Early mortality rate (EMR) and complications in adults with acute myeloid leukemia (AML) in California.

The therapeutic strategies for acute myeloid leukemia (AML) patients ineligible for remission induction chemotherapy have been improving in the past decade. Therefore, it is important to define ineligibility for remission induction chemotherapy. We retrospectively assessed 153 consecutive adult de novo AML patients undergoing remission induction chemotherapy and defined early mortality as death within the first 60 days of treatment. The 153 patients were stratified into the early mortality group (n = 29) and the non-early mortality group (n = 124). We identified potential factors to which early mortality could be attributed, investigated the cumulative incidence of early mortality for each aspect, and quantified the elements. The early mortality rate in our study cohort was 19.0%. Age ≥ 65 years (odds ratio (OR): 3.15; 95% confidence interval (CI): 1.05–9.44; p = 0.041), Eastern Cooperative Oncology Group performance status ≥ 2 (OR: 4.87; 95% CI: 1.77–13.41; p = 0.002), and lactate dehydrogenase ≥ 1000 IU/L (OR: 4.20; 95% CI: 1.57–11.23; p = 0.004) were the risk factors that substantially increased early mortality in AML patients. Patients with two risk factors had a significantly higher early mortality rate than those with one risk factor (68.8% vs. 20.0%; p < 0.001) or no risk factors (68.8% vs. 9.2%; p < 0.001). In conclusion, older age, poor clinical performance, and a high tumor burden were risks for early mortality in AML patients receiving remission induction chemotherapy. Patients harboring at least two of these three factors should be more carefully assessed for remission induction chemotherapy.

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Hydroxyurea in the Early Management of Acute Myeloid Leukemia and Hyperleukocytosis.

Blood ◽

10.1182/blood.v110.11.4368.4368 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4368-4368 ◽

Cited By ~ 3

Author(s):

Asmaa M. Quessar ◽

Nisrine R. Khoubila ◽

Raul C.U. Ribeiro ◽

Mohamed A. Rachid ◽

Saadia D. Zafad ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Mortality Rate ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Early Mortality ◽

Early Management ◽

The Mean ◽

Wbc Count ◽

Acute Myeloid

Abstract BACKGROUND: Patients with acute myeloid leukemia (AML) and hyperleukocytosis are at high risk of early mortality due to pulmonary, renal, and central nervous system complications. Leukapheresis and low-dose continuous infusion of cytarabine and hydroxyurea (HU) have been used but their advantages and limitations are not well characterized. The University hospital in Casablanca, Morocco has a limited number of beds, and hence admissions must be prioritized. Here we report the effects of HU on the white blood cell (WBC) count and early mortality rate of patients with hyperleukocytic AML. METHODS: Between April 2003 and December 2006, patients with AML were enrolled on the AML-MA2003 protocol (2 induction courses of cytarabine and daunorubicin and 2 postremission courses that include intermediate-dose cytarabine). Patients with AML and hyperleukocytosis (WBC count >50 x 109/L) were immediately started on HU (50 mg/kg/day orally x 4 days), regardless of hospital bed availability. Response was evaluated after 4 days of HU; patients were considered responders if >50% reduction of the initial WBC count was observed. RESULTS: Ninety of 260 (34.6%) patients enrolled had hyperleukocytosis. Three patients were excluded, induction therapy started on the day of admission. Therefore, 87 patients (48 females, 39 males) were evaluable. The mean age was 32 years (range, 2–60); 29% were children (ages 2–20 years). The mean initial WBC count was 104x109/L (range 50–260 x109/L); 37 (42.5%) patients had WBC counts > 100x109/L. The French-American-British subtypes were M1 (45%), M2 (26%), M4 (12%), M5 (7%), and M0, M3, M6 and M7 (2.5% each); 5 cases were unclassified. Karyotypes determined for 65/87 cases revealed 13 (20%) favorable karyotypes [9 had the t(8;21); 3 had inv16; 1 had the t(15;17)], 30 (46%) intermediate-risk karyotypes, including normal karyotypes, and 22 (34%) unfavorable-risk karyotypes. Sixty-two (71%) patients were classified as responders. In an additional 3, the WBC count was reduced 25%–50%. In 22 (25%) patients, including 4 whose WBC counts increased, HU showed no cytoreductive effect. The mean WBC count after 4 days of HU was 24 x 109/L (range, 1.5–125 x109/L); 15 (17%) patients’ WBC counts remained >100x109/L. Four patients developed acute tumor lysis syndrome (TLS) (hyperuricemia and renal dysfunction) in response to HU. There were 5 (8%) early deaths (mean, 7 days after the start of HU; range, 4–14 days). All 5 patients had WBC counts > 100x109/L at diagnosis, and only 1 was a responder. This mortality rate does not differ from that (9%) observed among the 170 protocol patients who did not have hyperleukocytosis. Causes of death included infection (n=1), pulmonary and CNS leukostasis (n=1 each), TLS (renal failure and hyperkalemia, n=1), and intracranial hemorrhage (n=1). Among several factors (age, sex, FAB type, karyotype, WBC counts), only WBC count of ≤ 100x109/L was significantly associated with response to HU (P=0.01). The complete remission rate after first course of induction therapy was 43.5% for responders and 16% for non-responders (P=0.02). CONCLUSION: HU given orally for 4 days rapidly reduces the WBC count in pediatric and adult AML with hyperleukocytosis. The early mortality rate in this high-risk group treated with HU compares favorably with rates reported for similar patients. It remains to be determined whether initial response to HU is associated with overall outcome in AML.

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Reasons for Decreasing Early Mortality in Acute Myeloid Leukemia: An Epidemiological Study from the Swedish Acute Leukemia Registry

Blood ◽

10.1182/blood.v126.23.3748.3748 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3748-3748

Author(s):

Stefan Deneberg ◽

Ebba Lundin ◽

Vladimir Lazarevic ◽

Lina Benson ◽

Bertil Uggla ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Treatment Group ◽

Mortality Rate ◽

Myeloid Leukemia ◽

Performance Status ◽

Early Mortality ◽

Induction Treatment ◽

Treatment Intensity ◽

Time Period ◽

Acute Myeloid

Abstract Purpose The rates of early mortality (EM) are high in patients receiving intensive chemotherapy for acute myeloid leukemia (AML). Decreasing EM-rates over time have recently been reported. The reason for the improvement is however elusive and generally attributed to better supportive antibiotic and antifungal treatment. We wanted to investigate this further in a population-based material and if possible find factors associating with improvement. Patients and Methods We investigated temporal trends of early mortality defined as death within 30 days of diagnosis in the Swedish AML-registry. "Day of diagnosis" was defined as the day of the diagnostic bone marrow aspiration. The annual incidences of EM in 6034 non-promyelocytic AML patients (median age 71 years) in Sweden 1997-2014 were analyzed. Plots showing unadjusted cubic smoothing splines were constructed. Generalized estimation equation models were used to generate rate ratios with calendar year as the independent variable with 1997 as the reference year. Adjustments were made for age, gender, center, AML class (snomed), AML type (de novo/therapy related or secondary AML), WHO performance status, cytogenetic risk and treatment intensity. To avoid bias due to baseline characteristics missing not at random, multiple imputation (n=10) was performed for variables with missing data. A predefined subgroup analysis based on treatment intensity was also performed. Results We found an overall modest but significant reduction of early mortality with a yearly rate ratio (RR) of 0.99 (95% CI: 0.98-1.00, p=0.026) of the unadjusted EM (figure 1). Separate analysis of patients given induction treatment compared to those receiving palliative care showed that the reduction of early mortality was exclusively seen in the induction treatment group. Here, the crude yearly reduction of early mortality was RR=0.97 (95% CI:0.94-0.99, p=0.01) whereas there was no reduction in the palliative treatment group; RR=1.01(95% CI:0.99-1.02, p=0.27) (figure 2). Interestingly, the decrease of the early mortality rate was lost in the adjusted model; RR= 1.00 (95% CI:0.99-1.01, p=0.37) for the whole cohort. In univariate analysis two factors impacted the model in the direction of decreased EM; improved WHO performance status at diagnosis and a modest increase of low-risk cytogenetic patients (figure 3). Notable was also a slight decrease of the number of intensively treated patients during the time period. When adjusting for WHO PS and cytogenetic risk, subgroup analysis even showed an increased adjusted early mortality rate among palliatively treated patients, RR=1.02 (95%CI: 1.01-1.03, p=0.001) while there was no difference among the intensively treated patients, RR=1.00 (95% CI: 0.97-1.02, P=0.81) (figure 2). Simply put, if patients would have retained the same case mix as in 1997 the decrease of EM we see would not have occured. Caveats are that we assume that the WHO performance scale has been applied consequently during the study period. We have no indications otherwise and the scale is regarded as a robust and well validated instrument, so we consider this risk minor. The decrease in the number of intensively treated patients may also indicate a change in the selection process that theoretically could improve outcomes, for instance a more widespread use of EM risk assessment scales. This is however nothing the authors are aware of has happened on a general level during the time period. We conclude that a major factor associating with the decrease of early mortality in AML is a general improvement of performance status of patients at diagnosis. Disclosures No relevant conflicts of interest to declare.

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Leukapheresis and cranial irradiation in patients with hyperleukocytic acute myeloid leukemia: No impact on early mortality and intracranial hemorrhage

American Journal of Hematology ◽

10.1002/ajh.20939 ◽

2007 ◽

Vol 82 (11) ◽

pp. 976-980 ◽

Cited By ~ 54

Author(s):

Ming-Chih Chang ◽

Tsai-Yun Chen ◽

Jih-Luh Tang ◽

Yii-Jenq Lan ◽

Tsu-Yi Chao ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Intracranial Hemorrhage ◽

Myeloid Leukemia ◽

Cranial Irradiation ◽

Early Mortality ◽

Acute Myeloid

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Varying intensity of postremission therapy in acute myeloid leukemia

Blood ◽

10.1182/blood.v79.8.1924.bloodjournal7981924 ◽

1992 ◽

Vol 79 (8) ◽

pp. 1924-1930 ◽

Cited By ~ 2

Author(s):

PA Cassileth ◽

E Lynch ◽

JD Hines ◽

MM Oken ◽

JJ Mazza ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Mortality Rate ◽

Maintenance Therapy ◽

Myeloid Leukemia ◽

High Dose ◽

Allogeneic Bone ◽

Consolidation Therapy ◽

High Dose Cytarabine ◽

Postremission Therapy ◽

Acute Myeloid

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6- thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four- year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

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Early mortality in acute myeloid leukemia

Leukemia Research ◽

10.1016/j.leukres.2015.02.003 ◽

2015 ◽

Vol 39 (5) ◽

pp. 505-509 ◽

Cited By ~ 11

Author(s):

Andrew Hahn ◽

Smith Giri ◽

George Yaghmour ◽

Mike G. Martin

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Early Mortality ◽

Acute Myeloid

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Usefulness of Charlson Comorbidity Index to Predict Early Mortality and Overall Survival in Older Patients With Acute Myeloid Leukemia

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2020.07.002 ◽

2020 ◽

Vol 20 (12) ◽

pp. 804-812.e8 ◽

Cited By ~ 1

Author(s):

Prajwal Dhakal ◽

Valerie Shostrom ◽

Zaid S. Al-Kadhimi ◽

Lori J. Maness ◽

Krishna Gundabolu ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Charlson Comorbidity Index ◽

Older Patients ◽

Myeloid Leukemia ◽

Early Mortality ◽

Comorbidity Index ◽

Acute Myeloid

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Clofarabine Does Not Impact Negatively the Outcomes of Patients with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Stem Cell Transplantation and Is Not Associated with Higher Liver Toxicity Rates Compared with Standard Chemotherapy

Blood ◽

10.1182/blood.v118.21.1489.1489 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1489-1489

Author(s):

Michael S Mathisen ◽

Hagop M. Kantarjian ◽

Elias Jabbour ◽

Guillermo Garcia-Manero ◽

Farhad Ravandi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Liver Toxicity ◽

Early Mortality ◽

Cell Transplant ◽

Younger Patients ◽

Early Relapse ◽

Post Transplant ◽

Acute Myeloid

Abstract Abstract 1489 Background: The purine nucleoside analog clofarabine is currently being actively investigated at the M.D. Anderson Cancer Center (MDACC) in combination with idarubicin and cytarabine (CIA) as frontline therapy for younger patients with newly diagnosed acute myeloid leukemia (AML). Hepatotoxicity (i.e. elevation of transaminases and/or bilirubin) is one of the primary adverse events associated with clofarabine and rare instances of severe hepatotoxicity as well as veno-occlusive disease (VOD) have been reported. Allogeneic stem cell transplant (allo-SCT) is indicated for younger AML patients with poor risk features (i.e. adverse cytogenetics, diploid karyotype with FLT3 mutations) in first complete remission (CR). Allo-SCT also places the patient at risk of liver toxicity and VOD. Therefore, we investigated whether pre-transplant clofarabine-containing chemotherapy regimens adversely impacted the outcomes of younger patients with AML compared with those of patients pre-treated with non-clofarabine containing chemotherapy. Methods: We conducted a retrospective review comparing patients who underwent allo-SCT after receiving CIA (clofarabine 20 mg/m2 IV daily for 5 days, idarubicin 10 mg/m2 IV daily for 3 days, cytarabine 1,000 mg/m2 IV daily for 5 days) versus a non-clofarabine containing chemotherapy regimen (IA, idarubicin 12 mg/m2 IV daily for 3 days, cytarabine 1,500 mg/m2 via IV continuous infusion over 24 hours daily for 4 days). Consolidation cycles contained the same agents given according to an attenuated schedule. Patients were all receiving CIA or IA as their frontline regimen for AML. Variables that were extracted from the medical record include age, number of cycles of chemotherapy, CR rate, allo-SCT in CR, stem cell source, conditioning regimen, engraftment day, incidence of VOD, incidence of acute hepatotoxicity post-transplant, incidence of graft versus host disease (GVHD), early death, and early relapse. Results: Overall, 42 younger patients with AML undergoing allo-SCT were identified (n = 20 CIA, n = 22 IA). Patient age in both groups was similar, and there were more females in the IA group. Other patient and transplant characteristics were comparable between cohorts. Most patients underwent a matched related donor or matched unrelated donor allo-SCT (CIA 80% versus IA 82%), and the majority received busulfan-fludarabine based conditioning (CIA 70% versus IA 82%). Two patients in each group received clofarabine as part of their conditioning program. In general, there was not any appreciable difference in acute post-transplant hepatotoxicity or in the incidence of VOD (table 1). Moreover, early mortality, early relapse, and the incidence of GVHD were not increased in the pretransplant clofarabine group compared to the IA group. Conclusions: The use of clofarabine does not appear to impact negatively the outcome of younger patients with AML undergoing allo-SCT. There does not appear to be an increased risk of delayed engraftment, hepatotoxicity, VOD, GvHD, early relapse, or early mortality among patients with AML undergoing allo-SCT who receive pretransplant clofarabine. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v124.21.3696.3696 ◽

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.

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