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1.
Cancer Sci ; 115(6): 2002-2011, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38498976

RESUMO

Triplet regimen comprising proteasome inhibitors, immunomodulatory drugs, and dexamethasone (DEX) is a recommended induction/consolidation therapy for multiple myeloma (MM) patients eligible for transplant. In this Japanese phase II study conducted from 2017 to 2019, newly diagnosed MM patients aged 20-65 received four induction cycles with bortezomib (Bor), lenalidomide (Len), and DEX (VRD), followed by Bor and high-dose melphalan with autologous stem cell rescue. Subsequently, they underwent four consolidation cycles with carfilzomib, Len, and DEX (KRD), followed by Len maintenance until disease progression. A total of 141 patients were analyzed. In an intent-to-treat population, the complete or better response post induction was 19.9%, rising to 39.7%, 58.9%, and 62.4% after transplant, consolidation, and 1-year maintenance, respectively. With a median follow-up of 38 months, the 3-year progression-free survival (PFS) rate was 83.5% and the 3-year overall survival rate was 92.5%. Severe adverse events (≥grade 3) occurred in ~30% of patients; however, there was no treatment-related mortality. These findings clearly showed the tolerability and effectiveness of this protocol. Nevertheless, patients with high-risk cytogenetics showed a trend toward lower 3-year PFS than those without (77.8% vs. 89.4%, p = 0.051), and ultra-high-risk cytogenetics (≥2 high-risk cytogenetics) had an even worse prognosis, with 61.2% 3-year PFS. To overcome this situation, a more potent treatment strategy incorporating novel agents such as the CD38-antibody should be assessed in future studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Transplante de Células-Tronco Hematopoéticas , Lenalidomida , Mieloma Múltiplo , Transplante Autólogo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Quimioterapia de Consolidação/métodos , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Oligopeptídeos/uso terapêutico , Oligopeptídeos/administração & dosagem , Quimioterapia de Indução/métodos , Intervalo Livre de Progressão , Adulto Jovem , Quimioterapia de Manutenção/métodos
2.
Eur J Haematol ; 111(1): 103-112, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36991564

RESUMO

OBJECTIVE: The prognostic significance of IKZF1plus in adult Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients had remained to be clarified. METHODS: We conducted a prospective, multicenter study, the ALL/MRD2008 trial, and investigated the clinical significance of IKZF1plus . RESULTS: From December 2008 to November 2013, 38 untreated Ph+ ALL patients were enrolled. At the end of the induction, 97.4% of patients (37/38) achieved complete hematological remission, with MRD-negativity of 48.6% (18/37). There were 19 patients with IKZF1plus , 13 with IKZF1 deletion alone (ΔIKZF1) and 4 with no IKZF1 deletions (no ΔIKZF1). The probability of 3-year DFS and OS in these Ph+ ALL patients were 50% (95% confidence interval [CI], 33-65) and 55% (95% CI, 38-69), respectively. There was no significant difference between IKZF1plus , ΔIKZF1, and no ΔIKZF1 in DFS (47%, 54%, 75% [p = .63]) or OS (47%, 62%, NA [p = .39]). CONCLUSIONS: We revealed no relationship between IKZF1plus status and survival outcomes in Ph+ ALL patients treated with imatinib/dasatinib combination chemotherapy. Further investigations are warranted to clarify the prognostic significance of IKZF1plus in adult Ph+ ALL patients.


Assuntos
Fator de Transcrição Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudos Prospectivos , Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mesilato de Imatinib/uso terapêutico , Dasatinibe/uso terapêutico , Prognóstico
3.
Am J Hematol ; 98(1): 102-111, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36260658

RESUMO

HCT recipients reportedly have a high mortality rate after developing COVID-19. SARS-CoV-2 vaccination is generally useful to prevent COVID-19. However, its safety and efficacy among HCT recipients remain elusive. This large-scale prospective observational study including 543 HCT recipients with 37-months interval from transplant demonstrated high safety profiles of mRNA vaccine: only 0.9% of patients avoided the second dose due to adverse event or GVHD aggravation following the first dose. Regarding the efficacy, serological response with a clinically relevant titer (≥250 BAU/mL) was obtained in 397 (73.1%) patients. We classified the remaining 146 patients as impaired responders and compared the clinical and immunological parameters between two groups. In allogeneic HCT recipients, multivariable analysis revealed the risk factors for impaired serological response as follows: age (≥60, 1 points), HLA-mismatched donor (1 points), use of systemic steroids (1 points), absolute lymphocyte counts (<1000/µL, 1 points), absolute B-cell counts (<100/µL, 1 points), and serum IgG level (<500 mg/dL, 2 points). Notably, the incidence of impaired serological response increased along with the risk scores: patients with 0, 1-3, and 4-7 points were 3.9%, 21.8%, and 74.6%, respectively. In autologous HCT recipients, a shorter interval from transplant to vaccination was the only risk factor for impaired serological response. Our findings indicate that two doses of SARS-CoV-2 vaccine are safe but insufficient for a part of HCT recipients with higher risk scores. To improve this situation, we should consider additional treatment options, including booster vaccination and prophylactic neutralizing antibodies during the SARS-CoV-2 pandemic.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , População do Leste Asiático , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , RNA Mensageiro , SARS-CoV-2 , Transplantados , Vacinação , Japão
4.
Transfus Apher Sci ; 60(6): 103279, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34563457

RESUMO

Plerixafor and bortezomib have recently been used in autologous stem cell collection to increase the amount of stem cells collected. However, no reports have described the combined use of plerixafor and bortezomib in cases of dialysis-dependent multiple myeloma. The dialysis-dependent multiple myeloma patient in the present study had a small amount of CD34-positive cells with plerixafor and filgrastim, and also with bortezomib and cyclophosphamide. However, by adding plerixafor to bortezomib and cyclophosphamide, collected CD34-positive cells were increased six-fold compared to the previous day. These findings suggest that the combination of plerixafor and bortezomib may be effective in those patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzilaminas/uso terapêutico , Ciclamos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Diálise Renal/métodos , Fármacos Anti-HIV/farmacologia , Benzilaminas/farmacologia , Ciclamos/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia
5.
Ann Hematol ; 98(11): 2579-2591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628517

RESUMO

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Infecções/epidemiologia , Infecções/etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Eur J Haematol ; 103(3): 164-171, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132205

RESUMO

OBJECTIVE: We investigated whether minimal residual disease (MRD) status in adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is useful for decision on clinical indications for allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. RESULTS: Among 103 adult ALL patients enrolled, 59 were Ph-negative, and MRD status was assessed in 51 patients. The probability of 3-year overall survival (OS) and disease-free survival (DFS) was 69% (95%CI 54-80) and 50% (95%CI 36-63), respectively. Patients who were MRD-negative after induction therapy (n = 15) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 30; 73% vs 41%, P = 0.018). Patients who were MRD-positive after induction but became MRD-negative after consolidation chemotherapy C in the first course (n = 11) showed a significantly worse 3-year DFS compared with patients who were MRD-negative after induction chemotherapy A in the first course (45% vs 73%, P = 0.025). CONCLUSIONS: These results indicate that DFS of about 70% can be expected in MRD-negative patients after induction therapy, and the patients did not benefit from HSCT in 1CR. This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000001519.


Assuntos
Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Idoso , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Prospectivos , Gestão da Segurança , Translocação Genética , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
7.
Rinsho Ketsueki ; 60(2): 118-123, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30842378

RESUMO

A 57-year-old man with high-risk myelodysplastic syndrome underwent umbilical cord blood transplantation. He began receiving steroids on day 14 for acute graft-versus-host disease, and experienced dizziness on day 75 during gradual dose reduction. Multiple hemorrhages were observed in the cerebrum, cerebellum, and brainstem. His bleeding increased, and he underwent a brain biopsy on day 91. Subsequently, he was diagnosed with central nervous system vasculitis (CNSV) on the basis of the observed aggregation of mature CD3+ lymphocytes around small vessels and vascular wall invasion by lymphocytes and macrophages. After receiving high-dose steroid therapy, cerebral hemorrhage stopped; however, dysphasia occurred on day 113 and the patient died of cerebral edema on day 128. Toxoplasma DNA and tachyzoites were detected in the brain biopsy specimen during additional examinations; therefore, we suspected that the toxoplasmosis was related to the onset of CNSV. CNSV is a rare, rapidly progressing disease that may present as a fatal post-transplantation central nervous system complication. Investigating the causes of CNSV, including CNSV associated with toxoplasmosis, is critically important for improving the prognosis of patients with CNSV.


Assuntos
Hemorragia Cerebral/diagnóstico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Toxoplasmose/diagnóstico , Vasculite do Sistema Nervoso Central/diagnóstico , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia
8.
Br J Haematol ; 177(4): 578-587, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28340283

RESUMO

Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dasatinibe/uso terapêutico , Ecocardiografia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/complicações , Masculino , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Resultado do Tratamento , Insuficiência da Valva Tricúspide/etiologia , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 22(9): 1608-1614, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27220263

RESUMO

Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.


Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Doença Enxerto-Hospedeiro/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo
11.
Chem Pharm Bull (Tokyo) ; 64(7): 838-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27373640

RESUMO

Thioglycosides are available donors in glycosylation due to the stability of the anomeric C-S bond under general reaction conditions of protection and deprotection, and offer orthogonality in their activation. We report now that the hypervalent iodine effectively induced glycosylation reaction of thioglycosides with various alcohols. This method features a high efficiency, completion in a short time, and proceeding under very mild conditions.


Assuntos
Iodo/química , Iodobenzenos/química , Tioglicosídeos/química , Ácido Trifluoracético/química , Álcoois/química , Glicosilação , Indicadores e Reagentes , Estrutura Molecular
12.
Rinsho Ketsueki ; 57(8): 1004-10, 2016 08.
Artigo em Japonês | MEDLINE | ID: mdl-27599416

RESUMO

We describe two hemodialysis patients with high-risk myelodysplastic syndrome (MDS) treated with azacitidine. A 65-year-old woman (case 1) received azacitidine at 75 mg/m(2) for 7 days, and a 52-year-old man (case 2) with liver cirrhosis received a 70% dose of azacitidine. Both cases developed grade 4 cytopenia, but they achieved transfusion independence after 3 and 2 courses, and the durations of remission were 10 and 11 months, respectively. Case 1 had the complication of febrile neutropenia (FN) twice during the 1(st) and 2(nd) courses, but continued to receive azacitidine treatment thereafter. Case 2 developed infectious peritonitis during the sixth course, and azacitidine treatment was thus discontinued. After a 4-month treatment interruption, he became transfusion-dependent, and re-induction of azacitidine was successful. Of note, the course of case 1 was complicated by erythema nodosum on admission, which then disappeared after one course of azacitidine treatment. The mean durations of hospitalization were 17.5 and 23 days per course of azacitidine treatment, respectively. Though there are few reports of azacitidine treatment for hemodialysis patients with high-risk MDS, we advocate administering azacitidine to such patients, while paying close attention to the dose intensity of azacitidine and taking prompt action to manage infectious complications.


Assuntos
Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Transfusão de Sangue , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Diálise Renal , Fatores de Risco
13.
Ann Hematol ; 94(7): 1159-65, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25704584

RESUMO

The introduction of reduced-intensity conditioning (RIC) regimens has made possible allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML). However, the optimal timing of allo-HCT in these patients and its relative risks and benefits when compared with chemotherapies have not been determined. This retrospective study by the Fukuoka Blood and Marrow Transplant Group compared RIC allo-HSCT with non-transplant therapies, the choice based on donor availability, in AML patients in their first complete remission (CR1). The prognostic value of various patient characteristics and disease-specific variables were investigated in 299 patients aged ≥60 years with AML in CR1. Among the 107 patients aged 60-65 years, 54 of whom received allo-HCT and 53 of whom continued chemotherapies; allo-HCT, adverse-risk group, and hematopoietic cell transplantation-comorbidity index were significant predictors of survival outcomes. Among 192 patients aged ≥66 years deemed ineligible for allo-HCT, relapse and Karnofsky performance status after induction therapy were significant predictors of survival outcomes. Findings from this study may facilitate a new standard of care for older AML patients in CR1 who are considered candidates for allo-HCT.


Assuntos
Análise Citogenética/métodos , Definição da Elegibilidade/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão/métodos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
14.
Chem Pharm Bull (Tokyo) ; 63(10): 819-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26423039

RESUMO

The facile and clean oxidative coupling reaction of pyrroles with azoles has been achieved using the recyclable hypervalent iodine(III) reagents having adamantane structures. These iodine(III) reagents could be recovered from the reaction mixtures by a simple solid-liquid separation, i.e., filtration, for reuse.


Assuntos
Azóis/síntese química , Iodo/química , Pirróis/síntese química , Adamantano/química , Azóis/química , Química Verde , Indicadores e Reagentes , Oxirredução , Pirróis/química
15.
Bone Marrow Transplant ; 59(4): 466-472, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38238452

RESUMO

The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Humanos , Prognóstico , Estudos Retrospectivos , Antígenos HLA , Antígenos de Histocompatibilidade , Antígenos HLA-B/genética , Recidiva , Alelos , Teste de Histocompatibilidade
16.
Intern Med ; 62(5): 689-695, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35871587

RESUMO

Objective The prognostic factors for azacitidine in untreated acute myeloid leukemia (AML) patients ineligible for intensive therapy remain unknown. To identify prognostic factors for azacitidine monotherapy and assist clinicians in deciding whether to use azacitidine monotherapy or other therapies. Methods We retrospectively analyzed 27 patients with AML who were newly treated with azacitidine between 2013 and 2021 at our hospital. We evaluated potential predictors based on the overall survival (OS). Results A univariate analysis found that an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and platelet count (Plt) <27,000/µL had a significant negative influence on the OS. A multivariate analysis confirmed that both factors had significant independent adverse effects on the OS. An ECOG PS ≥2 and Plt <27,000/µL were thus assigned 1 point each, and a clinical scoring system was created. Log-rank testing showed that the 0-point group (n=12) had a median OS of 680 days [95% confidence interval (CI) 220-898 days] and a 1-year OS rate of 80.8% (95% CI 42.3-94.9%), the 1-point group (n=11) had a median OS of 90 days (95% CI 62-345 days) and a 1-year OS rate of 18.2% (95% CI 2.9-44.2%), and the 2-point group (n=4) had a median OS of 82 days [95% CI 19-not applicable (NA) days] and a 1-year OS rate of 0% (95% CI NA-NA). The p value of 0.00008 indicated that this scoring was useful. Conclusion The ECOG PS and Plt can be used to predict the OS with azacitidine monotherapy in untreated AML patients ineligible for intensive therapy.


Assuntos
Azacitidina , Leucemia Mieloide Aguda , Humanos , Azacitidina/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
17.
EJHaem ; 4(3): 714-718, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37601868

RESUMO

We studied the pathophysiology of aplastic anaemia (AA) in six different pairs of relatives without a family history of hematologic disorders or congenital AA. Five and four of the six pairs shared the HLA-DRB1*15:01 and B*40:02 alleles, respectively. Glycosylphosphatidylinositol-anchored protein-deficient blood cells were detected in eight of the 10 patients evaluated. In a mother-daughter pair from one family, flow cytometry detected leukocytes lacking HLA-A2 due to loss of heterogeneity in chromosome 6p. Whole-exome sequencing of the family pair revealed a missense mutation in MYSM1. These results suggest that genetic inheritance of immune traits might underlie familial AA in some patients.

18.
Vaccine ; 41(47): 6899-6903, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37866994

RESUMO

This prospective observational study aimed to assess the serological response and safety after the third booster shot of SARS-CoV-2 mRNA vaccines in 292 hematopoietic cell transplant (HCT) recipients. In our patients, mild systemic reactions were present in 10-40% and GVHD aggravation in 1.1%. Overall, clinically relevant response (>250 U/mL) was observed in 93.1% of allogeneic (allo)-HCT recipients and 70.6% of autologous (auto)-HCT recipients, respectively. Of note, detectable antibody response with any titer following the first two doses was a powerful predictor for adequate response after booster shot in both cohorts. For such patients, 98.8% of allo- and 92.3% of auto-HCT recipients obtained clinically relevant response after dose 3. In addition, continued systemic steroid and/or calcineurin inhibitors at the booster shot significantly correlated with serological response. These findings highlighted that booster vaccination efficiently improved serological response without safety concerns and thus recommended for the majority of HCT recipients.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , População do Leste Asiático , Transplantados , Vacinas contra COVID-19/administração & dosagem
20.
J Med Case Rep ; 16(1): 311, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35978379

RESUMO

BACKGROUND: Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients. CASE PRESENTATION: A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared. CONCLUSIONS: Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.


Assuntos
Doenças do Sistema Endócrino , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Polineuropatias , Adulto , Anticorpos Monoclonais , Dexametasona/uso terapêutico , Feminino , Filgrastim , Mobilização de Células-Tronco Hematopoéticas , Humanos , Lenalidomida , Polineuropatias/tratamento farmacológico , Transplante Autólogo
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