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

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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Combination of Sorafenib and 5-Azacytidine in Older Patients with Untreated Acute Myeloid Leukemia with FLT3-ITDmutation

Blood ◽

10.1182/blood.v128.22.1611.1611 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1611-1611 ◽

Cited By ~ 3

Author(s):

Maro Ohanian ◽

Guillermo Garcia-Manero ◽

Elias J. Jabbour ◽

Naval Daver ◽

Gautam Borthakur ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Research Funding ◽

Median Overall Survival ◽

Cell Transplant ◽

Overall Response ◽

Grade 3 ◽

Acute Myeloid

Abstract Background: The combination of 5-azacytidine (AZA) and sorafenib has been reported to be a safe and effective strategy in patients with relapsed and/or refractory FLT3-ITD mutated acute myeloid leukemia (AML). We hypothesized that combining sorafenib with AZA, may be used effectively in older patients with untreated AML whose leukemic cells harbor the mutation. Methods: Patients were eligible if they had untreated AML with a FLT3-ITD clone detectable by polymerase chain reaction (at least 10% mutation burden), were 60 years of age or older, and had adequate performance status (ECOG ≤ 2) and organ function. The treatment regimen included AZA 75 mg/m2daily for 7 days combined with sorafenib 400 mg twice daily for 28 days. Cycles were repeated approximately every 4 to 5 weeks. Dose adjustments of both agents, and delay of AZA, based on toxicity were allowed. Results: Overall, 23 patients with untreated AML with a median age of 74 yrs (range, 61-86 yrs) were enrolled. They included 14 (61%) patients with normal cytogenetics, 2 (9%) with complex karyotype, 4 (17%) with other miscellaneous abnormalities, and 3 (13%) with insufficient metaphases. Prior to the initiation of treatment, FLT3-ITD was detected in all patients with a median allelic ratio of 0.35 (range, 0.01-0.89). The overall response rate in 22 evaluable patients was (77%) including 7 (32%) with CR, 9 (41%) CRi/CRp, and 1 (5%) PR. Patients have received a median of 3 (range, 1-35) treatment cycles with the median number of cycles to response being 2 (range, 1-5) and the median time to achieve response, 1.9 months (range, 0.7-4.3 months). The median duration of CR/CRp/CRi is 14.5 months (range, 1.2-28.7 months). Two (9%) patients have proceeded to allogeneic stem cell transplant. With a median follow-up of 4.2 months (range, 0.9-61.4), 8 patients remain alive, 7 still in remission (CR/CRP/CRi). The median overall survival for the entire group is 8.8 months, and 9.2 months in the 17 responding patients (Figure 1). Treatment-related grade 3/4 adverse events included: grade 3 diarrhea (n=2), grade 3 pneumonitis (n=3), grade 4 sepsis (n=2), grade 3 infections (n=3). When patients treated with AZA + sorafenib (n=23) were compared to a matched cohort of historical patients older than 60 years who were treated with hypomethylator-based therapy without sorafenib (n=20), overall response rates (including CR, CRp, CRi, and PR) were statistically similar (77% vs.31%, respectively; p=0.6). The median overall survival for the two groups were 8.8 months and 9.4 months (p=0.67), respectively. The remission duration for the responding patients treated with AZA+sorafenib was significantly longer (16 months) than those on other hypomethylator-based regimens without sorafenib (3.8 months)(p=0.008) (Figure 2). Conclusions: The combination of AZA and Sorafenib is effective and well tolerated in older patients with untreated FLT3-ITD mutated AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Daver:Pfizer: Consultancy, Research Funding; Kiromic: Research Funding; BMS: Research Funding; Karyopharm: Honoraria, Research Funding; Otsuka: Consultancy, Honoraria; Sunesis: Consultancy, Research Funding; Ariad: Research Funding. Burger:Roche: Other: Travel, Accommodations, Expenses; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Gilead: Research Funding; Portola: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

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Impact of Choice of Induction Regimen on Overall Survival and Post-Remission Survival Among Older Adults with Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2021-151422 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2329-2329

Author(s):

Kelli McCrum ◽

Justin LaPorte ◽

Asad Bashey ◽

Scott R. Solomon ◽

Lawrence E Morris ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Older Patients ◽

Myeloid Leukemia ◽

Research Funding ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Induction Regimen ◽

Acute Myeloid

Abstract Older patients make up the majority of those diagnosed with acute myeloid leukemia (AML), however, many of these patients are not able to tolerate intense induction chemotherapy regimens. The use of lower intensity induction such as hypomethylating agents (HMA) with or without venetoclax or other targeted therapies has widened the scope of patients who are able to receive induction chemotherapy and move towards a hematopoietic stem cell transplant. Recent data from the Center of International Blood and Marrow Transplant research showed that patients aging >64 years accounted for 26% of all allogeneic transplantations in 2019 compared to only 9% in 2009. We have previously published a report showing that induction with FLAG +/- Idarubicin (FLAG+ IDA) results in better post remission survival than '7+3'induction (Solh et al, Leuk res 2020). In order to determine how induction chemotherapy affects post-remission outcomes among older patients with AML, 289 patients over the age of 55 year who received either FLAG±IDA, 7+3, or HMA based induction at a single institution were analyzed. Median follow up was 48 months. Patient and disease characteristics were as follows: Median age 64 (55,83) years, secondary AML (10%), abnormal cytogenetics (49%), and NCCN non-favorable risk (76%). Induction regimens included FLAG+/- Ida (n=208, 72%), 7+3 (n=60, 21%) and HMA based (n=21, 7%). A total of 248 patients (86%) achieved CR/Cri after induction with a median time from induction to CR of 28 days. Patients who received induction with FLAG±IDA reached a higher rate of CR after one cycle (92% vs 75% vs 62%) and had a shorter time to CR (27 vs 33vs 55 days) compared to '7+3' or HMA based therapy (p<0.001 for both). FLAG±IDA had better overall survival and DFS 3 years post-remission compared to '7+3' and HMA OS (50%, 45%, 22%, p=0.021) and DFS (45%, 37%, 8% p=0.01) respectively. A total of 133 patients received allogeneic transplantation. Transplant rate was similar between FLAG+/- IDA (n=100) and 7+3 (n=29) at 48% and was significantly better than HMA-based induction 19% (n=4) (p=0.03). Post-transplant survival and DFS was not significantly different between FLAG+/-Ida and 7+3, however both were better compared to HMA based induction with OS (54%, 44%, 25%) and DFS (51%, 44%, 25%) . On multivariate analysis on post remission survival and disease free survival, NCCN risk and age were both associated with OS ( high risk NCCN vs others HR 3.63, P<0.001; Age per 5 year increment HR 1.16, p=0.049) and NCCN risk was the only factor associated with worse DFS ( high vs others HR 2.4, p<0.0001). The choice of induction regimen did not significantly impact post-remission survival outcomes. In conclusion, Older patients with AML achieve higher rates of complete remission, shorter time to remission and better post-remission survival with FLAG+/-IDA than 7+3 or HMA-based induction. Disclosures Solh: BMS: Consultancy; Partner Therapeutics: Research Funding; Jazz Pharmaceuticals: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.

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Clinical Implications of Acute Myeloid Leukemia Presenting as Granulocytic Sarcoma

Blood ◽

10.1182/blood.v116.21.2155.2155 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2155-2155

Author(s):

Batia Ronit Avni ◽

Deborah Rund ◽

Moshe Levin ◽

Sigal Grisaro ◽

Dina Ben-Yehuda ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Medical Center ◽

Granulocytic Sarcoma ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Risk Of Death ◽

Significant Difference ◽

Acute Myeloid

Abstract Abstract 2155 Introduction: Granulocytic sarcoma (GS), also known as chloroma, is described as an extramedullary tumor composed of immature myeloid cells. It has been reported to develop in 2–8% of patients with acute myeloid leukemia (AML) and can occur prior to, concomitantly with, or following the diagnosis of AML. Rarely patients present with GS as an isolated mass without evidence of AML (Byrd JC, J Clin Oncol. 1997). Due to the rarity of this disorder, large series of patients are seldom reported and the prognosis and optimal treatment of patients presenting with GS are not clear. Objectives: In this retrospective study we analyzed the presenting characteristics, treatments and overall survival of all patients presenting with isolated granulocytic sarcoma (GS) or GS with concomitant acute myeloid leukemia (AML) at presentation and compared them to all AML patients, treated at our institution during the same period. Methods: We identified cases who were diagnosed as having GS (with or without bone marrow involvement by AML) and cases of AML (without evidence GS at diagnosis) using ICD-9 codes in the hospitalization data base of the Hadassah Medical Center between 1990 and 2005. We excluded patients with GS at the time of relapse. All GS cases were biopsy-proven. Results: The study population consisted of 19 GS and 235 AML non-GS patients. The median age of these patients was 41 and 48 years, respectively. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission (CR), number of cycles of chemotherapy needed to achieve CR and rate of first relapse. Hematopoietic stem cell transplant (HSCT) (either autologous or allogeneic) was performed in 10 of 19 patients (52.6%) in the GS group and in 66 of 235 (28.1%) in the AML group (p=0.025). The overall survival in the GS group (median 16 months) was not significantly different (p= 0.60) from the AML group. The median time to death in subjects who had radiotherapy (6/19) was identical (median 21 months, p=0.79) to that of subjects who did not receive radiotherapy. Transplantation was associated with prolonged survival in both GS and AML groups (p=0.018 and p<0.0001 respectively). At the end of the follow up, 4 patients in the GS group who underwent HSCT were alive, compared to none in the group who did not undergo HSCT. Karyotype was found to be a prognostic factor in both the GS and AML groups (p=0.0034 and p<0.0001 respectively). In a multivariate analysis there was no statistically significant difference in the risk of death between subjects in the AML and the GS group; hazard ratio (HR) = 0.83, 95% CI (0.456-1.516), p=0.55, after controlling for age, karyotype and transplantation. As expected, in the model, age less than 47.5 years (HR=0.646 (p=0.0022)) and favorable and intermediate karyotype (HR=0.13 (p<0.0001) and HR=0.44 (p<0.0001) respectively, compared to unfavorable) were associated with a lower risk of death. Subjects who did not undergo transplantation had an increased risk of death compared with subjects who underwent the procedure (HR=1.88, p=0.0023) (Fig. 1). Conclusions: To the best of our knowledge this is the first retrospective series of GS patients with concomitant AML at diagnosis compared to all other AML patients in one medical center. The addition of radiotherapy as a treatment modality for GS patients did not appear to change survival. Patients with GS at diagnosis might benefit from upfront aggressive treatment with HSCT. Due to the rarity of this disorder and the remaining open questions, a prospective multi-center study is necessary to address these issues. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood-2019-125311 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5096-5096

Author(s):

Roberto Ovilla ◽

Renee Leonor Crisp ◽

Pamela E Baez-Islas ◽

Jorge A Arbelbide ◽

Sofia Grille ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Performance Status ◽

White Blood Count ◽

Poor Risk ◽

Secondary Acute Myeloid Leukemia ◽

Significant Difference ◽

Acute Myeloid

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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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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Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽

10.1182/blood-2011-06-357764 ◽

2011 ◽

Vol 118 (15) ◽

pp. 4188-4198 ◽

Cited By ~ 40

Author(s):

Sebastian Schwind ◽

Guido Marcucci ◽

Jessica Kohlschmidt ◽

Michael D. Radmacher ◽

Krzysztof Mrózek ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Hox Genes ◽

De Novo ◽

Prognostic Significance ◽

The Impact ◽

Favorable Group ◽

Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

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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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