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Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.
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BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454â419â days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), Pâ=â0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, Pâ<â0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, Pâ=â0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all Pâ<â0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Análisis de Series de Tiempo Interrumpido , Humanos , Estudios Longitudinales , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Farmacorresistencia Bacteriana , Leucemia/tratamiento farmacológico , Leucemia/complicaciones , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/normasRESUMEN
In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Humanos , Acondicionamiento Pretrasplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adulto , Neoplasia Residual , Trasplante Homólogo/métodos , Anciano , Adolescente , Adulto Joven , Agonistas Mieloablativos/uso terapéutico , AloinjertosRESUMEN
Acute lymphoblastic leukemia (ALL) is one of the most rapidly changing hematological malignancies with advanced understanding of the genetic landscape, detection methods of minimal residual disease (MRD), and the development of immunotherapeutic agents with good clinical outcomes. The annual incidence of adult ALL in Korea is 300-350 patients per year. The WHO classification of ALL was revised in 2022 to reflect the molecular cytogenetic features and suggest new adverse- risk subgroups, such as Ph-like ALL and ETP-ALL. We continue to use traditional adverse-risk features and cytogenetics, with MRD-directed post-remission therapy including allogeneic hematopoietic cell transplantation. However, with the introduction of novel agents, such as ponatinib, blinatumomab, and inotuzumab ozogamicin incorporated into frontline therapy, good MRD responses have been achieved, and overall survival outcomes are improving. Accordingly, some clinical trials have suggested a possible era of chemotherapy-free or transplantation-free approaches in the near future. Nevertheless, relapse of refractory ALL still occurs, and some poor ALL subtypes, such as Ph-like ALL and ETP-ALL, are unsolved problems for which novel agents and treatment strategies are needed. In this review, we summarize the currently applied diagnostic and therapeutic practices in the era of advanced genetic analysis and targeted immunotherapies in United States and Europe and introduce real-world Korean data.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inducción de Remisión , RecurrenciaRESUMEN
Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.
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BACKGROUND: The association between leukapheresis (LK) as a treatment option for hyperleukocytosis (HL) in patients with acute myeloid leukemia (AML) remains controversial. METHODS: Data were extracted from the electronic medical record for 2801 patients with AML between April 2009 and December 2019. LK was performed when the leukocyte count was ≥100 × 109 /L at the time initial bone marrow examination. RESULTS: A comparison between the patients with HL in the non-LK (n = 1579) and LK (n = 208) groups revealed survival probabilities (%) of 93.2% and 90.4% (P = .130) for day 30 (D30), 85.4% and 84.2% (P = .196) for D60, and 83.6% and 80.8% (P = .258) for D90, respectively. After propensity score matching, a comparison between the patients with HL in the non-LK (n = 192) and LK (n = 192) groups revealed survival probabilities (%) of 83.9% and 91.2% (P = .030) for D30, 75.0% and 84.9% (P = .015) for day 60 (D60), and 62.4% and 81.3% (P = .034) for day 90 (D90), respectively. After D150, the observed effect of LK appeared to be mitigated without a survival benefit. DISCUSSION: LK was associated with improved early survival outcomes at D30, D60, and D90 among patients with AML exhibiting HL. Thus, it may be considered a treatment option for reducing cell mass in such patients.
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Leucemia Mieloide Aguda , Leucocitosis , Humanos , Estudios de Cohortes , Leucocitosis/terapia , Leucaféresis , Puntaje de Propensión , Leucemia Mieloide Aguda/terapiaRESUMEN
To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia/terapia , Linfoma no Hodgkin/terapia , Linfoma de Células B Grandes Difuso/terapia , Estudios RetrospectivosRESUMEN
Acute myeloid leukemia (AML) is a clinical emergency requiring treatment and results in high 30-day (D30) mortality. In this study, the prediction of D30 survival was studied using a machine learning (ML) method. The total cohort consisted of 1700 survivors and 130 non-survivors at D30. Eight clinical and 42 laboratory variables were collected at the time of diagnosis by pathology. Among them, six variables were selected by a feature selection method: induction chemotherapy (CTx), hemorrhage, infection, C-reactive protein, blood urea nitrogen, and lactate dehydrogenase. Clinical and laboratory data were entered into the training model for D30 survival prediction, followed by testing. Among the tested ML algorithms, the decision tree (DT) algorithm showed higher accuracy, the highest sensitivity, and specificity values (95% CI) of 90.6% (0.918-0.951), 70.4% (0.885-0.924), and 92.1% (0.885-0.924), respectively. DT classified patients into eight specific groups with distinct features. Group 1 with CTx showed a favorable outcome with a survival rate of 97.8% (1469/1502). Group 6, with hemorrhage and the lowest fibrinogen level at diagnosis, showed the worst survival rate of 45.5% (25/55) and 20.5 days. Prediction of D30 survival among AML patients by classification of patients with DT showed distinct features that might support clinical decision-making.
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BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.
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Bronquiolitis Obliterante , Trasplante de Células Madre Hematopoyéticas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Bromuro de Tiotropio/uso terapéutico , Budesonida/uso terapéutico , Estudios Retrospectivos , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/etiología , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , BroncodilatadoresRESUMEN
BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Trasplante Autólogo , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Antígenos CD34 , Moléculas de Adhesión Celular , RecurrenciaRESUMEN
Background: Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Objectives: We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. Design: We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Methods: Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy (n = 113) or blinatumomab, which was available since late 2016 (n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score-matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Results: Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p < 0.001). Among the CR patients with available minimal residual disease (MRD) results, 68.6% in blinatumomab group and 40.0% in conventional chemotherapy group were MRD-negative. Regimen-related mortality during the chemotherapy cycles was significantly higher in the conventional chemotherapy group (40.4% versus 1.9%, p < 0.001). Estimated 3-year overall survival (OS) was 33.2% (median, 26.3 months) after blinatumomab, and 15.4% (median, 8.2 months) after conventional chemotherapy (p < 0.001). Estimated 3-year non-relapse mortality were 30.3% and 51.9% (p = 0.004), respectively. In multivariate analysis, CR duration < 12 months showed more relapses and poor OS, and conventional chemotherapy showed higher non-relapse mortality and poor OS. Conclusions: Matched cohort analysis showed superior outcomes of blinatumomab compared with conventional chemotherapy. However, large numbers of relapses and non-relapse mortalities continue to occur even after blinatumomab followed by allo-HCT. Novel therapeutic strategies are still needed for R/R BCP-ALL.
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Recently, the combination of VEN-HMA has been shown to achieve durable responses in patients with both newly diagnosed (ND) and R/R-AML. We retrospectively evaluated the post-allo-HCT outcomes of 50 patients who received VEN-HMA therapy. In total, 10 were ND and 40 were R/R and, at the time of HCT, the median age was 53 years. In the ND- and R/R-AML groups, the percentage of patients who achieved CR/CRi or MLFS was 90% and 92.5%, respectively. In all, after a median follow-up of 13.7 months, the probabilities of overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. In addition, the cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and moderate-severe chronic GVHD at 1 year were 28.4% and 37.4%, respectively. In multivariate analysis, the factors associated with a statistically significant impact on OS were VEN-HMA cycle (p = 0.021), ELN risk group (p = 0.041), and the response to VEN-HMA therapy before allo-HCT (p = 0.003). Although 80% of our patients had R/R-AML and 30% underwent a second allo-HCT, our data still suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option.
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BACKGROUND: In acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis (HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety. METHODS: We retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 109/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared. RESULTS: There was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval [CI], 77.8%-100.0%) versus 58.3% (95% CI, 38.6%-78.1%) (P = 0.03) in "sequential HL" and 76.7% (95% CI, 61.5%-91.8%) versus 54.8% (95% CI, 37.3%-72.4%) (P = 0.03) in "symptomatic HL," respectively. Moreover, in the "sequential HL" subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group. CONCLUSIONS: In APL with "sequential HL" or "symptomatic HL" from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.
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Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Estudios Retrospectivos , Leucocitosis/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tretinoina/efectos adversosRESUMEN
There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 adult AML patients who received SCT2 from haploidentical donors (HIT, N = 32) and double-cord blood (dCBT, N = 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow WT1 measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that WT1-MRD negativity may be warranted for better SCT2 outcomes.
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Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently identified high-risk subgroup of T-cell ALL in children. However, there have been conflicting reports and limited data have been reported in adult patients. We retrospectively analyzed the cytogenetic and molecular characteristics and long-term survival outcomes of adult patients with ETP-ALL versus non-ETP-ALL. We analyzed 58 patients (median age, 35 years [range, 18-76 years]) with newly diagnosed T-cell ALL who received a uniform remission induction and consolidation chemotherapy with suitable samples for genetic analyses. If a donor was available, all patients were recommended allogeneic hematopoietic cell transplantation (allo-HCT) for post-remission therapy. Out of 58 patients, 21 (36.2%) had ETP-ALL. Patients with ETP-ALL were older and had a higher proportion of complex karyotype than non-ETP-ALL. Additionally, more DNMT3A mutations were detected in ETP-ALL, whereas FBXW7 mutations and CDKN2A/CDKN2B deletions were found nearly exclusively in non-ETP-ALL. The overall complete remission (CR) rates were not different between ETP-ALL (95.2%) and non-ETP-ALL (81.1%) and subsequent allo-HCT proceeding rates in CR1 were 61.9% for ETP-ALL and 43.2% for non-ETP-ALL, respectively. The overall prognosis of patients with T-ALL was poor that estimated 5-year overall survival (OS) was 33.3% for ETP-ALL and 29.5% for non-ETP-ALL. In a subgroup analysis of patients treated with allo-HCT in CR1 (n = 29), 5-year OS was 53.8% for ETP-ALL and 55.4% for non-ETP-ALL. Our data showed molecular characteristics of ETP-ALL and non-ETP-ALL and revealed that intensive chemotherapy followed by allo-HCT for post-remission therapy can contribute to preserved survival outcome of adult patients with ETP-ALL.
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Trasplante de Células Madre Hematopoyéticas , Células Precursoras de Linfocitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Niño , Humanos , Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Estudios Retrospectivos , Pronóstico , Inducción de Remisión , Análisis CitogenéticoRESUMEN
Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p < 0.01). The 30-day (2.7% vs. 9.5%, p = 0.17) and 60-day (9.5% vs. 18.9%, p = 0.16) mortality rates did not differ between the two groups, nor did the median hospitalization and transfusion rates (hospitalization: 23 days vs. 21 days, p = 0.20; red blood cells: 3.2 units/month vs. 3.5 units/month, p = 0.73; platelets: 2.7 units/month vs. 2.3 units/months, p = 0.48). Of those who received DEC + VEN and became leukemia-free, 29% underwent allogeneic stem cell transplantation and had excellent survival outcomes (one-year survival: 79.4%; one-year non-relapse mortality: 13.3%). This study is the first to provide real-world evidence that DEC + VEN has superior outcomes to DEC monotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Humanos , Anciano , Decitabina/uso terapéutico , Puntaje de Propensión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Azacitidina/uso terapéuticoRESUMEN
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are divided in three major groups: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 WHO classification incorporates also prefibrotic PMF (pre-PMF) and overt PMF. This study aimed to discriminate the clinical features, genetic alterations, and outcomes in patients with prefibrotic, overt PMF, and secondary MF (SMF). This study included 229 patients with diagnosed myelofibrosis (MF). Among 229 patients, 67 (29%), 122 (53%), and 40 (18%) were confirmed as SMF, overt PMF, and pre-PMF, respectively. The JAK2 V617F mutation was differentially distributed in SMF and PMF, contradictory to CALR and MPL mutations. Regarding nondriver mutations, the occurrence of ASXL1 mutations differed between PMF and SMF or pre-PMF. The three-year overall survival was 91.5%, 85.3%, and 94.8% in SMF, overt PMF, and pre-PMF groups. Various scoring systems could discriminate the overall survival in PMF but not in SMF and pre-PMF. Still, clinical features including anemia and thrombocytopenia were poor prognostic factors throughout the myelofibrosis, whereas mutations contributed differently. Molecular grouping by wild-type SF3B1 and SRSF2/RUNX1/U2AF1/ASXL1/TP53 mutations showed inferior progression-free survival (PFS) in PMF, SMF, and pre-PMF. We determined the clinical and genetic features related to poor prognosis in myelofibrosis.
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BACKGROUND: Granulocyte transfusions (GTs) have been used to treat infections in neutropenic patients undergoing chemotherapy or hematopoietic stem cell transplantation. However, there is persistent controversy regarding their outcomes. We aimed to analyze accumulated clinical and laboratory data from patients with acute myeloid leukemia (AML) who underwent GT at our institution in the last 10 years to determine optimal parameters to estimate the GT effect. We hypothesized that patients grouped according to prognostic factors would have inconsistent clinical outcomes. MATERIALS AND METHODS: In this single-center retrospective study, we collected medical records of 219 GT-treated patients diagnosed with AML from 2009 to 2019. Prognostic factors, including clinical and laboratory parameters, were assessed. Serial measurements of laboratory parameters before and after GT were collected, and the area under the curve of the white blood cells (AUC-WBC) was calculated using the trapezoidal method. A prognostic scoring system using 8 factors from multivariate analysis was analyzed. The primary outcome was survival at 30 days (D30) after GT initiation. RESULTS: The 8 factors for the prognosis scoring system included secondary AML, mean AUC-WBC, prothrombin time, and levels of blood urea nitrogen (BUN), bilirubin, alanine aminotransferase (ALT), phosphorus, and lactate dehydrogenase (LDH). Patients were grouped into 4 risk groups (low, medium, high, and very high), and the D30 survival rates for each group were as follows: 87.6% (99/113), 55.9% (33/59), 21.1% (4/19), and 0% (0/19), respectively. Hematopoiesis, liver, and renal function affected the outcome. FLT3 mutation acted as a favorable factor for D30 survival. CONCLUSIONS: GT response in patients with AML seemed to be reflected by 8 score markers, and GT was significantly effective in the low-risk group. We suggest that it is important to evaluate the risk assessment of patients before GT to achieve better outcomes.