Prognostic Value of Cytogenetics in Patients with Acute Myeloid Leukemia Aged More Than 60 Years at Diagnosis: Identification of Subgroups Taking Benefit from Intensive Chemotherapy. Results from a Large Single Center Retrospective Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3503-3503
Author(s):  
Nicolas Blin ◽  
Pascaline Talmant ◽  
Richard Garand ◽  
Francoise Accard ◽  
Philippe Moreau ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Rank Test ◽  
Intensive Chemotherapy ◽  
Secondary Aml ◽  
Log Rank Test ◽  
Group 3 ◽  
Standard Risk ◽  
Acute Myeloid

Abstract Cytogenetic analysis performed at diagnosis is known as the most important independent prognostic factor in adult acute myeloid leukemia (AML) treated with intensive chemotherapy. This major predictor of outcome has been mostly identified in younger patients who are categorized into three risk groups: favorable, intermediate and adverse. However, the prognostic value of chromosome abnormalities in elderly patients with AML aged 60 years or older has been evaluated in much fewer studies and overall prognosis remains very poor in this population with a very small number of long-term survivors using current standard chemotherapy. To further investigate the prognostic relevance of cytogenetic abnormalities in older patients, we reviewed 376 patients with de novo or secondary AML aged 60 years or more and available cytogenetic data at diagnosis. APL were excluded and no patient received allogeneic bone marrow transplantation. Of 376 patients, 280 (74%) received induction chemotherapy based on association with cytarabine (ara-C) and anthracyclins according to GOELAMS SA2, SA3, SA4 and SA2002 prospective trials between 1988 and 2005. Patients who were not treated with induction regimen received best supportive care or low dose ara-C. Overall complete remission rate was 42%, induction failure 38% and induction death 20%. With a median follow-up of 11.5 years for survivors, overall survival (OS) was 4.5% at 5 years (95% confidence interval [CI], 3.8%–5.8%) and disease free survival (DFS) was 4.3% at 5 years (95% CI, 3.7%–5.9%). Using a proportional hazards model with normal cytogenetics as reference group, 3 prognostic subgroups were identified for OS: low-risk (t(8;21) and inv(16)) in 20 of 280 patients (7%), standard-risk (+8, +11, −13/del(13q), t(11q23), +22, all in no complex karyotypes) in 175 of 280 patients (63%) and high-risk (−5/del(5q), −7/del(7q), −17/del(17p), −20/del(20q), +21, rare aberrations, complex≥3 and complex≥5) in 85 of 280 patients (30%). In multivariate analyses using a Cox model with backward selection procedure, high-risk cytogenetics (p<0.001), age>65 years (p=0.01), multilineage dysplasia on marrow at diagnosis (p=0.008) and white blood cell count (WBC) (p=0.03) appeared as independent prognostic factors on OS and DFS. Secondary AML did not appear as prognostic factor in multivariate analysis (p=0.18) but in a log-rank test, AML secondary to hematologic malignancy did significantly worse than AML secondary to solid tumors in both OS and DFS (p=0.01 and p=0.04, respectively). OS distribution between treated and untreated patients was compared using a log-rank test with homogeneous subgroups based on cytogenetic risk group and age. Three-years OS was significantly better in patients <70 years with standard-risk cytogenetics (p=0.008 if age<65years and p=0.02 if age <70 years). For high-risk cytogenetic group, 3-years OS was improved only in patients <65 years with WBC<30G/L (p=0.03). These results confirm the independent prognostic value of pretreatment karyotype, age >65 years, WBC and associated multilineage dysplasia in elderly patients with AML. Overall prognosis remains very poor and intensive chemotherapy does not improve OS in patients aged >70 years and high-risk cytogenetic groups.

Improved Treatment Results in High-Risk Pediatric Acute Myeloid Leukemia Patients After Intensification With High-Dose Cytarabine and Mitoxantrone: Results of Study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster 93

2001 ◽  
Vol 19 (10) ◽  
pp. 2705-2713 ◽  
Author(s):  
U. Creutzig ◽  
J. Ritter ◽  
M. Zimmermann ◽  
D. Reinhardt ◽  
J. Hermann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Rank Test ◽  
High Dose ◽  
Free Survival ◽  
Log Rank Test ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

PURPOSE: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. PATIENTS AND METHODS: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia–Berlin-Frankfurt-Münster (AML-BFM) 87. RESULTS: Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P = .01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P = .007; and 44% v 31%, P = .01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

scholarly journals Validation of Kantarjian (2010) Model for Intensive Chemotherapy in Older Adults with Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5258-5258
Author(s):  
Shawn Tahata ◽  
Annie Im ◽  
Michael Boyiadzis ◽  
Daniel Normolle
Keyword(s):  
Older Adults ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Historical Data ◽  
Performance Status ◽  
Risk Groups ◽  
Intensive Chemotherapy ◽  
Ecog Performance Status ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) carries a poor prognosis in older adults. Limited clinical trial data exist to support the use of conventional cytarabine-based regimens in this population, and practice standards have been extrapolated from studies in younger patients. Intensive chemotherapy in older adults is associated with high rates of treatment-related mortality and poor overall survival. In 2010, Kantarjian and colleagues developed a risk model for 8-week mortality using adverse prognostic risk factors, including age ≥80 years, complex karyotype (≥3 abnormalities), poor performance status (ECOG score ≥2), and serum creatinine >1.3 mg/dL. This study validates the Kantarjian model for progression-free survival (PFS) and overall survival (OS) in older patients with AML treated with intensive chemotherapy. Methods: Adults aged ≥70 years with AML (≥20% blasts in bone marrow or peripheral blood) who received intensive chemotherapy at UPMC Hillman Cancer Center between 2000 and 2011 were evaluated. Patients were stratified into low, intermediate, and high-risk groups according to the Kantarjian (2010) model and analyzed for PFS and OS using the Kaplan-Meier method. Differences in PFS and OS between risk groups were assessed with the log-rank test. ECOG performance status was estimated using historical data at the time of diagnosis. Additional variables, including AML type (primary vs. secondary), percent blasts at diagnosis, percent CD34-positive blasts, hemoglobin, leukocytes, platelets, LDH, AST, ALT, total bilirubin, albumin, and Charlson comorbidity index (CCI) were tested for added prognostic value when incorporated into the model, using Cox proportional-hazards regression for PFS and OS. Results: Clinical data were collected for 68 patients. Of these, 26 patients, all of whom were diagnosed prior to 2003, were excluded from the final analysis due to insufficient electronic health records. The remaining 42 patients were used for the validation study. Median age at diagnosis was 73 years (range: 70-87). Twenty-seven patients (64%) had primary AML, whereas 10 (24%) had AML evolving from another hematologic disorder and 5 (12%) developed AML after radiation or chemotherapy for another malignancy. Eleven (26%) patients had ≥3 karyotypic abnormalities and the remaining 31 (74%) had fewer than 3. Thirty-three (79%) patients had an ECOG performance status of 0 or 1, and the remaining 9 (21%) did not have sufficient historical data to estimate ECOG score and were given a score of 0. In total, there were 23, 16, and 3 patients categorized into the low, intermediate, and high-risk groups, respectively. These groups had non-overlapping PFS and OS curves (p <0.001 for both endpoints). The low, intermediate, and high-risk groups had median PFS of 9.6, 5.1, and 2.1 months and median OS of 14.0, 6.3, and 2.1 months, respectively. None of the additional variables were found to add significant prognostic value to the existing model. Discussion: The Kantarjian (2010) model is a valid method of risk-stratifying older adults with respect to PFS and OS, and may be useful when weighing the risks and benefits of intensive chemotherapy in these patients. In this study, we did not identify other disease characteristics or measures of organ function that significantly improved the model, although our analysis is limited by small sample size. We note that all patients in our study had an ECOG score of 0 or 1, implying selection of healthier patients for induction chemotherapy at our institution. Our results suggest that patients in the intermediate and high-risk groups may not derive significant PFS and OS benefit from intensive chemotherapy when the risks of morbidity and mortality from treatment are considered. Disclosures No relevant conflicts of interest to declare.

scholarly journals Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations

2018 ◽  
Vol 36 (15) ◽  
pp. 1486-1497 ◽  
Author(s):  
Sylvie D. Freeman ◽  
Robert K. Hills ◽  
Paul Virgo ◽  
Naeem Khan ◽  
Steve Couzens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
High Risk Factors ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/− NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.

Gene Expression Profiling Identifies Distinct Subclasses in Core Binding Factor Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 673-673
Author(s):  
Lars Bullinger ◽  
Stephan Kurz ◽  
Konstanze Dohner ◽  
Claudia Scholl ◽  
Stefan Frohling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Patterns ◽  
The Other ◽  
Rank Test ◽  
Core Binding Factor ◽  
Log Rank Test ◽  
Binding Factor ◽  
Acute Myeloid

Abstract Recurrent cytogenetic aberrations have been shown to constitute markers of diagnostic and prognostic value in acute myeloid leukemia (AML). However, even within well-defined cytogenetic AML subgroups with an inv(16) or a t(8;21) we see substantial biological and clinical heterogeneity which is not fully reflected by the current classification system. Therefore, we profiled gene expression in a large series of adult AML patients with core binding factor (CBF) leukemia [inv(16) n=55, t(8;21) n=38] using a whole genome DNA microarray platform in order to better characterize this disease on the molecular level. By unsupervised hierarchical clustering based on 8556 filtered genes we observed that our CBF leukemia samples separated primarily into three different subgroups. While two of the subgroups were characterized by inv(16) and t(8;21) cases, respectively, the third subgroup contained a mixture of both cytogenetic groups. There was no obvious correlation with known secondary aberrations or molecular marker like FLT3-ITD, NRAS and KIT mutations between the cases in the mixed subgroup and the others. However, the newly defined inv(16)/t(8;21)-subgroup (n=35) was characterized by distinct clinical behavior with shorter overall survival times (P=0.029; log rank test) compared to the other two groups. Unsupervised analyses within the inv(16) and t(8;21) cases also revealed corresponding inv(16) and t(8;21) subgroups with a strong trend towards inferior outcome (P=0.11 and P=0.09, respectively; log rank test). Since the primary translocation/inversion events themselves are not sufficient for leukemogenesis, distinct patterns of gene expression found within each of these cytogenetic groups may suggest alternative cooperating mutations and deregulated pathways leading to transformation. Therefore, we performed a supervised analysis to determine the characteristic gene expression patterns underlying the cluster-defined subgroups. We identified 528 genes significantly differentially expressed between the newly defined inv(16)/t(8;21)-subgroup and the other CBF cases (significance analysis of microarrays, false discovery rate &lt; 0.001). Potential candidates for cooperating pathways characterizing the mixed inv(16)/t(8;21)-subgroup included e.g. AVO3, a member of the mTOR pathway, oncogene homologs like LYN and BRAF, as well as FOXO1A and IL6ST which have been previously identified to correlate with outcome in AML (Bullinger et al., N Engl J Med350:1605, 2004). In conclusion, while the observed signatures remain to be validated for their functional relevance, both supervised and unsupervised methods provide numerous insights into the pathogenesis of CBF AML, identifying clinically significant patterns of gene expression, as well as candidate target genes involved in leukemogenesis.

Sequential Chemotherapy Followed By Reduced Intensity Conditioning and Allogeneic Hematopoietic Transplantation For High Risk Acute Myeloid Leukemia Patients In First Complete Remission: A Prospective Pilot Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2162-2162
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Marie Y. Detrait ◽  
Helene Labussiere ◽  
Sandrine Hayette ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Reduced Intensity Conditioning ◽  
Secondary Aml ◽  
Prospective Pilot Study ◽  
First Complete Remission ◽  
Reduced Intensity ◽  
Acute Myeloid

Abstract Advances in chemotherapy have improved the prognosis of patients with acute myeloid leukemia (AML), however, high-risk patients still have a poor outcome. In this category of patients, the only therapeutic strategy with curative potential remains allogeneic hematopoietic stem cell transplantation (allo-HSCT). With the aim to improve the effect of allo-HSCT by sequential use of chemotherapy followed by reduced intensity conditioning (RIC), we conducted a prospective pilot study in high-risk AML patients in first complete remission (CR1). The high-risk population included intermediate II [t(9;11)(p22;q23); MLLT3-MLL, cytogenetic abnormalities not classified as favorable or adverse] and unfavourable patients [inv(3)(q21q26.2) or t(3;3)(q21;q26.2); t(6;9)(p23;q34); t(v;11)(v;q23); MLL rearranged, -5 or del(5q); -7; abnl(17p); complex karyotype] (Dohner et al. Blood 2010), secondary AML, and patients requiring 2 induction courses to obtain CR. The chemotherapy sequential regimen consisted in fludarabine 30 mg/m2, high-dose cytarabine 2 g/m2, and amsacrine 100 mg/m2 from days -12 to -9 (FLAMSA). After 3 days of rest, RIC consisted of 4 Gy total-body irradiation (TBI) on day -5, cyclophosphamide (40 mg/kg with HLA-identical sibling, 60 mg/kg for unrelated or mismatched donors) on days -4 and -3, and rabbit antithymocyte globulin (ATG, Genzyme) (5 mg/kg total dose) from day -3 to day -1. As a new experimental approach, we replaced TBI by iv. busulfan (BU) (Busilvex, Pierre Fabre) 3.2 mg/kg/d during either 4 or 2 days according to patient age (>55 years) (from day -7 to -4 or from day -5 to -4). Peripheral-blood stem cells (PBSC) were preferred; bone marrow (BM) and cord blood (CB) were also accepted. Graft-versus-host disease (GvHD) prophylaxis consisted in ciclosporine from day -1, and mycophenolate mofetil (15 mg/kg bid), starting from day 0. In the absence of GvHD, MMF was discontinued by day+50 and ciclosporine was tapered from day +60 to +90. Except for cord blood transplantation, patients received 3 prophylactic increased doses of donor lymphocyte infusions (DLI) if they were in CR and GvHD-free at day +120 or 30 days after discontinuation of immunosuppressive agents starting at 1x106 CD3+ cells/kg. Between August 2010 and March 2013, 26 consecutive AML patients in CR1 were included; 11 males and 15 females with a median age at allo-HSCT of 55 years (range: 24-67), 19 (73%) were de novo AML and 7 (27%) secondary AML. According to cytogenetics and molecular markers, 22 (85%) were unfavourable and 4 (15%) were in intermediate II category. Before allo-HSCT, to reach CR1, 20 (77%) patients received one induction chemotherapy and 6 (23%) needed 2 inductions. Cell source was PBSC for 23 (88%) patients, CB for 2 and BM for 1 patient. Donors were 10/10 HLA matched siblings in 9 (35%) patients, 10/10 HLA matched unrelated in 8 (31%) patients and HLA mismatched for the rest of patients [unrelated 9/10 (n=7), CB 4/6 (n=2)]. For ABO compatibility, 13 (50%) were compatible, 5 (19%) had minor incompatibility and 8 (31%) had major incompatibility. For conditioning, 6 (23%) patients received TBI, 13 (50%) received 4 days BU and 7 (27%) received 2 days BU. After transplantation, 23 (88%) patients engrafted, 3 patients died early (1 at day 1 and 1 at day 2 both from septic shock; 1 at day 8 from pneumonia and pericardial effusion). At day 90 post-allo-HSCT, 18 (78%) showed total donor chimerism and 5 (22%) had mixed chimerism and all patients were in CR. There were 6/23 (26%) patients with acute GvHD [2 gr I, 2 gr II and 2 gr III] and 5/23 (22%) chronic GvHD [4 limited and 1 extensive], all before DLI. After a median follow-up of 9 months (range: 0.03-35), the 2-years probability of overall survival (OS) for the whole population was 58% (confidence interval: 47-69) (Figure 1a) and the 2 years cumulative incidence of relapse was 18% (confidence interval: 17-19). At the latest follow-up, 16/23 (70%) engrafted patients were alive, 4/23 (17%) patients relapsed and died later and 3/23 (13%) patients died from transplant related infectious complications. No statistical difference in terms of OS and relapse incidence was found between the 3 types of conditioning, (Figure 1b). FLAMSA-RIC regimen followed by allo-HSCT showed promising results in high-risk CR1 AML patients. Because of some early severe infections, an efficient prophylactic anti-infectious strategy is recommended. The use of BU instead of TBI does not impact on transplant outcomes. Disclosures: No relevant conflicts of interest to declare.

Oral Hydroxyurea Before Intensive Chemotherapy For Hyperleucocytic Acute Myeloid Leukemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2657-2657
Author(s):  
Anne-claire Mamez ◽  
Emmanuel Raffoux ◽  
Sylvie Chevret ◽  
Virginie Lemiale ◽  
Nicolas Boissel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Hospital Mortality ◽  
Myeloid Leukemia ◽  
Early Death ◽  
Tumor Burden ◽  
Hospital Death ◽  
Intensive Chemotherapy ◽  
Secondary Aml ◽  
Acute Myeloid

Abstract Aim Acute myeloid leukemia (AML) with high white blood cells count (WBC) is a medical emergency. In these patients, leucostasis, disseminated intravascular coagulation (DIC) and tumor lysis syndrome lead to frequent death before achieving complete remission. Smooth reduction of tumor burden with oral hydroxyurea (HU) has been suggested as an efficient strategy to prevent dramatic clinical worsening induced by frontline intensive chemotherapy but has never been assessed or compared to other strategies. We aimed to evaluate the benefit of administration of HU before intensive chemotherapy in patients with hyperleucocytic AML. Methods We retrospectively reviewed all medical charts of patients admitted to our institution from 1997 to 2011 with newly diagnosis of AML and WBC over 50 G/L excluding promyelocytic AML, patients unfit for intensive induction chemotherapy or with insufficient follow up data. We compared in-hospital mortality (occurring during the hospitalization time or before day 90) and other early outcomes (early death, occurring before day 14, intensive care admission, life’s support therapy) of patients that received HU cytoreduction before chemotherapy versus upfront chemotherapy. Results One hundred and sixty patients were included. Median age was 47 years, median WBC was 120 G/L (interquartile range 82-199), 67% had FAB M4/M5, 11% had secondary AML and 49% had normal karyotype, 35% had FLT3 Internal Tandem Duplication, with no difference between the two groups. 107 patients received HU before chemotherapy initiation with a median dose of 50 mg/kg daily for 4, interquartile range [2-6] days. 56 received emergency induction chemotherapy first (median time after diagnostic 0 [0-1] days). In-hospital death rate was lower for patients treated with HU (19% vs. 34%, p= 0.047). In addition, univariate analysis of in hospital mortality identified the role of preexisting conditions, tumor burden markers and the presence of inaugural complications, as shown in Table 1. As Hydroxyurea was not prospectively randomized, a propensity score was used to adjust the comparison of the 2 groups on other significant prognostic factors and shows that oral hydroxyurea treatment remains significantly associated with a reduction of in-hospital mortality. Monocytic morphology, secondary AML, and year of diagnosis were not predictive of early death. After multivariate analysis, Treatment group (p=0,02), age (p<0.01) and initial WBC (p=0.02) were the 3 remaining factors associated with in-hospital death. DIC was the only parameter associated with death before day 14 in multivariate analysis (p=0,03). Additionally, a non-parametric analysis showed that mortality was linearly related to WBC decline during the 3 first days in HU group. Also, an analysis of HU response (defined by achievement of WBC count below 20 G/L before chemotherapy) reveals that baseline characteristics were insufficient to predict HU sensitivity. Myelotoxicity and WBC decreasing kinetic were similar in both groups. Relapse rate (p=0.85) and one-year event free survival (p=0.87) was not inferior in patients of the HU group achieving complete remission. Finally, patients in the HU group were more likely to be included in a prospective multicenter trial (31% vs. 16% p=0,04) thanks to the longer time available to clinicians and patients to be included. Conclusion This study provides the first systematic review of HU use in hyperleucocytic AML. Oral HU before chemotherapy seems a safe and efficient strategy to reduce early death of these high-risk patients. Also it could help clinicians to include theses patients in prospective treatment trials. These results remain to be confirmed in a randomized trial Disclosures: No relevant conflicts of interest to declare.

scholarly journals Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome:

Cancer ◽  
2006 ◽  
Vol 106 (5) ◽  
pp. 1090-1098 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Jorge Cortes ◽  
Francis Giles ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Acute Myeloid

scholarly journals Minority Health Disparities in Acute Myeloid Leukemia: A Metropolitan, Single-Center Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1987-1987
Author(s):  
Keri R. Maher ◽  
Ian M. Bouligny
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
African American ◽  
African Americans ◽  
Myeloid Leukemia ◽  
Insurance Coverage ◽  
Rank Test ◽  
Log Rank Test ◽  
Disease Biology ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is an aggressive bone marrow cancer affecting 20,000 adults in the United States yearly. Five-year relative survival remains poor at 29.5%, though this has been steadily increasing. There are no known differences in diagnostic rates between racial and ethnic groups. Previous work has shown being African American is an independent predictor of poorer survival - particularly in impoverished areas and those with Medicaid. We aimed to identify potential racial disparities amongst our AML population - with special attention to insurance coverage, access to care, disease biology, regimen selection, toxicities, referral for allogeneic hematopoietic stem cell transplant (alloHSCT), and overall survival with non-Hispanic Whites as a control. Methods: This study is a retrospective analysis of patients diagnosed with AML and treated at Virginia Commonwealth University/Massey Cancer Center identified by our data analytics core from June 2018 to December 2020. Data were extracted and manually verified from the electronic medical record into an AML database instrument created in RedCap. Race was determined by self-report. Statistical analysis was performed using GraphPad Prism. Descriptive and inferential statistics were performed with comparisons between groups using an unpaired t-test with Welch's correction or with Fischer's exact test. Overall survival rates were evaluated using Kaplan-Meier analyses and compared using log-rank test. The event date was death and patients were otherwise censored at the date of last contact. Results: Our cohort consisted of 160 patients: 26.3% African Americans, 68.8% Whites, 1.9% Hispanic/Latinos, 1.9% other or declined to state, and 1.3% were unknown. To analyze the impact of minority populations, Hispanic/Latino and "other" categories were combined with African American into a "Non-White" cohort (N = 48) and compared to the "White" cohort (N = 110). There was no baseline difference in age (p= 0.212), Charleson Comorbidity Index (CCI) at presentation (p = 0.692), or ECOG status (p = 0.920) at presentation (Table 1). Assessment of disease biology, including European Leukemia Network risk stratification (p = 0.507), presence of complex karyotype (p = 0.366) and presence of TP53 mutations (p = 0.776) did not detect a statistically significant difference between the two groups (Table 1). Choice of intensive (vs non-intensive) induction based on physician's discretion was also similar (62.5% in non-White, 68.2% in Caucasians, p = 0.583). Toxicity analysis such as ICU during induction (p = 0.519) and death within 60 days of induction (p = 0.8) showed no difference between groups. In parameters assessing access to care, non-Whites were more likely than Whites to have either Medicaid or no insurance coverage, opposed to private insurance or Medicare (p = 0.0166). Despite this, there was no difference in overall survival assessed by log-rank test (p = 0.068) across all cytogenetic cohorts or with respect to the adverse risk cohort (p = 0.143), though the non-White cohort had a mOS of 286 days (9.4 months) compared to 764 days (25.1 months) in the White cohort. Rates of being lost to follow up were not different between the two groups (p = 0.34). However, rates of alloHSCT were approaching significance with p = 0.0528 favoring Caucasians. Discussion: Our data suggest similar disease biology at presentation amongst racial and ethnic groups, as well as similar comorbidities, performance status at diagnosis, and choice of induction regimen. As previous research has shown, our minority cohort was more likely to have no insurance or Medicaid than the Caucasian population. However, this did not lead to a statistically significant overall survival difference. Rates of alloHSCT were approaching statistical significance between the groups. This suggests that improving access to transplant might be one of the more effective tools for improving outcomes in this group. Additionally, demographics in the Richmond metro area demonstrate a population of 47% African American and 48% Whites, whereas our data showed 26% African Americans and 69% Whites, with no known strong racial predilection of AML based on SEER data (46% vs 54%, respectively). Thus, concern remains that there may be a significant number of patients with AML who either do not seek care, or present in a condition where treatment is no longer possible. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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