RESUMO
To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4â¯% vs. 14â¯% at five years post-transplant, respectively, p = 0.26; OS: 81â¯% vs. 66â¯%, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.
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A prospective multicenter observational study of organ response was conducted in patients with chronic GVHD diagnosed by the NIH criteria. When response was assessed at 12 months (12 M) in 118 patients, 74.6% were classified as responders and 25.4% as non-responders. The skin and oral cavity were the most frequent organs used as the basis for determining overall response. The lungs, liver, and eyes were also used in 20% of patients. Non-response decisions at 12 M were most frequent in the lungs. A significantly higher percentage of responders than non-responders completed systemic treatment (24.3% vs. 3.3%, P = 0.02). Global scoring showed significant changes, with improvement in responders and worsening in non-responders throughout the observation period. Two-year transplant-related mortality, using the 12 M assessment as the landmark, was significantly worse in non-responders (28.5% vs. 2,7%, P = 0.0001), while the 2-year recurrence rate was equivalent (5.4% vs. 4.8%, P = 0.78). Consequently, the 2-year overall survival rate from the 12 M assessment was significantly better in responders than non-responders (95% vs. 65.3%, P = 0.0001). Our data suggests that patients who do not achieve a response within the first year should be candidates for clinical studies on chronic GVHD.
Assuntos
Doença Enxerto-Hospedeiro , Humanos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Estudos Prospectivos , Doença Crônica , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Japão/epidemiologia , Idoso , Taxa de Sobrevida , Transplante de Células-Tronco Hematopoéticas , Resultado do Tratamento , Adolescente , Adulto Jovem , Fatores de Tempo , População do Leste AsiáticoRESUMO
The outcomes of relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant to new drugs such as tyrosine kinase inhibitors, inotuzumab ozogamicin (InO) and blinatumomab are dismal. We treated two cases of Ph+ALL resistant to these drugs that achieved long-term survival after treatment with chimeric antigen receptor (CAR)-T cell therapy or a second allogeneic hematopoietic stem cell transplantation (HCT) with a sequential conditioning regimen. Case 1: A 15-year-old boy was diagnosed with Ph+ALL. Despite the second HCT after the treatment of ponatinib and blinatumomab, hematological relapse occurred. InO was ineffective and he was transferred to a CAR-T center. After the CAR-T cell therapy, negative measurable residual disease (MRD) was achieved and maintained for 38 months without maintenance therapy. Case 2: A 21-year-old man was diagnosed with Ph+ALL. Hematological relapse occurred after the first HCT. Despite of the treatment with InO, ponatinib, and blinatumomab, hematological remission was not achieved. The second HCT was performed using a sequential conditioning regimen with clofarabine. Negative MRD was subsequently achieved and maintained for 42 months without maintenance therapy. These strategies are suggestive and helpful to treat Ph+ALL resistant to multiple immunotherapies.
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Transplante de Células-Tronco Hematopoéticas , Imidazóis , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Piridazinas , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Piridazinas/uso terapêutico , Adolescente , Imidazóis/uso terapêutico , Adulto Jovem , Imunoterapia , Recidiva , Transplante HomólogoAssuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Recidiva , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos Quiméricos/imunologiaRESUMO
Measurable residual disease (MRD)-guided pre-emptive therapies are now widely used to prevent post-transplant hematological relapse in patients with acute myeloid leukemia (AML). This single-center retrospective study aimed to clarify the significance of pre-emptive treatment based on Wilms' tumor gene-1 mRNA (WT1) monitoring for MRD in patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with AML who received chemotherapy for hematological relapse or WT1 increase after allo-HSCT were eligible for inclusion. From January 2017 to June 2022, 30 patients with a median age of 57 (16-70) years were included and stratified into two groups: 10 with WT1 increase and 20 with hematological relapse. The median times from HCT to WT1 increase or hematological relapse were 309 days (range: 48-985) or 242 days (range: 67-1116), respectively. Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year overall survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P = 0.024) and 70% vs. 29% (P = 0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in patients with AML who have undergone allo-HSCT.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasia Residual , Transplante Homólogo , Proteínas WT1 , Humanos , Leucemia Mieloide Aguda/terapia , Adulto , Pessoa de Meia-Idade , Proteínas WT1/genética , Feminino , Masculino , Idoso , Estudos Retrospectivos , Adolescente , Adulto JovemRESUMO
BACKGROUND: Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. OBJECTIVE: The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. STUDY DESIGN: A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. RESULTS: A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30-5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14-6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. CONCLUSION: The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further investigations are needed to validate the novel markers, analysis of the pathophysiology, and application to treatment settings other than HCT.
Assuntos
Biomarcadores , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Adulto , Biomarcadores/sangue , Pessoa de Meia-Idade , Transplante Homólogo/métodos , Estudos Prospectivos , Prognóstico , Condicionamento Pré-Transplante/métodos , Proteína C-Reativa/metabolismo , Idoso , Adulto Jovem , Adolescente , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Resultado do TratamentoRESUMO
A 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, who had a 5/8 HLA haploidentical match. However, the patient had donor-specific antibodies against the donor's HLA-B 0702 and HLA-C 0702. To address this issue, after rituximab therapy, the patient was given platelet transfusions from B0702- and C0702-positive donors on day - 1 and day 0, and immunoglobulin on day 0, followed by PBSCT. Donor-specific antibodies decreased by over 90%, and engraftment was confirmed on day 13. Since then, the patient has remained relapse-free and healthy. This case suggests that appropriate management of donor-specific antibodies can enable safe transplantation, even in donors who test positive for these antibodies.
Assuntos
Antígenos HLA , Humanos , Feminino , Adulto , Antígenos HLA/imunologia , Dessensibilização Imunológica/métodos , Doadores de Tecidos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Haploidêntico , Isoanticorpos/imunologia , Isoanticorpos/sangue , Transplante de Células-Tronco de Sangue Periférico , Transfusão de PlaquetasRESUMO
There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.
Assuntos
Proteína C-Reativa , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Inflamação , Estado Nutricional , Idoso , Humanos , Biomarcadores , Proteína C-Reativa/análise , Proteína C-Reativa/química , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Albumina Sérica/análise , Albumina Sérica/química , Inflamação/diagnósticoRESUMO
The CFA ratio, calculated using pretreatment C-reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15-75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable-risk group, 197 patients (60.1%) in the intermediate-risk group, and 58 patients (17.7%) in the adverse-risk group. The median CFA ratio was 1.07 (0-67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow-up of 91.2 months, the 7-year overall survival (OS) and disease-free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7-year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7-year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML.
Assuntos
Leucemia Mieloide Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminas , Fibrinogênio , Prognóstico , Estudos Retrospectivos , Adolescente , Adulto Jovem , IdosoRESUMO
Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Masculino , Transplante de Células-Tronco Hematopoéticas/métodos , Prognóstico , Cariótipo Anormal , Fatores de Risco , Estudos RetrospectivosRESUMO
The clinical implications of recipient bone marrow nucleated cell count (NCC) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unknown. We conducted a multicenter retrospective study to evaluate the clinical significance of bone marrow NCC prior to allo-HSCT in patients with acute lymphoblastic leukemia. Patients who were in remission and underwent the initial allo-HSCT were included and stratified into high- and low-NCC groups using an NCC of 10 × 104/µL as the cut-off. The 3-year overall survival (OS), non-relapse mortality (NRM), and relapse rates for the high- and low-NCC groups were 51.2 vs. 84.5% (p < 0.001), 27.5 vs. 6.5% (p < 0.001), and 31.1 vs. 24.4% (p = 0.322), respectively. The high-NCC group had significantly poorer OS and higher NRM when compared with the low-NCC group. In summary, high recipient bone marrow NCC is associated with higher NRM and lower OS following allo-HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Medula Óssea , Estudos Retrospectivos , Relevância Clínica , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , RecidivaRESUMO
Primary vitreoretinal lymphoma (PVRL) is a rare subtype of malignant lymphoma with a poor prognosis because of high frequency of central nervous system (CNS) progression. Identification of factors associated with CNS progression is essential to improve the prognosis of patients with PVRL. We conducted a retrospective study of 54 patients diagnosed with PVRL and treated at our hospital to identify factors associated with CNS progression and prognosis. All patients were treated with intravitreal methotrexate (MTX) injections in the affected eyes until lesion resolution. Twenty-four patients were treated with systemic administration of high-dose MTX (systemic HD-MTX) every other week for a total of five cycles following intravitreal MTX injection. Of 24 patients, 20 completed five cycles of systemic HD-MTX. The 5-year cumulative incidence of CNS progression and overall survival (OS) rate were 78.0% and 69.0% respectively. By univariate and multivariate analyses, bilateral disease and the detection of B-cell clonality confirmed by flow cytometric analysis were risk factors associated with CNS progression. Moreover, systemic HD-MTX completion reduced the risk of CNS progression and was identified as a factor affecting OS. In this study, factors for CNS progression identified may potentially contribute to the optimized therapeutic stratification to improve the survival of patients with PVRL.
Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Neoplasias da Retina , Humanos , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/patologia , Estudos Retrospectivos , Corpo Vítreo/patologia , Linfoma/tratamento farmacológico , Sistema Nervoso Central/patologia , MetotrexatoRESUMO
The optimal bridge strategy at the decision for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndrome (MDS) is unclear. We performed a prospective observational study in which 110 patients with MDS who were decided to undergo HSCT were enrolled. Among these 110 patients, 77 patients were enrolled in this study within 1 month from the decision for HSCT. Among these 77 patients, 13 patients had a human leukocyte antigen (HLA)-matched sibling, 54 patients started an unrelated donor search, and the other 10 patients directly selected cord blood (CB) at the decision for HSCT, and 13 (100%), 38 (70.4%), and 9 (90%) patients actually underwent HSCT within 1 year, respectively. The overall survival (OS) at 1 year from their enrollment was 70.9%, and the selection of azacitidine use at the decision for HSCT was not associated with OS. Among 60 of the 77 patients who actually underwent HSCT within a year from their enrollment, a lower relapse rate after HSCT was observed in those who selected CB at the decision to undergo HSCT. However, this preferable effect of CB selection disappeared when patients who were enrolled in this study in > 1 month from the decision for HSCT were additionally included in the analyses. In conclusion, the selection of bridge strategy at the decision for HSCT did not affect outcomes in patients with MDS. The immediate performance of HSCT may be associated with better outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Azacitidina/uso terapêutico , Estudos Prospectivos , Transplante Homólogo , Estudos RetrospectivosRESUMO
OBJECTIVES AND METHODS: This single-center retrospective study was performed to evaluate the safety and efficacy of FMS-like tyrosine kinase 3 (FLT3) inhibitors before and after allogeneic hematopoietic cell transplantation (HCT) in relapsed/refractory patients with FLT3-mutation positive acute myeloid leukemia (AML). RESULTS: Ten patients who met the eligibility criteria were included. Eight of them achieved hematological remission at HCT, within a median span of 79 days (range: 43-197). In post-HCT, patients started maintenance therapy (MT; median time-to-start 79 days, range: 43-197), and the median duration of MT was 390 days (range: 67-815). Grade 3 hematological adverse events (AEs) were found in two patients, and non-hematological AEs were found in five patients. Nine patients underwent either dose reduction, discontinuation of therapy, or a switch to another FLT3 inhibitor due to AEs. Disease relapse occurred in one patient during MT. At the time of the last follow-up, seven patients are alive and disease-free, while three have died due to infection or transplant complications. CONCLUSION: In relapsed/refractory FLT3 mutation-positive AML, the use of FLT3 inhibitors can lead to high response rates and provide a safe bridge from HCT to MT. If sufficient attention is paid to safety, this therapy is expected to prevent disease relapse even with reduced dosages.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Compostos de Fenilureia/uso terapêutico , Estudos Retrospectivos , Recidiva , Mutação , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
The analysis of 165 children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia showed disease status at hematopoietic stem cell transplantation was a strong prognostic factor and clearly separated the patient outcomes.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Criança , Adolescente , Adulto Jovem , Transplante Homólogo , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapiaAssuntos
Inibidores da Dipeptidil Peptidase IV , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Incidência , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Dipeptidil Peptidases e Tripeptidil PeptidasesRESUMO
This 3+3 dose-escalation phase I multicenter study investigated the optimal dose of azacitidine (AZA) for post-hematopoietic stem cell transplantation (HSCT) maintenance, which remains unknown in Japan. Recipients of a first HSCT for high-risk myelodysplastic syndromes (MDS, n = 12) or acute myeloid leukemia (AML) with antecedent MDS (n = 3) received post-HSCT AZA maintenance in 2015-2019. The optimal AZA dose was defined as the dose at which 50-70% of patients can complete four cycles without dose-limiting toxicity (DLT). The initial dose level 1 was set as 30 mg/m2 for 5 days per 28-day cycle, and dose levels 0, 2, and 3 were set as 20, 40, and 50 mg/m2. DLT was defined as any grade 3 non-hematological or grade 4 hematological toxicity. The 15 evaluable patients were 55 (37-64) years old. The median observation of the post-HSCT survivors was 935 (493-1915) days. The median number of days post-HSCT to the start of AZA was 101 (59-176). In the first, second, and third cohorts, five of nine patients completed four cycles at dose level 1. In the final cohort, five of six additional patients completed at the same dose. In total, 10 (67%) patients tolerated AZA 30 mg/m2, which was determined as optimal. DLT occurred in five cases: grade 3 hepatotoxicity, pneumonia, enterocolitis, and grade 4 thrombocytopenia and neutropenia. The 2-year overall survival and disease-free survival rates post-HSCT were 77.0% and 73.3%. Post-HSCT AZA maintenance was well-tolerated and merits further evaluation for patients with MDS or AML with antecedent MDS. Trial registration: UMIN000018791.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Adulto , Pessoa de Meia-Idade , Azacitidina/efeitos adversos , Estudos Prospectivos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Chromosomal abnormalities in the role of prognostic factor for transplant patients with myelofibrosis (MF) are not fully investigated. Regarding complex karyotype (CK), we retrospectively analyzed 241 patients with primary and secondary MF who received a first allogeneic hematopoietic cell transplantation (HCT). Based on an unfavorable karyotype in the Dynamic International Prognostic Scoring System, we compared the outcomes in 3 groups: favorable karyotype, unfavorable karyotype including CK (unfavorable-CK(+)), and unfavorable karyotype not including CK (unfavorable-CK(-)). Overall survival was significantly shorter in the unfavorable-CK(+) group (hazard ratio (HR) 2.49, 95% CI: 1.46-4.24, P < 0.001), whereas there was no difference between the unfavorable-CK(-) group and the favorable group (HR 0.57, 95% CI: 0.20-1.59, P = 0.28). In addition, a significantly higher proportion of patients in the unfavorable-CK(+) group did not achieve complete remission after HCT (P = 0.007). The cumulative incidence of disease progression was significantly higher in the unfavorable-CK(+) group (HR 2.5, 95% CI 1.6-3.92, P < 0.001), whereas that in the unfavorable-CK(-) group was comparable to that in the favorable group (HR 0.49, 95% CI 0.12-1.94, P = 0.31). Further investigations will be needed to clarify the impact of CK on transplant outcomes in MF.
Assuntos
Prognóstico , Humanos , Estudos RetrospectivosRESUMO
Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment for myelodysplastic syndromes (MDS), although predicting post-transplant outcomes remains inconclusive. This study evaluated patients who underwent allo-HCT for MDS to identify prognostic factors and develop a clinical risk model.Methods: We evaluated 55 patients between June 2000 and March 2015 to identify prognostic factors and develop a model for three-year overall survival (OS) and event-free survival (EFS). Cox regression analysis was performed on four factors: age ≥55 years; Hematopoietic Cell Transplant-Comorbidity Index >2; intermediate or worse cytogenetic status based on revised International Prognostic Scoring System; and unrelated donor status associated with poor OS in the univariate analysis. A clinical risk model was constructed using the sum of the regression coefficients and evaluated using receiver operating characteristic analysis and five-fold cross-validation.Results: Patient median age was 51 (range: 30-67) years. Median follow-up was 45.8 (range: 1.27-193) months; the three-year OS and EFS rates were 61.8% and 56.4%, respectively. The areas under the curves (AUCs) for OS and EFS were 0.738 and 0.778, respectively, and the average AUC for 50 times five-fold cross-validation were 0.711 and 0.723 for three-year OS and EFS, respectively.Conclusion: A four-clinical-risk-factor model that could effectively predict post-transplantation outcomes and help decision-making in MDS treatment was developed.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplante HomólogoRESUMO
Outcomes in patients with acute lymphoblastic leukemia (ALL) who experience relapse after allogeneic hematopoietic cell transplantation (HCT) are unsatisfactory. This study aimed to evaluate the outcomes of patients with ALL who underwent second HCT (HCT2) for relapse after first HCT. It was a single-center retrospective study including adult patients with ALL who underwent HCT2 between 1991 and 2020. The cohort was stratified according to the transplant year, and included 39 patients with a median age of 29 years. A more recent transplant year was associated with achievement of complete remission (CR) and use of reduced-intensity conditioning (RIC), compared with an earlier transplant year. The overall survival (OS) rate and 2-year cumulative incidence of non-relapse mortality (recent vs. earlier) were 55% vs. 8% (P < 0.001) and 26% vs. 75% (P < 0.001), respectively. In multivariate analysis, non-CR (vs. CR; HR 3.6, 95% CI 1.2-11.3, P = 0.025) and myeloablative conditioning (vs. RIC; HR 3.5, 95% CI 1.3-9.4, P = 0.011) were negative prognostic factors for OS. Outcomes of the recent cohort from real-world data are promising, and achieving CR and using the RIC regimen at HCT2 may be an important therapeutic strategy.