Early Mortality In Hyperleukocytosis In Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2647-2647 ◽  
Author(s):  
Sapna Oberoi ◽  
Thomas Lehrnbecher ◽  
Robert Phillips ◽  
Johann K. Hitzler ◽  
Marie-Chantal Ethier ◽  
...  
Keyword(s):  
Death Rate ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Meta Analysis ◽  
Early Death ◽  
Early Mortality ◽  
Confounding Bias ◽  
Meta Regression ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Abstract Background Hyperleukocytosis in acute myeloid leukemia (AML) is associated with early deaths, typically related to respiratory failure and intracranial ischemia/hemorrhage. Various interventions for leukoreduction including leukapheresis, low-dose chemotherapy and hydroxyurea have been used in an attempt to decrease mortality. However, there are no randomized trials and observational trials are biased. We undertook a systematic review and meta-analysis to evaluate the effect of these interventions using an “intent-to-treat” approach and classifying studies as always, sometimes and never using these interventions. Objectives The primary objective was to describe the proportion of early deaths in patients with AML with an initial WBC ≥ 100,000x109/L stratified by the approach to leukapheresis and hydroxyurea/low dose chemotherapy (universal, sometimes or never). The secondary objective was to compare the proportion of early deaths in patients who did and did not receive leukapheresis. Methods Electronic searches of Ovid Medline from 1980 to July 12, 2013, EMBASE from 1980 to July 12, 2013 and Cochrane Central Register of Controlled Trials until June 2013 were conducted. Studies were included if: (1) Population included patients with AML; and (2) Either described the proportion of patients with early deaths in patients with an initial WBC ≥ 100,000x109/L or compared the proportion of early deaths by receipt of leukapheresis in patients using the same initial WBC threshold. Studies including solely acute promyelocytic leukemia (APML) patients were excluded. The pre-specified subgroups in the evaluation of early death proportions were whether leukapheresis and low-dose chemotherapy/hydroxyurea were intended to be applied universally, sometimes or never in hyperleukocytosis. These subgroups were defined based on the study’s stated policy independent of the number of patients actually receiving the intervention. Two investigators assessed the quality of the included studies for selection and confounding bias using the Hayden framework. Synthesis of proportions was conducted using RevMan. Meta-regression was conducted in which the natural log of the proportion of early deaths was modelled. Heterogeneity was assessed by visual inspection and I2. Results Twenty studies representing 1427 patients were included in the final meta-analysis. Overall, the proportion of early deaths (19 studies, 1281 patients) was 19.9% (95% CI: 14.7-25.1). Table 1 illustrates that neither leukapheresis strategy nor hydroxyurea/low dose chemotherapy influenced the early death rate. Meta-regression evaluating the percent of patients receiving leukapheresis showed no relationship with early death rate (odds ratio 1.01, 95% CI: 0.99-1.02; P=0.249). Evaluation of leukapheresis within studies included 7 studies of which 6 were at high risk of confounding bias and sufficiently heterogeneous to not permit synthesis. Conclusion Early mortality related to hyperleukocytosis is high and is not influenced by universal or selected use of leukapheresis or low-dose chemotherapy/hydroxyurea. This meta-analysis does not support these interventions for patients with AML and hyperleukocytosis. Novel approaches are required to decrease mortality. Disclosures: Lehrnbecher: Gilead: Honoraria; MSD: Honoraria; Pfizer: Honoraria; Astellas: Honoraria.

Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: A systematic review and meta-analysis

2014 ◽  
Vol 38 (4) ◽  
pp. 460-468 ◽  
Author(s):  
Sapna Oberoi ◽  
Thomas Lehrnbecher ◽  
Bob Phillips ◽  
Johann Hitzler ◽  
Marie-Chantal Ethier ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Meta Analysis ◽  
Early Mortality ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Improvements in the Early Death Rate in Younger Acute Myeloid Leukemia Patients Following Initial Therapy: A SEER Database Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3696-3696
Author(s):  
Mary-Elizabeth M. Percival ◽  
Li Tao ◽  
Bruno C Medeiros ◽  
Christina A Clarke
Keyword(s):  
Acute Myeloid Leukemia ◽  
Death Rate ◽  
Myeloid Leukemia ◽  
Early Death ◽  
Early Mortality ◽  
Younger Patients ◽  
The Past ◽  
Time Period ◽  
Over Time ◽  
Acute Myeloid

Abstract Purpose: Acute myeloid leukemia (AML) is treated with conventional induction chemotherapy shortly after diagnosis in most patients less than or equal to 65 years old, most commonly combining infusional cytarabine with an anthracycline. Fatalities from infectious or bleeding complications related to cytopenias within 30 days of diagnosis (known as early death or treatment-related mortality) are routinely reported in these patients. Recent data from patients treated on clinical trials suggested a decline in the early death rate over the past two decades. It is unknown if a similar improvement has been observed in the general population. Methods: We examined the 30-day mortality and overall survival (OS) in a large population-based series of 9,380 AML patients reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Included patients were diagnosed with AML between 1973 and 2010, were between the ages of 18 and 65 at diagnosis, and were treated with chemotherapy. We stratified patients by age and geographic location at diagnosis. Results: We observed a significant improvement in median OS from 6 months (95% CI 5-7) in 1973-1977 to 23 months (95% CI 16-20) in 2008-2010 (p < 0.001). During the same study period, the 30-day mortality rate declined from 18.7% among patients diagnosed in 1973-1977 (95% CI 16.4-21.2%) to 5.8% for those diagnosed in 2008-2010 (95% CI 4.5-7.6%) (p < 0.001). Weighted linear regression analysis revealed a strong linear trend in the 30-day mortality rate (R2 = 0.78), with an average annual decrease in the early death rate of 0.4% per year throughout the study period (β = 0.3755; Figure 1). When analyzed by age, the largest absolute improvements were noted in older patients (approximately 15% absolute decrease in 30-day mortality for patients aged 51-65 over study period). Though location at diagnosis significantly influenced 30-day mortality in 1973-1977, these differences in early death rate were no longer evident in the most recent time period (2008-2010). The patient characteristics remained stable over time with a median age at AML diagnosis of 50. Conclusion: Over the past four decades, significant improvements in median OS and 30-day mortality have occurred in our large cohort of younger patients (less than or equal to 65 years) with newly diagnosed AML undergoing chemotherapy. The largest improvements over time were noted in the oldest age group and in regions with intermediate to high early mortality in the earliest time period (1973-1977). The decrease in 30-day mortality appears to partially account for the increase in median OS observed over the past 4 decades. These data suggest that risk of early mortality has decreased and should not prevent younger patients with AML from receiving aggressive initial treatment modalities. Figure 1. 30-day mortality (%, 95% CI) for AML patients, by year of diagnosis, SEER 9 Registries, 1973-2010. Figure 1. 30-day mortality (%, 95% CI) for AML patients, by year of diagnosis, SEER 9 Registries, 1973-2010. Disclosures No relevant conflicts of interest to declare.

scholarly journals Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

2021 ◽  
Vol 20 ◽  
pp. 153473542110026
Author(s):  
Andrana K. Calgarotto ◽  
Ana L. Longhini ◽  
Fernando V. Pericole de Souza ◽  
Adriana S. Santos Duarte ◽  
Karla P. Ferro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Green Tea ◽  
Regulatory T Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Related Factor ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

scholarly journals Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingyu Xu ◽  
Shujiao He ◽  
Li Yu
Keyword(s):  
Systematic Review ◽  
Myeloid Leukemia ◽  
Retrospective Cohort ◽  
Meta Analysis ◽  
Early Death ◽  
Gemtuzumab Ozogamicin ◽  
Free Survival ◽  
Retrospective Cohort Studies ◽  
Clinical Benefits ◽  
Acute Myeloid

BackgroundPrevious trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.MethodsPubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.ResultsFifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p &lt; 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of &lt;70 years (p &lt; 0.05), de novo AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (&lt;6 mg/m2) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m2) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).ConclusionsThese data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.Systematic Review Registration[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].

scholarly journals Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy

2019 ◽  
Vol 6 (3) ◽  
pp. 469-479 ◽  
Author(s):  
Yixin Hu ◽  
Aili Chen ◽  
Xinchang Zheng ◽  
Jun Lu ◽  
Hailong He ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Randomized Study ◽  
Remission Induction ◽  
Molecular Response ◽  
Standard Chemotherapy ◽  
Low Dose Chemotherapy ◽  
The Impact ◽  
Acute Myeloid

Abstract Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, P = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; P = 0.99) and overall (70.3 vs. 74.6%, P = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs (P < 0.001); 15.5 vs. 22.0 d for platelets (P < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF (n = 9) or SDC (n = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.

Clinical Features, Complications, and Early Treatment Outcome of Pediatric Acute Myeloid Leukemia with Hyperleukocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4505-4505
Author(s):  
Hiroto Inaba ◽  
Ying Fan ◽  
Stanley Pounds ◽  
Jeffrey E. Rubnitz ◽  
Raul C. Ribeiro ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
Leukocyte Count ◽  
Early Death ◽  
Pulmonary Complications ◽  
Early Mortality ◽  
Remission Induction ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Patients with acute myeloid leukemia (AML) and hyperleukocytosis are at increased risk of early death from neurological and pulmonary complications due to leukostasis. Although leukapheresis is often used for rapid cytoreduction in these patients, a recent adult study showed no difference in the rate of early mortality between patients who underwent leukapheresis and historical controls. The scarcity of information about leukapheresis in childhood AML led us review our experience of 106 children with AML and hyperleukocytosis (i.e., initial leukocyte count ≥ 100 × 109/L) treated between 1968 and 2002. The presenting clinical features, early complications, and clinical outcomes during the first 2 weeks of remission induction therapy were analyzed according to two treatment eras: early (1968–1982) vs. recent (1983–2002), when leukapheresis was available. The entire cohort had a median age of 9.7 years (range, 0–19.9 years); initial leukocyte count of 161 × 109/L (100 to 1,600); hemoglobin concentration of 8.2 g/dL (2.9–15.4); and platelet count of 38.5 × 109/L (0 to 300). The presenting features were comparable between patients treated in the two eras with the exception of higher hemoglobin concentrations among those treated in the recent era (p=0.03). Platelet transfusion prior to chemotherapy was used more often in the recent era (p=0.001). Half of the cases (53 of 106) had FAB M4 or M5 subtypes. Twenty-one patients (19.8%) had grade 3 or 4 neurological, respiratory, and/or renal complications (according to NCI common criteria) at initial presentation, and 35 patients (33%) had one or more of these complications during the first 2 weeks after diagnosis (17 neurological; 20 respiratory; 16 renal). The frequency of the complications did not differ significantly between patients treated in the two eras. Patients with FAB M4/M5 AML were significantly more prone than others to respiratory (p=0.005) and renal (p=0.0002) complications during the first two weeks of therapy. Seventeen patients (16%) died during the first 2 weeks after diagnosis. The rate of early death was significantly higher in the early era than in the recent era (16/70 vs. 1/36, p=0.01). The time between admission and initiation of chemotherapy was significantly shorter (20.2 vs. 33.6 hours, p&lt;0.0001), and the reduction of leukocyte count before chemotherapy was significantly less (−3 × 109/L vs. −77.1 × 109/L, p&lt;0.0001) in patients treated in the early era, as compared to those from the recent era. Among patients treated in the recent era, the 20 who underwent leukapheresis had a higher initial leukocyte count (205.9 × 109/L vs. 115.5 × 109/L, p&lt;0.0001) than the 16 who did not undergo the procedure. Although the incidence of acute complications did not differ between the two eras, the rate of early death was markedly decreased in the recent era (from 23% to 2.8%), suggesting that leukapheresis/exchange transfusion might have prevented some early deaths. Our results suggest that improved supportive care, including the use of leukapheresis, decreases early mortality caused by leukostasis, especially in patients with M4 or M5 subtypes of AML.

Efficiency Of 7+3 Chemotherapy Followed By Donor Lymphocyte Infusion In Patients With Relapsed Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4500-4500
Author(s):  
Rashit Bogdanov ◽  
Larisa Mendeleeva ◽  
Elena Parovichnikova ◽  
Larisa Kuzmina ◽  
Irina Galtseva ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Relapses after allogeneic stem cell transplantation (allo-SCT) are the main cause of treatment failure in acute myeloid leukemia (AML). Chemotherapy with subsequent donor lymphocyte infusions (DLI) is considered to be the optimal approach for complete remission (CR) achievement and induction of “graft versus leukemia” effect. There is a tendency to use low-dose chemotherapy (i.e. Low-dose Ara-C) in this setting because of less toxicity. However the efficacy of low-dose chemotherapy is not satisfactory and leads to 45-67% CR rate. In this study we apply intensive chemotherapy (7+3) followed by DLI in aplasia in with relapsed AML. Aim To investigate the efficacy of DLI perfomed in neutropenia after reinduction chemotherapy 7 +3 (Cytarabine 100 mg/m^2 every 12 hours daily for 7 days, and Idarubicin 12 mg/m^2 daily on days 1, 2, and 3) in AML patients (pts) with overt relapse after allo-SCT. Methods The study comprised 16 AML patients. The median age was 31 years (16 - 57 years), male – 11 female - 5. Twelve patients underwent allo-SCT in first remission, 4 pts - in overt relapse of AML. Allo-SCT was carried out from HLA-matched sibling donor in all pts. Myeloablative conditioning regimen was performed in 10 pts. Reduced intensity conditioning (RIC) - in 6 pts. AML relapse occurred at a median 4,7 months (range from 1 to 51 months) after allo-SCT. Patients received DLI at day 7 (7-14 days) after chemotherapy during myelotoxic agranulocytosis. The number of infusions ranged from 1 to 4 (median 2 DLI) per patient. DLI after chemotherapy were carried out twice in 1 patient due to the second relapse. So we analysed 17 cases of relapse in 16 pts. Total amount of the CD3+cells varied from 1 to 16,7x10^7 CD3+cells/kg (median 6,0x10^7 CD3+ cells/kg). The interval between DLI was 1-4 weeks. All pts received 2 - 6 MUE Interleukin-2 (IL-2) subsequently after DLI. Chimerism was monitored by PCR analysis (VTTR and STR) and by FISH – analysis for centromers of X and Y – chromosomes after DLI each 2-4 weeks up to 6 months, then every 3 months. Results Complete remission with 100% donor chimerism was achieved in 14 (82%) out of the 17 cases. There were no toxic deaths, 3 pts died in leukemia progression. All pts developed severe infections in neutropenic phase (mucositis, pneumonia, sepsis), but they were cured. Eight pts (57%) out of 14 developed a relapse in 5 months after DLI (from 1 to 17 months) and 6 pts (35%) remained in remission. Follow-up period was 12 months (1 - 124 months). Median overall survival constituted 15 months. Acute graft versus host disease (GVHD) after DLI was diagnosed in 8 patients 47% (6 - I-II grade; 2 - III-IV grade). Chronic GVHD was diagnosed in 8 pts (47%): limited -6 pts (35%), extensive - 2 pts (12%). Conclusion Our data show that despite myelotoxicity and infections 7+3 and subsequent DLI+ IL-2 is an effective treatment for AML pts with overt relapse after allo-SCT. 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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