Secondary Acute Myeloid Leukemia: Demographic, Physiopathogenic, Clinical and Therapeutic Comparative Study

INTRODUCTION Secondary Acute Myeloid Leukemia (s-AML) evolves from a previous hematopoietic clonal disease such as Myelodysplastic Syndromes (MDS/AML), myeloproliferative neoplasia (NPM/AML), medullary insufficiencies - aplastic anemia - (AA/AML) or exposure to chemo or radiotherapy (t-AML). The objective of this work is to describe and highlight the demographic, pathophysiologic and clinical-therapeutic characteristics of s-AML patients compared with p-AML. METHODS This is a retrospective cohort study based on the casuistry from 34 reference centers in Latin America during a period of 10 years (JAN10'-MAY19'). Patients ≥18 years old with primary AML, excluding the promyelocytic subtype (p-AML), and s-AML were admitted. Age, gender, performance status, comorbidity, cytogenetics, mutations, AML subtypes, extramedullary compromise, treatments and overall survival (OS) were analyzed. Statistically, Graph Pad Prism version 5.00 and, SPSS version 17 were used. RESULTS One thousand eleven patients with newly diagnosed AML were recruited, 693 (68.5%) corresponded to p-AML and 318 (31.5%) to s-AML. The demographic differences between p-AML and s-AML are shown on Table 1. Subtypes of s-AML: t-AML (18.5%), MDS/AML (58.2%), NMP/AML (13.5%), AA/AML (5.7%) and others s-AML (4.1%). Global median age was 58 years (R 18-93) and male 52%. Extramedullary compromise in CNS (3.2%) and other organs (5.5%). Seven hundred ninety-three cytogenetic studies were evaluable (based on MRC classification): High (22.3%), Intermediate (68.3%) and Low Risk (9.3%). FLT3 mutation was more frequently found in p-AML. In s-AML, the multivariate study showed short overall survival associated with ECOG ≥2 (HR:2.0), white blood count ≥ 50x109/L at diagnosis (HR:1.9), poor risk karyotype (HR:1.6) and age over 60 years (HR:1.5). At least, 883 patients received treatment (Table 2). During this study period, 211 patients (21%) were transplanted; 49 (23%) were s-AML; histoidentical related donor (46%), haploidentical (39%), non-related (8%) and autologous (7%). The median survival for all AML was 11.0 months with a statistically significant difference in favor of the p-AML (Figure 1). CONCLUSION Performance status (by ECOG ≥2), age ≥60, level of leukocytes a ≥50x109/L, poor risk karyotype and s-AML subtype at diagnosis had a significant worse impact on overall survival. Most patients with s-AML came from MDS, they were older and their incidence increased as the population aged. They presented more comorbidities and worse performance status. Undoubtedly, our findings showed that s-AML is a distinct high risk subset of myeloid disorder with adverse prognosis and represents a therapeutic challenge. Disclosures No relevant conflicts of interest to declare.

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The FLAG Chemotherapy Regimen Is an Alternative to Anthracycline Based Therapy for the Treatment of Acute Myeloid Leukemia for Patients with Multiple Co-Morbidities or Preexisting Cardiac Disease

Blood ◽

10.1182/blood.v124.21.961.961 ◽

2014 ◽

Vol 124 (21) ◽

pp. 961-961

Author(s):

Lalit Saini ◽

Robert Turner ◽

Loree Larratt ◽

Joseph Brandwein ◽

Marlene Ann Hamilton ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Cardiac Disease ◽

Older Patients ◽

Myeloid Leukemia ◽

Advanced Age ◽

Cell Transplant ◽

Poor Risk ◽

Significant Difference ◽

Acute Myeloid

Abstract BACKGROUND: Anthracycline based treatment for acute myeloid leukemia (AML) can be associated with significant morbidity and mortality amongst older patients or those with significant co-morbidities. Furthermore, for patients with previous anthracycline exposure or preexisting cardiac disease anthracyclines pose an increased risk of cardiotoxicity. For such patients intensive treatment options are limited. The FLAG (fludarabine, cytarabine and filgrastim) regimen is a non-anthracycline based chemotherapy useful for relapsed/refractory AML and as initial therapy for “fit” eligible patients. We present our experience using FLAG as first line therapy in a cohort of newly diagnosed AML patients with advanced age, significant co-morbidities or preexisting cardiac disease. METHODS: A single institution retrospective chart review was undertaken of patients treated with FLAG as frontline therapy from 2004 – 2013 with follow-up until June 2014. All patients were considered ineligible for standard ‘3+7’ treatment by the attending physician. RESULTS: Over the study period 56 patients received FLAG. Due to patient refusal or induction complications bone marrow assessments to ascertain remission status were not performed in 10 patients – to minimize bias these patients were evaluated for toxicity and overall survival (OS) but excluded from complete remission (CR) and relapse free survival (RFS) analysis. Of the 56 patients, 68% were males. The median age was 69 (21 – 80) with 79% aged ≥ 60 and 43% aged ≥ 70. Fifty-five percent (31) of the patients had primary AML and cytogenetics were favorable in 5% (3), intermediate in 66% (37), poor-risk in 21% (12) and failed in 7% (4). Forty-six percent (26) were treated with FLAG due to preexisting cardiac disease and others due to advanced age (20%), poor performance status (16%), co-morbidities (16%) or previous anthracycline exposure (2%). The ages of patients treated with FLAG due to cardiac disease or other reasons was similar (63.5 years vs. 66.9 years, p=0.27). Amongst patients with cardiac disease a pre-chemotherapy cardiac evaluation revealed wall motion abnormalities in 39% and an ejection fraction (EF) ranging from 33% - 81% with a borderline (≤ 50-51%) EF in 46%. Febrile neutropenia was observed in 82% (46) of patients, 27% (15) required intensive care support and the induction mortality was 16% (9). Amongst patients evaluated for a CR (46/56), 48% (22/46) obtained a CR. Although a CR was seen in 100% (3/3), 46% (15/33) and 37% (3/8) of patients with favorable, intermediate and poor-risk cytogenetics respectively there was no statistically significant difference (p=0.22) between groups. A CR was obtained in two additional patients following a second course of FLAG for an overall CR rate of 52% (24/46). Of these 24 patients, 8 (33.3%) received no additional treatment while 16 (66.7%) received consolidative chemotherapy. Of 10 eligible patients, 4 proceeded to an allogeneic stem cell transplant (allo-SCT) including two with preexisting cardiac disease. Of patients not transplanted 50% (10/20) eventually relapsed. There was no difference in relapse rates for those receiving FLAG for age/co-morbidities vs. cardiac disease (60% vs. 40%, p= 0.66) or for patients age <60 vs. ≥ 60 (50% vs. 50%, p=1.0). The median RFS was 441 days with no difference between patients treated with FLAG for cardiac reasons vs. other reasons (p=0.33) or for patient’s age < 60 vs. ≥ 60 (p=0.66). The median OS for the 56 patients was 278 days with 1 and 2 year survivals of 44% and 22% respectively. The median OS for patient’s age < 60 was higher than those age ≥ 60 (1102 days vs. 218 days, p=0.009) but there was no difference in the OS between patients treated with FLAG for cardiac disease and those treated for other reasons (305 days vs. 254 days, p=0.202). The median survival of patients with favorable, intermediate and unfavorable risk cytogenetics was 523 days, 311 days and 87 days respectively but this was not statistically significant (p=0.25) likely due to limited patient numbers. Conclusions: The FLAG regimen is a non-anthracycline based regimen that may serve as an alternative to the standard ‘3+7’ induction for AML in older adults or those with significant co-morbidities including preexisting cardiac disease. It is associated with comparable remission rates and overall survival in older patients. In addition, it may allow some patients with preexisting cardiac disease to proceed to allo-SCT. Disclosures No relevant conflicts of interest to declare.

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Acute Myeloid Leukemia Induction with Cladribine: Effects of Age and Leukemia Risk

Blood ◽

10.1182/blood.v128.22.3988.3988 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3988-3988 ◽

Cited By ~ 1

Author(s):

Martin W. Schoen ◽

Susan K. Woelich ◽

James T. Braun ◽

Mark J. Fesler ◽

Paul J. Petruska ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Complete Response ◽

Intermediate Risk ◽

Poor Risk ◽

One Year ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7+3). Co-administration of cladribine may increase efficacy of cytarabine. This rationale directed Saint Louis University (SLU) to adopt a regimen derived from the Polish Adult Leukemia Group (Holowiecki, JCO 2012) which adds five days of cladribine to idarubicin based 7+3 (IAC). We report the SLU experience with toxicity and survival following IAC induction. Additionally, we discuss the effects of IAC in patients 60 and older as an area of particular interest. Methods: Retrospective analysis of patients with newly diagnosed AML (APL excluded) and high-risk MDS who received IAC from January 2009 to September 2015. IAC was initiated as cytarabine 200mg/m2 by continuous infusion for seven days, idarubicin 12mg/m2 daily for three days, and cladribine 5mg/m2 for five days. Mortality and disease response were analyzed, with stratification by age and NCCN leukemia risk classification. Results: Of 107 patients, 57 patients (53%) were age 60 and older. By NCCN cytogenetic and molecular stratification, 21 (20%) had favorable risk; 43 (40%) intermediate risk; and 43 (40%) poor risk leukemia. Complete response (CR) occurred in 75 (70%) patients and CRi in an additional 9 patients (8%) for an overall response rate of 79% (see Table 1). At one year, 58% of patients were still alive with 47% (27/57) of patients ≥60 years and 72% (36/50) of those <60 years surviving (OR 2.8, 95% CI 1.3-6.4). When stratifying by NCCN risk, no deaths at one year occurred among the favorable risk group (0/21), but 16/43 (37%) and 28/43 (65%) occurred in intermediate and poor-risk strata, respectively (p<0.001 by chi-squared). Median overall survival was 17.2 months with mean follow-up of 32.8 months. Cox proportional hazard ratio (HR) for death were significant for age ≥60 compared to age <60 (HR 2.2, 95% CI 1.3-3.7). Additionally, HR for intermediate risk leukemia was 6.2 (95% CI 1.8-21) and for poor risk leukemia it was 11 (95% CI 3.4-36), when each were compared to favorable risk. Thirty-three (31%) of patients were known to have received an allogeneic transplant, of which 42% (14/33) were 60 and older. Adverse events: Overall, the treatment related mortality (TRM) (defined as death within the first 28 days) was 11%. Eleven of 12 TRM events occurred in patients ≥60 years (OR 12, 95% CI 1.5-94). Diarrhea occurred in 71% of patients with 46% enduring mucositis. Intensive care unit admission occurred in 23% overall, and infections were documented in 73% of patients. Most common infectious etiology was coagulase negative staph in 29% (23/78). For patients surviving to discharge (90/107), median hospitalization was 30 days post induction. Conclusions: Cladribine combined with cytarabine and idarubicin is an effective induction regimen for AML with high rates of CR, even in patients 60 and older. Our data show that NCCN leukemia risk is a better predictor of survival compared to age and that patients aged ≥60 years have better survival (lower HR for death) compared to those with intermediate or poor risk leukemia. Additionally, CR and 1 year overall survival with IAC are better than expected in the older cohort, however, TRM is elevated among those 60 and older. Higher intensity regimens in older patients may be justified in select patients, especially given the greater life expectancies enjoyed in the modern era. Several ongoing prospective trials investigating the safety and efficacy of cladribine in older patients will provide additional information to inform the use of IAC in older patients. Table 1 Table 1. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211036592 ◽

2021 ◽

Vol 8 ◽

pp. 204993612110365

Author(s):

Kundan Mishra ◽

Suman Kumar ◽

Sandeep Ninawe ◽

Rajat Bahl ◽

Ashok Meshram ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Febrile Neutropenia ◽

Burkholderia Cepacia ◽

Myeloid Leukemia ◽

Tertiary Care ◽

Care Hospital ◽

Significant Difference ◽

The Mean ◽

Acute Myeloid

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients.

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CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2017.77.6112 ◽

2018 ◽

Vol 36 (26) ◽

pp. 2684-2692 ◽

Cited By ~ 248

Author(s):

Jeffrey E. Lancet ◽

Geoffrey L. Uy ◽

Jorge E. Cortes ◽

Laura F. Newell ◽

Tara L. Lin ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Remission Rate ◽

Phase Iii ◽

Newly Diagnosed ◽

Secondary Acute Myeloid Leukemia ◽

Acute Myeloid

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

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Variations in Proteasome Enzymatic Activities in Plasma of Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome and Their Value in Predicting Clinical Behavior.

Blood ◽

10.1182/blood.v108.11.4497.4497 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4497-4497 ◽

Cited By ~ 1

Author(s):

Wanlong Ma ◽

Francis Giles ◽

Susan O’Brien ◽

Iman Jilani ◽

Xi Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Performance Status ◽

Proteasome Inhibitors ◽

Leukemic Cells ◽

Clinical Behavior ◽

Cytogenetic Abnormalities ◽

Significant Difference ◽

And Performance ◽

Acute Myeloid

Abstract The ubiquitin-proteasome pathway is responsible for multiple pathways in cancer cells; proteasome inhibition causes rapid apoptosis of tumor cells. Three different types of peptidase activities have been reported for proteasomes: chymotrypsin-like (Ch-L), trypsin-like (Tr-L), and caspase-like (Cas-L) (postglutamyl peptide hydrolytic-like). Various proteasome inhibitors affect each of the 3 activities differently and at different concentrations. For example, NPI-0052 inhibits Ch-L and Tr-L activities at lower concentrations than does bortezomib, while bortezomib inhibits Cas-L at lower concentrations than does NPI-0052. These enzymatic activities are usually measured in normal or tumor cells to monitor therapy with proteasome inhibitors. Because rapidly proliferating leukemic cells pour their proteins, DNA, and RNA into the circulation, we developed fluorogenic kinetic assays using peripheral blood plasma. The assays used peptide-AMC (7-amino 4-methylcoumoran) substrates to measure Ch-L, Tr-L, and Cas-L activities. We measured proteasome activities in plasma from 188 patients with acute myeloid leukemia (AML) and 58 patients with myelodysplastic syndrome (MDS) and assessed their correlations with clinical behavior. Significantly (P < 0.001) higher Ch-L, Tr-L, and Cas-L activities were seen in AML patients (medians: 1.39, 1.51, and 2.40 pmol AMC/sec/mL, respectively) and MDS patients (medians: 1.16, 1.40, and 1.67 pmol AMC/sec/mL, respectively) than in healthy volunteers (n=42) (medians: 0.80, 0.74, and 0.81 pmol AMC/sec/mL, respectively). The difference in Cas-L activity between AML and MDS was significant (P <0.001). While there was no significant difference between Ch-L and Cas-L activities in healthy controls, there was a significant difference between the 2 activities in both AML and MDS. Cas-L and Ch-L, but not Tr-L, correlated with WBC count and lactic dehydrogenase in AML and MDS patients. In AML patients, higher levels of Ch-L and Cas-L were associated with poor response to a variety of therapies (P = 0.004 and P = 0.001, respectively). Cas-L correlated strongly with survival in AML patients when used as an activity-dependent variable (P <0.001) or when the median was used as a cut-off (P = 0.004). This was independent of cytogenetic abnormalities, age, and performance status. Patients with intermediate-risk cytogenetic abnormalities and Cas-L activity >3 pmol AMC/sec/mL had significantly shorter survival (P = 0.04). Ch-L activity was also predictive of survival in AML independent of age and cytogenetic and performance status, but not independent of Cas-L. In MDS, higher levels of Cas-L, but not Ch-L, correlated with shorter survival and this was independent of cytogenetic abnormalities. The increased cell-free circulating proteasome activities most likely reflect the leukemic cells and may be a marker not only for disease, but also potentially for monitoring therapy. These data also suggest that patients with AML may benefit differentially from proteasome inhibitors depending on the specific therapeutic effect of the inhibitor.

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Validation of Monosomal Karyotype Based Model In the Risk Stratification of Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v116.21.2745.2745 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2745-2745

Author(s):

Murtadha K. Al-Khabori ◽

Karen Yee ◽

Vikas Gupta ◽

Aaron Schimmer ◽

Andre Schuh ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Risk Stratification ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Structural Abnormality ◽

Complex Karyotype ◽

Poor Risk ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 2745 Background: The influence of cytogenetic abnormalities on the prognosis of acute myeloid leukemia (AML) has been well-documented; however, the relative impact of certain miscellaneous abnormalities remains controversial. Recently, monosomal karyotype-based risk stratification has been shown to further discriminate the prognosis within the poor-risk karyotype group (Breems et al. JCO 2008), but this finding requires further validation. Methods: We retrospectively reviewed 779 consecutive adult AML patients treated with standard induction chemotherapy, consisting of daunorubicin plus cytarabine (3+7), at our institution from 1998–2008. After excluding patients with favourable risk, normal, missing or failed karyotype, 290 patients remained and were included in the analysis. Results: The baseline characteristics of these 290 patients were as follows: median age 59 y (range 18–81), male 181, prior malignancy 110, median white cell count (WBC) 7.6 × 10^9/L (range 0–246). The karyotypic features included single monosomy in 42, 2 or more monosomies in 51, and non-monosomy structural and numerical abnormalities in 197 patients. Of the 290, 116 (40 %) had three or more abnormalities (complex karyotype, CK). A total of 141 patients (49 %) achieved complete remission (CR) with 3+7 induction chemotherapy. Sixty-four patients received allogeneic stem cell transplantation in CR. The median overall survival (OS) for all patients was 12 months (95% CI: 10–14 months). The median OS was 10 (95% CI: 6–18), 7 (95% CI: 6–10) and 14 months (95% CI: 12–16) in the single monosomy, 2+ monosomy and non-monosomy groups, respectively (p < 0.0001 by log-rank test comparing the three groups). Among the patients containing at least one monosomy, the OS was not significantly different between the CK and non-CK groups (p = 0.08 by log rank). Similarly, in the non-monosomy structural abnormality group, the OS was not significantly different between the CK and non-CK groups (p = 0.2). Conclusions: Our results provide validation for the monosomal karyotype-based risk stratification for AML, indicating that patients with at least one monosomy have an inferior OS compared to other poor-risk non-monosomy groups. Within each of the monosomy and non-monosomy groups, the presence of a complex karyotype does not significantly influence the OS. Disclosures: No relevant conflicts of interest to declare.

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A Prognostic Score of Overall Survival In Adults with Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v116.21.2730.2730 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2730-2730

Author(s):

Murtadha K. Al-Khabori ◽

Gordon Guyatt ◽

Mark D. Minden ◽

Karen Yee ◽

Vikas Gupta ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Score ◽

Performance Status ◽

Intermediate Risk ◽

Good Discrimination ◽

Prior Malignancy ◽

Acute Myeloid ◽

Deviance Residuals

Abstract Abstract 2730 Background: Acute myeloid leukemia (AML) is a malignant myeloid disorder with heterogeneous outcomes. A number of factors have been shown to be prognostic; age, white blood cell (WBC), prior malignancy, performance status (Eastern Cooperative Oncology Group; ECOG) and cytogenetics. Methods: We planned to develop and validate a prognostic score for the 5-year (y) overall survival (OS) of adults with AML receiving intensive induction chemotherapy. We used Cox model to estimate the regression coefficients and Kaplan-Meier to estimate the 5-y OS. We used Cox-Snell, Schoenfeld and deviance residuals for model diagnostics and bootstrap validation to estimate the performance measures; Harrell's concordance and deviance residuals. Results: We retrospectively analyzed 779 patients treated between 1998–2008, using a prospectively collected database. The median age was 58 y. Most patients had intermediate risk cytogenetics (61%) and good performance status (ECOG 0–1: 79%). The median follow up for the surviving patients was 26.7 months (95% CI 18.8–32.9 months). The 5-y OS was 26% (22- 30%). All variables were statistically significant in the multivariable Cox regression model; age (y) (Hazard Ratio, HR 1.02; 95% CI 1.018–1.034), WBC (1*10^9/L) (HR 1.004; 1.002–1.006), prior malignancy (HR 1.58; 1.26–2.00), ECOG (ECOG 2 HR 1.41; 1.06–1.88, ECOG 3–4 HR 9.99; 4.72–21.18) and cytogenetics (intermediate risk HR 2.49; 1.41–4.39, poor risk HR 4.74; 2.65–8.50). The score divided patients into four risk groups; good (n=47), intermediate (n=129), poor (n=198) and extremely poor (n=87). The estimated 5-y OS was 0.70 (95% CI: 0.53–0.81), 0.37 (0.28–0.46), 0.15 (0.10–0.21) and 0.03 (0.01–0.10) respectively. The model showed good discrimination with large differences between survival curves and good Harrell concordance of 0.69. It showed good calibration using Cox-Snell and deviance residuals. In the intermediate risk cytogenetic group, the model showed good discrimination with over 45% difference in 5-y OS between the good and extremely poor groups. Conclusions: Our study confirmed the prognostic impact of the 5 variables reported in the literature. Using these factors, we developed a score to predict long term OS that showed good discrimination and calibration. The score added further discrimination in the intermediate risk cytogenetic group. Prospective external validation of the score is needed. Disclosures: No relevant conflicts of interest to declare.

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Fludarabine, Cytarabine, and Attenuated-Dose Idarubicin (m-FLAI) Induction for Elderly Patients with Acute Myeloid Leukemia: Results of a Multicenter Phase II Study,

Blood ◽

10.1182/blood.v118.21.3626.3626 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3626-3626

Author(s):

Yoojoo Lim ◽

Youngil Koh ◽

Sung-Soo Yoon ◽

Seonyang Park ◽

Byoung Kook Kim ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Phase Ii ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Performance Status ◽

Free Survival ◽

Induction Regimen ◽

Acute Myeloid

Abstract Abstract 3626 Introduction: Although there have been remarkable improvements in treatment of acute myeloid leukemia (AML), the prognosis of AML in elderly patients remains poor, and the best induction chemotherapy for these patients remains yet unknown. To devise an effective induction regimen for elderly patients with AML, we conducted a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in these patients. Patients and Methods: Elderly (60 years or older) AML patients who did not receive previous chemotherapy were enrolled. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen was comprised of fludarabine (25mg/m2, days 1–4), cytarabine (1000mg/m2, days 1–4), and attenuated-dose idarubicin (5mg/m2, days 1–3). The primary end point was complete remission (CR) rate. Results: A total of 108 patients (median age 68.4 years, M:F=64:44) were enrolled. CR was achieved in 62.9% of patients, and treatment-related mortality rate (TRM) was 25.8%. Median overall survival (OS) was 9.3 months, and median event-free survival (EFS) was 6.6 months. The mortality at 30 and 60 days was 18% and 24%, respectively. Performance status and comorbidity did not have prognostic value in these patients. Bone marrow expression of CD117 was related to long EFS and OS. Conclusion: In conclusion, m-FLAI is a safe and effective induction regimen for previously untreated AML in elderly patients. Bone marrow CD117 expression is an independent good prognostic factor in these patients. (ClinicalTrials.gov number, NCT01247493) Disclosures: No relevant conflicts of interest to declare.

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Patients with Monosomal Karyotype in Acute Myeloid Leukemia Is Prognostically Worse Than with Complex Karyotype

Blood ◽

10.1182/blood.v118.21.4735.4735 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4735-4735

Author(s):

Liu Xiaoli ◽

Xu Na ◽

DU Qingfeng ◽

Xu Dan ◽

Meng Fanyi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Confidence Interval ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Structural Abnormality ◽

Complex Karyotype ◽

Significant Difference ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Abstract 4735 Purpose: Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. To analyze the prognosis of cytogenetic components of a complex karyotype or Monosomal Karyotype in acute myeloid leukemia (AML) except acute promyelocytic leukemia(APL). Patients and Methods:Cytogenetics and overall survival (OS), Disease free survival(DFS) were analyzed in 551 AML patients age 14 to 60 years in our center.Results: There ware 235 patiets with cytogenetic abnormalities, 25 cases with inv(16)(p13.1q22) or t(16;16)(p13.1;q22),and 63 cases with t(8;21); 31 cases (13.2%)met the criteria for MK and 39 cases (16.6%) had a complex karyotype without monosomies. OS was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P<0.01;HR 1.85,95% confidence interval(95%CI),0.95-2.81). There was no difference between MK cases with complex karyotype cases in DFS (P>0.05□GHR 3.42,95% confidence interval(95%CI),2.96-6.70). There was significant difference in regardless of whether OS or DFS between MK+ patients with MK− patients (P<0.01). Conclusion: MK was one of independent risk factor in AML patients. Disclosures: No relevant conflicts of interest to declare.

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Expression of CD56 Is an Independent Prognostic Factor to Predict Relapse in Acute Myeloid Leukemia with t(8;21): Results of Japan Adult Leukemia Study Group (JALSG) AML97 Protocol.

Blood ◽

10.1182/blood.v120.21.2511.2511 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2511-2511

Author(s):

Noriyoshi Iriyama ◽

Yoshihiro Hatta ◽

Jin Takeuchi ◽

Yoshiaki Ogawa ◽

Shigeki Ohtake ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Performance Status ◽

Univariate Analysis ◽

Rank Test ◽

Hematopoietic Stem ◽

Wbc Count ◽

Adverse Factor ◽

Acute Myeloid

Abstract Abstract 2511 Background: Although prognosis of acute myeloid leukemia (AML) with t(8;21) is better than other types of AML, outcome of the patients has not been satisfied. Previously, aberrant antigen expression has been reported as risk factor for AML with t(8;21). However, in the reported series, number of cases was not large enough and chemotherapy regimens were variable. We investigated the association of prognosis and several biomarkers including immunophenotype, WBC count, age, and performance status for large number of AML patients with t(8;21) uniformly treated in JALSG AML97 regimen. Patients and Methods: Seven hundred eighty-nine eligible AML patients were evaluated for the multicenter JALSG AML97 study. Adult patients with de novo AML except for APL, ages 15–64 years, were registered consecutively from 103 institutions that participated in JALSG from December 1997 to July 2001. One hundred forty-four patients with AML with t(8;21) were analyzed in this study with a median 1205 days of observation term from diagnosis. Complete remission (CR), relapse-free survival (RFS), and overall survival (OS) rates were analyzed by Fisher's exact test and log-rank test. Factors that would affect clinical outcome were analyzed by multivariate Cox proportional hazard regression model. Results: AML with t(8;21) frequently expressed CD19, CD34, and CD56 compared to other subtypes of AML. CD11b was rarely expressed. Expression of CD19 favorably affected on CR rate (96% in CD19 positive and 87% in negative patients, p<0.05). Univariate analysis showed WBC>20×109/L, CD19 negativity, and CD56 positivity were adverse factors for RFS. CD56 expression was the only independent adverse factor for RFS by multivariate analysis (73.7% in CD56 negative and 48.2% in CD56 positive patients at 3 yrs) although its expression did not affect on OS. There was no difference of age, sex, WBC count, presence or absence of Auer rod, performance status, or CD15 expression between CD56 positive and negative cases. Expression of CD19 was more common in CD56 negative patients (50% in CD56 negative and 30.6% in CD56 positive patients, p<0.05). Conclusions: We demonstrated that the expression of CD56 was a distinctive adverse factor in a large number of AML patients with t(8;21) treated with JALSG AML97 regimen. CD56 positive AML patients with t(8;21) are possible candidates for hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

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