximum volume of diarrhea >2500 mL/d (P = .015), and bloody diarrhea (P = .049) were significant markers for death in both univariate and multivariate analyses. Patients diagnosed with TMA with concomitant aGVHD had a lower overall survival (OS), a higher non-relapse mortality (NRM), but a lower risk of relapse. CONCLUSIONS: Thrombotic microangiopathy with concomitant aGVHD is a significant complication after allo-HSCT, with a worse outcome, including significantly lower OS and higher NRM. There are specific risk factors associated with occurrence and mortality of this complication.


Assuntos
Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia , Doença Aguda , Adolescente , Adulto , Criança , Feminino , Seguimentos , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/terapia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
16.
Biol Blood Marrow Transplant ; 23(12): 2143-2150, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28865971

RESUMO

This study aimed to validate the capability of the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic scoring system to predict outcomes of patients with myelodysplastic syndromes (MDS) who had undergone HLA-haploidentical related donor hematopoietic stem cell transplantation (haplo-HSCT). We also propose and validate a more suitable prognostic scoring system. A total of 157 patients with MDS who underwent haplo-HSCT were enrolled. The CIBMTR prognostic scoring system could predict the 2-year clinical outcomes, but failed to predict the 100-day clinical outcomes after haplo-HSCT. Our multivariable model identified 2 independent predictors of overall survival: age and monosomal karyotype (MK). Weighted scores of 5, 3, and 2 were assigned to age ≥50 years, age 30 to 49 years, and MK, respectively, and a 2-category system was created: low (score ≤3) and high (score >3). Our refined prognostic scoring system can predict both the 100-day and 2-year clinical outcomes after haplo-HSCT. Our findings indicate that the CIBMTR prognostic scoring system is predictive of the outcomes of patients with MDS following haplo-HSCT, and that older patients with MDS and/or patients with MK should be closely monitored after haplo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Análise de Sobrevida , Transplante Haploidêntico/mortalidade , Adulto Jovem
17.
Biol Blood Marrow Transplant ; 23(8): 1303-1310, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28457953

RESUMO

The efficacy of minimal residual disease (MRD)-directed IFN-α treatment was investigated in acute leukemia patients who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 107). MRD-positive status was defined as positivity for leukemia-associated aberrant immune phenotypes or positivity for Wilms' tumor gene 1 in a single bone marrow sample. Recombinant human IFN-α-2b injections were administered subcutaneously 2 to 3 times per week for 6 months. The 2-year cumulative incidence of severe acute and chronic graft-versus-host disease after IFN-α treatment was 5.7% and 6.6%, respectively. Eighty-one patients (75.7%) turned MRD-negative after IFN-α treatment 1 month (42; 39.3%), 2 months (6; 5.6%), 3 months (7; 6.5%), and >3 months (26; 24.3%) after MRD-directed IFN-α treatment. Twelve patients showed relapse after IFN-α treatment, and 7 died of relapse. Four patients died of nonrelapse mortality (NRM). The 2-year cumulative incidence of relapse, relapse mortality, and NRM after IFN-α treatment was 11.5%, 6.8%, and 4.3%, respectively. The 2-year probabilities of event-free survival, disease-free survival, and overall survival after IFN-α treatment were 66.5%, 82.4%, and 87.4%, respectively. Persistent MRD after IFN-α treatment was significantly associated with higher relapse risk and poorer survival. Thus, MRD-directed IFN-α treatment is effective for patients who were MRD-positive after allo-HSCT. The study was registered at http://clinicaltrials.gov as NCT02185261.


Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Interferon-alfa/administração & dosagem , Leucemia/mortalidade , Leucemia/terapia , Sistema de Registros , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Taxa de Sobrevida , Fatores de Tempo
18.
Cancer ; 123(15): 2881-2892, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28301690

RESUMO

BACKGROUND: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown. METHODS: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations. RESULTS: A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS. CONCLUSIONS: ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92. © 2017 American Cancer Society.


Assuntos
Soro Antilinfocitário/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Fatores Imunológicos/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Ann Hematol ; 96(5): 829-838, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28285386

RESUMO

The efficacy of donor lymphocyte infusion (DLI) without chemotherapy was investigated and compared with that of chemotherapy prior to DLI (Chemo-DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). We enrolled 115 consecutive patients who received either DLI (n = 20) or Chemo-DLI (n = 95) during the same period. For each DLI recipient, three recipients matched for age at the HSCT, underlying diseases, and the year of the HSCT were randomly selected from the Chemo-DLI cohort (n = 60). The 2-year cumulative incidence of severe acute graft-versus-host disease (GVHD) and chronic GVHD was comparable between the groups. Fifteen (75.0%) and 47 (78.3%) patients in the DLI and Chemo-DLI groups turned MRD-negative, respectively. The 2-year cumulative incidences of relapse and non-relapse mortality after intervention were 30.7 versus 39.6% (P = 0.582) and 10.3 versus 6.0% (P = 0.508) in the DLI and Chemo-DLI groups, respectively. The 2-year probabilities of disease-free, overall, and GVHD-free/relapse-free survival after preemptive intervention were 58.9 versus 54.3% (P = 0.862), 69.3 versus 78.1% (P = 0.361), and 44.4 versus 35.1% (P = 0.489) in the DLI and Chemo-DLI groups, respectively. In multivariate analysis, the intervention method did not significantly influence the clinical outcomes. In summary, preemptive DLI alone may be effective for patients who are MRD-positive and may be a potential alternative for patients who refuse or are unable to receive Chemo-DLI after HSCT.


Assuntos
Leucemia/diagnóstico , Leucemia/terapia , Transfusão de Linfócitos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Neoplasia Residual/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Humanos , Leucemia/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
20.
J Hematol Oncol ; 10(1): 44, 2017 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-28166825

RESUMO

BACKGROUND: The optimal monitoring schedules and cutoff minimal residual disease (MRD) levels for the accurate prediction of relapse at all time points after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with t(8;21) acute myeloid leukemia (AML). METHODS: RUNX1-RUNX1T1 transcript levels were measured in bone marrow samples collected from 208 patients at scheduled time points after transplantation (1530 samples in total). RESULTS: A total of 92.3% of the requested samples were collected, and 74.0% of patients had complete sample collection. The 1-, 3-, and 6-month RUNX1-RUNX1T1 transcript levels could significantly discriminate between continuous complete remission and a hematologic relapse at 1.5-3, 4-6, and 7-12 months but not at >3, >6, and >12 months, respectively. Over 90% of the 175 patients who were in continuous complete remission had a ≥3-log reduction in RUNX1-RUNX1T1 transcript levels from the time of diagnosis at each time point after transplantation and a ≥4-log reduction at ≥12 months. A <3-log reduction within 12 months and/or a <4-log reduction at ≥12 months was significantly related to a higher 3-year cumulative incidence of relapse (CIR) rate in both the entire cohort and the patients with no intervention after HSCT (58.4 vs. 2.2%, 76.5 vs. 2.0%; all P < 0.0001). Patients who had received a preemptive donor lymphocyte infusion when the increase in RUNX1-RUNX1T1 transcripts was ≤1-log according to the above dual cutoff values had significantly lower 1-year CIR rate after intervention than the patients who had received an infusion when the increase was >1-log (0 vs. 55.0%, P = 0.015). CONCLUSIONS: RUNX1-RUNX1T1 transcripts with a <3-log reduction from diagnosis within 12 months and/or a <4-log reduction at ≥12 months after allo-HSCT could accurately predict relapse and may prompt a timely intervention in patients with t(8;21) AML.


Assuntos
Cromossomos Humanos Par 21/ultraestrutura , Cromossomos Humanos Par 8/ultraestrutura , Subunidade alfa 2 de Fator de Ligação ao Core/biossíntese , Regulação Leucêmica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Proteína 1 Parceira de Translocação de RUNX1/biossíntese , Translocação Genética , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 8/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Proteínas de Fusão Oncogênica/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Recidiva , Adulto Jovem
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