scholarly journals Assessing Early Mortality in Intensively-Treated Acute Myeloid Leukemia in a Developing Country: Genetic, Laboratory Findings, and Comorbidities Add Prognostic Information

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Fernanda Rodrigues Mendes ◽  
Wellington F Silva ◽  
Raphael Bandeira Melo ◽  
Douglas R. A. Silveira ◽  
Elvira Velloso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Genetic Risk ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Newly Diagnosed ◽  
Laboratory Findings ◽  
Tumor Lysis ◽  
Acute Myeloid

Background: Early death (ED) during first-line therapy for acute myeloid leukemia (AML) is acknowledged as a pending issue worldwide. Few pivotal studies from developed countries have identified baseline characteristics related to poor outcome. Retrospective reports from Brazil and Mexico indicate alarming ED rates from real-world data, raising the question of which factors contribute towards this finding in low-income centers. In this study, we aimed to identify risk factors for ED in AML to increase the prediction power of previously known tools such as Charlson's Comorbidity Index (CCI) as well as to examine the role of anti-infective prophylaxis in our cohort. Methods: This is a retrospective cohort study involving adult patients (pts) newly diagnosed with AML treated at Instituto do Cancer do Estado de Sao Paulo, Brazil between June 2011 and June 2020. Only pts receiving the classic "7+3" regimen were included. We used a slight modification of European LeukemiaNet 2010 classification previously published by our group - Adapted Genetic Risk (AGR) (Silveira et al., 2020). The primary endpoint was ED rate, calculated by the Kaplan-Meier method. A Cox regression model selected by a stepwise method was used to find risk factors. Post-chemotherapy events (secondary endpoints) constituted any documented infection, bleeding, thrombosis, and acute kidney injury (AKI) during the first 30 days. Results: Overall, 206 out of 337 pts (61%) entered in the analysis. The median age was 54 years (range,17-74) and 50.5% were male. The median time between symptoms' onset and hospital admission was 7 weeks (0-48). Thirteen pts (6.3%) presented with leukostasis, of which 9 proceeded leukapheresis. At the presentation, clinical tumor lysis syndrome was seen in 12% of patients (associated with extramedullary disease [p<0.001], among other factors). Other baselines clinical and laboratory findings are summarized in table 1. Pre-chemotherapy infection was found in 67% of patients (positive blood culture: 26.3%). 45-day mortality was 23.8% (95% CI 17.8-29.4) (Figure 1), being 39.8% in pts above 60y. Dose reductions for liver or kidney dysfunction were not, per si, associated with higher ED. Multivariable Cox regression models examined the utility of baseline markers in predicting ED in our cohort and the best-fitted model by Akaike information criteria (AIC) is outlined in a forestplot (Figure 2). Briefly, in a model controlled for age, adding phenotype, genetic risk, platelets and C-reactive protein (CRP) to CCI resulted in improved prediction in our cohort (AIC 479 vs 542). CRP, AGR, and CCI were independently associated with short-term survival in AML (figure 3, 4, and 5). Noticeably, 13/20 diabetic patients died during the first 45 days (unadjusted HR 4.29 [95% CI 2.33-7.92]). Only antibacterial prophylaxis with quinolone was associated with decreased ED (unadjusted HR 0.38 [95% CI 0.15-0.95]), while the use of fluconazole or anidulafungin did not affect survival. Colonization during hospitalization occurred in 71% (mainly vancomycin-resistant Enterococcus [77%] and carbapenemase-producing Enterobacteriaceae [44%]). Any sort of colonization was associated with ED (OR 4.41 [95% CI 1.89-12.08]). Thromboembolic events were registered in 11.9% (95% CI 7.9-17.4, mostly catheter-related) and were marginally associated with central nervous system disease (OR 4.31 [95% CI 0.84-18.25) and diabetes mellitus (DM) (OR 3.24 [95% CI 0.94-9.82) 20.8 vs 7.9%, p=0.097). Bleeding was observed in 17.6% and was associated with monocytic AML subtypes, tumor lysis, and DM. Complete response was attained in 50.5% (95% CI 43.4- 57.5). Presumed or confirmed invasive fungal infection was diagnosed during induction in 26.6%, but empirical amphotericin was prescribed in 60.2%. 66.5% of subjects developed any grade of AKI, with the need for hemodialysis in 10.3%. Conclusion: This is the first Brazilian study to evaluate risk factors for ED in newly diagnosed AML in the public setting, as well as to address which events explain such higher mortality in comparison to American and European reports. In line with the literature, age itself was not associated with mortality when adjusted for other variables such as CCI and genetic stratification. Interestingly, we found that the baseline CRP levels are significantly correlated with ED, highlighting the role of infection and inflammation at the AML diagnosis. Disclosures No relevant conflicts of interest to declare.

Risk factors for tumor lysis syndrome in childhood acute myeloid leukemia treated with a uniform protocol without rasburicase prophylaxis

2015 ◽  
Vol 56 (7) ◽  
pp. 2193-2195 ◽  
Author(s):  
Kenji Kishimoto ◽  
Ryoji Kobayashi ◽  
Mizuho Ichikawa ◽  
Hirozumi Sano ◽  
Daisuke Suzuki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tumor Lysis Syndrome ◽  
Tumor Lysis ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

Mechanisms of Suppression Used by Regulatory T Cells in Patients Newly Diagnosed with Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2938-2938 ◽  
Author(s):  
Miroslaw J Szczepanski ◽  
Marta Szajnik ◽  
Malgorzata Czystowska ◽  
Magis Mandapathil ◽  
Ann Welsh ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Regulatory T Cells ◽  
Myeloid Leukemia ◽  
Neutralizing Antibodies ◽  
Hematologic Malignancies ◽  
Cell Contact ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract An elevated frequency of CD4+CD25high regulatory T cells (Treg) has been reported in the peripheral blood in patients with various solid tumors and hematologic malignancies. Although the increase in Treg seems to be a characteristic feature of most tumors, the functional role of Treg and the mechanisms of suppression, especially in patients with hematologic malignancies, have been less well defined. We investigated Treg-mediated suppression and the responsible mechanisms in thirty newly diagnosed acute myeloid leukemia (AML) patients prior to any treatment and twenty five healthy donors (NC). The percentage of circulating CD4+ CD25high Treg was higher (p <0.0001) in the AML patients (4.5 ±0.2%, range 1.7–8.2%) compared to NC (1.5 ± 0.08%, range 0.9–3.1 %). To evaluate the suppressive function, CD4+CD25high T cells (S) were co-cultured with sorted, CFSE-labeled autologous CD4+CD25high T cells (R) at different S/R ratios. Suppression mediated by Treg co-incubated with proliferating autologous responders was significantly higher (p<0.001) in AML than that mediated by control Treg. To evaluate the role of cytokines produced by Treg in suppression and a need for cell-to- cell contact, transwell analysis of S/R co-cultures was performed. Co-incubation in the presence of transwell inserts (TRI) resulted in significant reduction of suppression (p<0.05), and the addition of neutralizing antibodies to IL-10 and TGF-β1 in the presence of TRI further decreased suppression mediated by Treg. These data suggest that both immunoinhibitory cytokine production and cell-to-cell contact are necessary for suppression. To explore other potential mechanisms of Treg suppression, we evaluated the expression by Treg of ectonucleotidases CD39 and CD73 and the capability of Treg to produce adenosine. CD4+CD25high T cells of AML patients had higher expression (p<0.01) of CD39 and more efficiently hydrolyzed ATP to adenosine relative to Treg in NC. These data indicate that various mechanisms of suppression may be utilized by Treg in patients with AML. The increase frequency of Treg mediating potent suppression by various mechanisms is likely to play a role in host anti-tumor immune responses. Therefore, modulation of the frequency and functions of Treg might provide new immunotherapeutic approaches in AML.

scholarly journals An External Validation Study for Current Risk Scoring Models in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3861-3861
Author(s):  
Chia-Jen Liu ◽  
Hong Ying-Chung ◽  
Chiu-Mei Yeh ◽  
Chun-Kuang Tsai ◽  
Liang-Tsai Hsiao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Group Performance ◽  
Early Mortality ◽  
Prognostic Models ◽  
Newly Diagnosed ◽  
Discrimination Ability ◽  
Elderly Aml ◽  
Acute Myeloid

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm in the elderly. The high mortality in elderly AML patients is reported to be associated with old age, poor performance status, and several disease characteristics. Several risk stratification models have been reported. Our aims were to explore risk factors for early mortality in older AML patients and compare the discrimination ability of existing prognostic models. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital, a national medical center in Taiwan, between July 1, 2008 and May 31, 2017. Our primary endpoint was early mortality, defined as death within two months after initial AML diagnosis. Performance of several existing scoring systems were compared by using the Akaike information criteria (AIC) and Bayesian information criterion (BIC) calculations. Model discrimination ability was also estimated by Harrell's C statistics. Results A total of 478 AML patients were diagnosed during the eight-year follow-up period. After excluding young patients (age < 60) and those without a histopathologic diagnosis, the final cohort included 277 patients. The median age was 74 (range 60-96), and 171 (61.7%) of them were male. One hundred sixteen patients (41.9%) had Eastern Cooperative Oncology Group performance (ECOG) ≥ 2 and 33.9% patients had poor/adverse cytogenetics or molecular abnormalities. The two-month mortality rate was 29.9% (95% confidence interval [CI] 24.8%-35.9%). Age ≥ 80 (adjusted HR 1.95, 95% CI 1.12-3.42), having an antecedent hematologic disorder (adjusted HR 1.86, 95% CI 1.01-3.43), ECOG ≥ 2 (adjusted HR 2.06, 95% CI 1.20-3.54), complex karyotype (adjusted HR 3.13, 95% CI 1.76-5.55), BM blasts ≥ 70% (adjusted HR 1.79, 95% CI 1.02-3.13), WBC ≥ 100 ×109/L (adjusted HR 3.27, 95% CI 1.58-6.75), and creatinine > 1.3 mg/dL (adjusted HR 2.04, 95% CI 1.23-3.39) were identified as independent predictors for early mortality in the multivariate analysis. Furthermore, we systematically reviewed existing prognostic models for elderly AML. We found five scoring models that don't require additional specific examinations beyond clinical practice and later applied them to our elderly AML cohort. The performance of the five models is shown in Table. Kantarjian's prognostic model (Kantarjian H, et. al. Blood 2010) had the highest Harrell's C statistic and the ALMA score (Ramos F, et. al.Leukemia Research 2015) had the lowest AIC and BIC compared with the other prognostic models. Conclusion We identified seven risk factors for early mortality and compared the performance of five prognostic models for elderly AML patients. The finding may help clinicians to stratify patients and initiate appropriate management. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Features and Cytoreduction Therapy in Children with Newly Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2295-2295
Author(s):  
Georgios E. Christakopoulos ◽  
Kendra N Walker ◽  
Lei Wang ◽  
Clifford Takemoto ◽  
Yan Zheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Blood Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Tumor Lysis Syndrome ◽  
Newly Diagnosed ◽  
Tumor Lysis ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Abstract Background Hyperleukocytosis is observed in 5% to 20% of patients with newly diagnosed acute myeloid leukemia (AML) and is associated with an increased risk of early complications and mortality. While being used frequently in patients with AML and hyperleukocytosis, the clinical utility of leukapheresis has not been conclusive. Low-dose chemotherapy has also been used recently as a cytoreduction method in these patients, but the data are limited. Objectives: To describe and compare the clinical and laboratory characteristics, early adverse events, and outcomes of children with newly diagnosed AML and hyperleukocytosis according to cytoreductive methods; leukapheresis, low dose chemotherapy (cytarabine), or no intervention. Methods: We studied patients with newly diagnosed AML treated on three multi-institutional St. Jude protocols, AML97, AML02, and AML08, between 1997 and 2017. Hyperleukocytosis was defined as white blood cell (WBC) counts of 100 x 10 9/L or higher at diagnosis. The decision of cytoreductive treatment was made as the discretion of the treating physician. Leukoreduction was used in the AML97 and AML02 studies, and cytarabine (100mg/m 2/dose every 12 hours) was the first choice for AML08 study. We reviewed baseline clinical characteristics and laboratory data (complete blood cell counts [CBC], chemistries, coagulation) and adverse effects (grade 3 or higher on neurologic, renal, respiratory, and hemorrhagic complications based on Common Terminology Criteria for Adverse Events) from diagnosis to day 14 of protocol-based chemotherapy. Cairo-Bishop criteria was used for laboratory/clinical tumor lysis syndrome. The time from the first CBC to administration of protocol-based chemotherapy was calculated. Results: A total of 49 patients were identified: 8 patients in AML97, 19 in AML02, and 22 in AML08) (Table). The age at diagnosis was 10.8 years with a median initial WBC count of 157.6 x 10 9/L; CNS (CNS 2, 3 or traumatic lumbar puncture with blasts) was seen in 29 (59.2%) cases. FAB M4 or M5 subtype was found in 30 patients (61.2%), 11q23 abnormalities in 15 (30.6%) and inv(16) in 8 (16.3%). In regards to leukoreduction method, 16 patients received leukapheresis (14 patients in AML97/02 and 2 in AML08), 18 cytarabine (all in AML08) and 1 hydroxyurea (in AML08); 14 did not receive leukoreduction (13 patients in AML97/02 and 1 in AML08). Leukapheresis was used more often in patients with higher diagnostic WBC counts (218.7 x 10 9/L) than those treated with cytarabine (152.9 x 10 9/L) or without intervention (127.3 x 10 9/L) (P&lt;0.001). The decrease of WBC counts (%) before and after intervention was more pronounced among patients treated with cytarabine than those treated with leukapheresis (75% vs. 48.5%, P=0.03). When decreases in WBC counts were evaluated from the first CBC to the initiation of protocol therapy, cytarabine treatment was associated with more decreases in WBC counts from baseline (84.8%) than leukapheresis (46.7%) or no intervention (1.8%) (P&lt;0.001). Patients who received cytarabine intervention had a longer median time from the first CBC to initiation of protocol therapy (95.2 hours) compared to those who received leukapheresis (28.1 hours) and no intervention (20.4 hours) (P&lt;0.001). No early deaths were observed from the time of diagnosis to two weeks after initiation of protocol chemotherapy, and no statistically significant differences were noted in the incidences of neurologic, pulmonary, renal, hemorrhagic events, or laboratory/clinical tumor lysis syndrome among these three groups. Conclusion: Low-dose cytarabine treatment appears to be a safe and effective mean of cytoreduction for patients with AML and hyperleukocytosis. Further studies are needed to determine if this approach is preferable among patients treated with contemporary treatment. Figure 1 Figure 1. Disclosures Pui: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Data Monitoring Committee.

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