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1.
Br J Haematol ; 200(5): 608-621, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36370064

RESUMO

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Bussulfano/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Doadores não Relacionados , Irmãos , Estudos Prospectivos , Recidiva Local de Neoplasia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante
2.
Intern Med J ; 53(12): 2341-2345, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38130048

RESUMO

This study aimed to investigate the clinical features of splenomegaly, mainly focussing on cytopenia, in patients with systemic lupus erythematosus (SLE). Cytopenia was commonly observed in 111 SLE patients with splenomegaly (n = 79, 71.2%). During the follow-up period, two patients developed haematologic malignancy after the diagnosis of SLE and splenomegaly, but no patients experienced severe complications (e.g. splenic rupture) related to splenomegaly.


Assuntos
Citopenia , Neoplasias Hematológicas , Lúpus Eritematoso Sistêmico , Humanos , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Neoplasias Hematológicas/complicações
3.
Br J Haematol ; 198(4): 703-712, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35612271

RESUMO

Clonal cytopenia of undetermined significance (CCUS) is characterized by persistent cytopenias with genetic aberrations, which do not meet the diagnostic criteria for myelodysplastic syndrome (MDS). We aimed to compare the clinical and genetic characteristics of CCUS with lower-risk MDS and identify patients with CCUS with a high risk of progression. We performed targeted sequencing of bone marrow (BM) samples from patients with idiopathic cytopenia of undetermined significance (ICUS) (n = 139) and MDS (n = 226). Overall survival (OS) of patients with CCUS (n = 78) was worse than non-clonal ICUS (n = 61) and superior to lower-risk MDS (n = 99). Patients with CCUS showed similar characteristics to those with lower-risk MDS, except for higher haemoglobin, lower BM cellularity, and less frequent SF3B1 mutations. Lower haemoglobin, DDX41 (biallelic germline and somatic), ETV6, and RUNX1 mutations were independent prognostic factors for worse OS. Lower haemoglobin and DDX41 mutations were also associated with lower progression-free survival. Patients with CCUS with high-risk features showed similar or worse OS than patients with lower-risk MDS. Our findings suggest that patients with CCUS having certain clinical or genetic features should be regarded and treated as lower-risk MDS despite lacking significant dysplasia or MDS-associated chromosomal abnormalities.


Assuntos
Hematopoiese Clonal , Síndromes Mielodisplásicas , Aberrações Cromossômicas , Hemoglobinas/genética , Humanos , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética
4.
Haematologica ; 107(2): 510-518, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626862

RESUMO

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.


Assuntos
RNA Helicases DEAD-box , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , RNA Helicases DEAD-box/genética , Etnicidade/genética , Doenças Hematológicas/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Transtornos Mieloproliferativos/genética
5.
Clin Transplant ; 35(3): e14199, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33349948

RESUMO

The prognosis of patients with acute leukemia relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) is dismal. We aimed to evaluate the outcomes and prognostic factors of the second HSCT (HSCT2) in acute leukemia patients relapsed after the first HSCT (HSCT1). We analyzed 80 patients who received HSCT2 for relapsed acute leukemia in two Korean institutes. All but four patients received HSCT2 from a donor other than matched sibling donor: an unrelated donor (URD) in 30 and a familial haploidentical donor (FHD) in 46. Forty-four patients (55.0%) were in complete remission (CR) or CR with incomplete count recovery (CRi) at HSCT2, and the median time from HSCT1 to relapse was 9 months. The 2-year overall survival (OS) and event-free survival (EFS) were 21.0% and 17.5%, respectively. The outcomes were similar between URD and FHD. Multivariate analysis demonstrated that disease status (active disease vs. CR/CRi) at HSCT2 and remission duration after HSCT1 were independent prognostic factors for OS and EFS after HSCT2. HSCT2 from URD or FHD was feasible in patients with acute leukemia relapsed after allogeneic HSCT. Also, our study confirmed two critical prognostic factors; disease status at HSCT2 and remission duration after HSCT1.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Indução de Remissão , Estudos Retrospectivos , Doadores não Relacionados
6.
Mycoses ; 64(9): 1124-1131, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33740824

RESUMO

BACKGROUND AND OBJECTIVES: There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. METHODS: This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. RESULTS: A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n = 24) or BAL fungal culture results (n = 8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193]). CONCLUSION: Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.


Assuntos
Galactose/análogos & derivados , Aspergilose Pulmonar Invasiva , Mananas/análise , Líquido da Lavagem Broncoalveolar/química , Galactose/análise , Galactose/sangue , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/sangue , Resultados Negativos , República da Coreia , Estudos Retrospectivos , Sensibilidade e Especificidade , Centros de Atenção Terciária
7.
J Korean Med Sci ; 36(43): e306, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34751013

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines-BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccine-related ITP is important to promptly initiate appropriate treatment.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Equimose/etiologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Vacinação/efeitos adversos , Idoso , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Dexametasona/uso terapêutico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Índice Periodontal , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , SARS-CoV-2
8.
J Korean Med Sci ; 36(23): e151, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128593

RESUMO

BACKGROUND: This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). METHODS: We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000-September 2017) at our center. RESULTS: Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97-28.0, P < 0.001) and lower CD34⁺ cell dose (RR, 2.44-2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. CONCLUSION: Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/efeitos adversos , Falha de Tratamento , Adulto Jovem
9.
Clin Infect Dis ; 71(8): 1977-1979, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31930297

RESUMO

In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12-99) with positive IGRA results.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tuberculose Latente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Transplante de Células-Tronco/efeitos adversos , Transplantados , Teste Tuberculínico
10.
Ann Hematol ; 99(6): 1231-1239, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382770

RESUMO

Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0-2), moderate (3-5), and high risk (6-8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p < 0.005, Harrell's C-index = 0.84). PIV infection can result in substantial mortality in patients with hematologic malignancy if it progresses to LRTI. The immunodeficiency risk score presented here may be useful for distinguishing moderate and high risk groups that might benefit from antiviral therapy.


Assuntos
Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/mortalidade , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/mortalidade , Adulto , Estudos de Coortes , Feminino , Neoplasias Hematológicas/imunologia , Humanos , Síndromes de Imunodeficiência/imunologia , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Infecções por Paramyxoviridae/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
11.
Eur J Haematol ; 105(3): 262-273, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32353911

RESUMO

OBJECTIVES: We evaluated the prognostic impact of MK on postremission outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) in the first complete remission (CR1). METHODS: We retrospectively analyzed 465 adult patients with AML who had received HSCT in the first CR between 2000 and 2016. RESULTS: In MK + AML, the median leukocyte count was significantly lower (P < .001) and no NPM1 mutation was found (P = .042). Multivariate analysis revealed that MK was the most powerful prognostic factors for OS (hazard ratio [HR], 2.6; P = .001), EFS (HR, 3.8; P < .001), and cumulative incidence of relapse (HR, 6.1; P < .001), compared to any other poor risk factors such as complex karyotype, FLT3-ITD mutations, old age, and higher leukocyte count. The adverse prognostic impact of MK tended to be more prominent in the younger age group (<40 years) (HR, 6.3, P < .001) than in the older age group (≥40 years) (HR, 3.4, P < .001). CONCLUSION: Novel treatment modalities for MK + AML need to be investigated to reduce the risk of relapse after HSCT.


Assuntos
Cariótipo Anormal , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Monossomia , Adolescente , Adulto , Idoso , Aberrações Cromossômicas , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
12.
Biol Blood Marrow Transplant ; 25(6): 1116-1121, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30508593

RESUMO

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m2) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m2/day on days -6 to -2 and melphalan at 100 mg/m2 on day -2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Melfalan/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Melfalan/farmacologia , Pessoa de Meia-Idade , Agonistas Mieloablativos/farmacologia , Análise de Sobrevida , Vidarabina/farmacologia , Vidarabina/uso terapêutico , Adulto Jovem
13.
Acta Haematol ; 139(4): 220-227, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29860259

RESUMO

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.


Assuntos
Medula Óssea/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Exame de Medula Óssea , Terapia Combinada , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
14.
Biol Blood Marrow Transplant ; 23(9): 1555-1566, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28552421

RESUMO

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.


Assuntos
Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Mieloma Múltiplo/terapia , Vidarabina/análogos & derivados , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Teste de Histocompatibilidade , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Agonistas Mieloablativos/uso terapêutico , Estudos Prospectivos , Recidiva , Indução de Remissão , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico , Doadores não Relacionados , Vidarabina/uso terapêutico
15.
Biol Blood Marrow Transplant ; 22(11): 2065-2076, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27530969

RESUMO

The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).


Assuntos
Células Matadoras Naturais/transplante , Leucemia/terapia , Transplante Haploidêntico/métodos , Doença Aguda , Adulto , Idoso , Feminino , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/métodos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Doadores de Tecidos , Adulto Jovem
16.
Ann Hematol ; 95(7): 1151-61, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27106699

RESUMO

Reduced-intensity conditioning (RIC) regimens can cause decreased non-relapse mortality (NRM) but lead to higher relapse rates in higher-risk myelodysplastic syndrome (MDS). However, relapse is not the main problem after hematopoietic cell transplantation (HCT) in lower-risk MDS, and post-transplant outcomes may therefore improve with less intense non-myeloablative conditioning (NMC) regimens. We here report the results of a single-center feasibility study of NMC with cyclophosphamide-fludarabine-antithymocyte globulin (CyFluATG) in MDS patients with bone marrow blasts <5 %. We compared post-transplant outcomes between CyFluATG and a RIC regimen, busulfan-fludarabine-antithymocyte globulin (BuFluATG). Fifteen MDS patients received allogeneic HCT after CyFluATG conditioning comprising cyclophosphamide (100 mg/kg), fludarabine (150 mg/m(2)), and ATG, and 30 MDS historical control patients received BuFluATG conditioning which contained busulfan (8 [oral] or 6.4 [i.v.] mg/kg), fludarabine, and ATG. The 4-year overall survival (OS) and NRM rates were 80.0 and 20.0 % for CyFluATG and 73.3 and 20.0 % for BuFluATG, respectively. Neutrophil and platelet engraftment was significantly faster with CyFluATG than BuFluATG (median 12 vs. 14 days, P = 0.005 for neutrophils; median 15 vs. 21 days, P = 0.032 for platelets). CyFluATG produced a faster immune reconstitution of T-cells at 1 month after HCT than BuFluATG. Fertility was maintained after HCT with CyFluATG. In conclusion, the CyFluATG regimen is feasible in lower-risk MDS patients in terms of adequate engraftment and low NRM.


Assuntos
Células da Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Células da Medula Óssea/efeitos dos fármacos , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/métodos , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
18.
Biomol Ther (Seoul) ; 31(3): 319-329, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36382510

RESUMO

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

19.
Korean J Intern Med ; 38(5): 734-746, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37334511

RESUMO

BACKGROUND/AIMS: We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). METHODS: Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. RESULTS: In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. CONCLUSION: The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Rituximab/efeitos adversos , Estudos Prospectivos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
20.
Leukemia ; 37(4): 807-819, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36932165

RESUMO

Clinical effect of donor-derived natural killer cell infusion (DNKI) after HLA-haploidentical hematopoietic cell transplantation (HCT) was evaluated in high-risk myeloid malignancy in phase 2, randomized trial. Seventy-six evaluable patients (aged 21-70 years) were randomized to receive DNKI (N = 40) or not (N = 36) after haploidentical HCT. For the HCT conditioning, busulfan, fludarabine, and anti-thymocyte globulin were administered. DNKI was given twice 13 and 20 days after HCT. Four patients in the DNKI group failed to receive DNKI. In the remaining 36 patients, median DNKI doses were 1.0 × 108/kg and 1.4 × 108/kg on days 13 and 20, respectively. Intention-to-treat analysis showed a lower disease progression for the DNKI group (30-month cumulative incidence, 35% vs 61%, P = 0.040; subdistribution hazard ratio, 0.50). Furthermore, at 3 months after HCT, the DNKI patients showed a 1.8- and 2.6-fold higher median absolute blood count of NK and T cells, respectively. scRNA-sequencing analysis in seven study patients showed that there was a marked increase in memory-like NK cells in DNKI patients which, in turn, expanded the CD8+ effector-memory T cells. In high-risk myeloid malignancy, DNKI after haploidentical HCT reduced disease progression. This enhanced graft-vs-leukemia effect may be related to the DNKI-induced, post-HCT expansion of NK and T cells. Clinical trial number: NCT02477787.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Interleucina-15 , Doença Enxerto-Hospedeiro/patologia , Células Matadoras Naturais/patologia , Progressão da Doença , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patologia , Condicionamento Pré-Transplante
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