Treatment With Leukapheresis In Patients Diagnosed With Hyperleukocytic Acute Myeloid Leukemia

Abstract Background Patients with hyperleukocytic acute myeloid leukemia (AML) have a high mortality rate during induction treatment. This mortality is mainly due to bleeding complications, tumor lysis syndrome and symptoms of hyperleukocitosis. Although there is no clear evidence of benefit, leukapheresis is indicated to reduce the number of leukocytes (WBC) in peripheral blood and prevent or relieve leukostasis symptoms before starting cytotoxic therapy. Objetives Analyze the characteristics of a series of patients with hyperleukocytic AML who started induction treatment and assess the outcome depending on whether leukapheresis was performed or not. Methods All adult patients with hyperleukocytic AML (WBC> 95 x 109 / L) who received induction therapy in the Hospital La Fe between 1979 and 2012 were included. The leukapheresis was indicated according to physician discretion. The characteristics and mortality of both groups, patients who underwent leukapheresis and non-leukapheresis, were compared. Then a “matched-paired analysis” was performed according to ECOG, WBC and coagulopathy in a 2:1 ratio to compare results from two homogeneous cohorts. Results One hundred and forty patients diagnosed with hyperleukocytic AML received induction therapy, 18 of them underwent leukapheresis. Patients who underwent leukapheresis compared with non-leukapheresis showed a median age of 55 years (16-71) vs 58 (14-75) and WBC at diagnosis of 198 ´ 109 / L (101-620) vs 141 (97-375), respectively. The leukapheresis group had a worse ECOG (p = 0.03), more leukocytes (p = .003), more coagulopathy (p = .03), more leukostasis symptoms (p <.001) and more mortality at 7 days (p = .02). From the “matched-paired analysis”, 2 cohorts were obtained, whose characteristics are shown in Table 1. After comparing the group of leukapheresis and non-leukapheresis (n = 36), there were no significant differences between them, including leukocyte count, ECOG, coagulopathy and leukostasis. There were also no significant differences in mortality at 7, 14, 21 and 28 days (p = .60, p = .99, p = .92, p = .99, respectively). Conclusions Patients diagnosed with hyperleukocytic AML who underwent leukapheresis showed more leukocytes, leukostasis and coagulopathy. After analizying two comparable groups, leukapheresis failed to reduce mortality. Disclosures: No relevant conflicts of interest to declare.

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The Use of Purine Analogues Does Not Aggravate Infectious Complications During Induction and Consolidation Therapy of Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v114.22.1011.1011 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1011-1011

Author(s):

Marek Seweryn ◽

Jerzy Wojnar ◽

Dariusz Kata ◽

Slawomira Kyrcz-Krzemien

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Infectious Complications ◽

Induction Treatment ◽

High Dose ◽

Consolidation Therapy ◽

Purine Analogues ◽

Acute Myeloid

Abstract Abstract 1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.

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ABCB1 Expression in Acute Myeloid Leukemia (AML): A Possible Predictive Value for Treatment Resistance?

Blood ◽

10.1182/blood.v124.21.3618.3618 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3618-3618

Author(s):

Stephany Corrêa ◽

Eliana Abdelhay ◽

Peter Paschka ◽

Verena I. Gaidzik ◽

Rocio Hassan ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Induction Treatment ◽

Mrna Levels ◽

Complex Karyotype ◽

Hematopoietic Stem ◽

Expression Levels ◽

The Impact ◽

Acute Myeloid

Abstract Introduction: Over the last years, there has been a tremendous increase in understanding acute myeloid leukemia (AML) biology and a great effort has been taken in order to improve AML chemotherapy strategies. However, the growing knowledge of leukemia associated molecular mechanisms just started to translate into improved outcome. With regard to conventional chemotherapy multidrug resistance (MDR) is a persisting problem and the impact of ABCB1 (MDR1) expression is still controversially discussed. Methods: In this study we evaluated the ABCB1 expression using qRT-PCR and gene expression profiling (Affymetrix U133plus2.0 arrays) in 250 diagnostic AML samples derived from patients enrolled on a prospective treatment trial of the German-Austrian AML Study Group (AMLSG 07-04 trial; NCT00151242), in which patients were treated with an intensive anthracycline/cytarabine-based induction therapy. Findings were also evaluated in 154 TCGA AML cases receiving a 7+3 induction treatment (data available at http://cancergenome.nih.gov/) and put into perspective with previous reports. Furthermore, we investigated ABCB1 expression associated gene signatures and examined epigenetic regulation mechanisms by COBRA and methyl-CpG immunoprecipitation sequencing (MCIp-seq) in selected cases. Results: Our global analysis showed that patients who obtained a complete response (CR) following double induction therapy had lower ABCB1 mRNA levels compared to patients with refractory disease (RD) (p=0.07). Regarding cytogenetic AML subtypes, ABCB1 mRNA levels varied among the different cytogenetic groups with the complex karyotype group showing the highest ABCB1 and the inv(16) group the lowest ABCB1 expression levels. A comparison of CR versus RD cases within the cytogenetically determined prognostic groups showed that in the intermediate [CN-AML, t(11q23), and other intermediate risk cytogenetic aberrations (othersinter)] and poor risk groups (complex karyotype and othershigh), RD patients presented with significantly higher ABCB1 mRNA levels (p=0.02). Similarly, patients with favorable risk cytogenetics [t(8;21) and inv(16)], who achieved a CR, presented with lower ABCB1 levels compared to the ones, who were refractory. Patients with the lowest ABCB1 expression quartile (ABCB1low) showed significantly longer event-free survival (EFS) times than patients in the highest quartile cohort (ABCB1high) (median EFS 322 vs 105 days; p=0.02), while no differences were observed with regard to overall survival. In accordance, there was a significant enrichment of RD cases in the ABCB1high patient group (p=0.03). Next, in order to better understand the regulation of ABCB1 in AML, we specifically evaluated the DNA methylation level of a previously identified GC box important for ABCB1 expression regulation in CML and we performed global analyses of the entire ABCB1 5' region. While both analyses did not reveal significant differences, further investigation of an ABCB1 associated gene pattern showed a correlation with CD34 and KIT expression (p<0.001). This suggests that like in CML, ABCB1 might be regulated by WNT, and in line, normal CD34+ hematopoietic stem cells also showed high ABCB1 expression levels. Conclusions: In summary, our data provide further evidence for a potential impact of ABCB1 deregulation on the response to AML chemotherapy, especially in more stem cell like leukemia cohorts as well as cytogenetically high risk AML. While we are currently further investigating the involvement of the Wnt/β-catenin pathway in the regulation of ABCB1 transcription in AML, further integration of molecular findings are warranted to better decipher the underlying drug resistance mechanisms. Ultimately, these analyses will improve patient management by adding valuable predictive biomarkers. Disclosures No relevant conflicts of interest to declare.

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Consistent Hypofibrinogenemia Associated with Induction Anti-Tumor Chemotherapy for Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v116.21.1400.1400 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1400-1400

Author(s):

Zeina G Elamil ◽

Hande H. Tuncer ◽

Roy Tara ◽

Samer A. Al Homsi

Keyword(s):

Acute Myeloid Leukemia ◽

Platelet Count ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Daily Basis ◽

Normal Serum ◽

Induction Treatment ◽

Normal Range ◽

The Mean ◽

Acute Myeloid

Abstract Abstract 1400 Introduction: Hemostatic abnormalities are frequently encountered during initial presentation of acute myeloid leukemia (AML) as well as during induction treatment. Patients often present with decreased platelet counts and sometimes with abnormalities of the coagulation parameters with or without bleeding manifestations. In the absence of overt disseminated intravascular coagulopathy (DIC), transfusion practices during treatment are essentially based on the platelet count. Fibrinogen is an important element of the clotting mechanisms, constituting a template for both thrombin binding and the fibrinolytic system. We sought to determine the prevalence of altered serum fibrinogen levels during induction treatment in AML and its clinical significance. Methods: We prospectively measured serum fibrinogen on a daily basis in patients with newly diagnosed AML treated with induction anti-tumor chemotherapy at our institution from February 2007 to July 2010. Inclusion criteria included the diagnosis of AML and no overt DIC. Results: The study population included 17 patients (47% females) with mean age of 55.3 years (range 18 –80 years). At presentation, the mean platelet count was 62 × 109/L (range 3 – 252 × 109/L), the mean prothrombin time was 11.4 seconds (range 9.6–13.4 secs, normal range 10—13.7 secs), the mean international normalized ratio was 1.1 (range 0.9–1.3; normal range 0.9–1.1) and the mean activated partial thromboplastin time was 26.56 seconds (range 20.1–41 secs, normal range 22.3–34.0 secs). All patients had normal serum fibrinogen levels at presentation (mean 380.6 mg/dl; range 258–567 mg/dl; normal range 200–400 mg/dl). Thirteen patients were treated with idarubicin and cytarabine, 3 patients received a FLAG (fludarabine, cytarabine and G-CSF) regimen and one patient had amonafide and cytarabine. Serum fibrinogen levels were recorded on all patients on a daily basis (Figure 1). Nine (53%) developed hypofibrinogenemia on the fourth day of induction, 2 (12%) on day 5, 3 (17%) on day 6, 2 (12%) on day 7, and one (6%) on day 8 of the induction. Eight patients (47%) received prophylactic cryoprecipitate when the serum fibrinogen levels fell below 150 mg/dl. We did not observe a significant trend difference in serum fibrinogen levels between patients who received cryoprecipitate and those who did not. Serum fibrinogen levels were back to normal without transfusion support by day 6 for one patient (5.88 %), day 7 for 2 patients (11.76 %), day 8 for 3 patients (17.65 %), day 9 for one patient (5.88 %), day 10 for one patient (5.88 %), day 11 for 3 patients (17.65 %), day 12 for 6 patients (35.3 %). Conclusion: Patients with acute myeloid leukemia receiving induction chemotherapy may frequently develop isolated hypofibrinogenemia without evidence of disseminated intravascular coagulation. This finding is usually self-limited and disappears shortly after the completion of antitumor chemotherapy, usually by day 12. The mechanism of this under-recognized phenomenon is unclear. Its common occurrence raises questions about the appropriateness of transfusion practices in AML based solely on the platelet count and argues in favor of the need of more global tests such as thromboelastography. Disclosures: No relevant conflicts of interest to declare.

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Induction Treatment In Elderly Patients with Acute Myeloid Leukemia (AML): Randomized Comparison of Intermediate-Dose Cytarabine Plus Mitoxantrone (IMA) Versus Standard-Dose Cytarabine Plus Daunorubicin (DA) In 492 AML Patients >60 Years – Results From the SAL 60plus Trial

Blood ◽

10.1182/blood.v116.21.334.334 ◽

2010 ◽

Vol 116 (21) ◽

pp. 334-334 ◽

Cited By ~ 1

Author(s):

Christoph Röllig ◽

Michael Kramer ◽

Mathias Hanel ◽

Regina Herbst ◽

Norbert Schmitz ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Induction Treatment ◽

Term Survival ◽

Elderly Aml ◽

To Receive ◽

Acute Myeloid ◽

Intermediate Dose

Abstract Abstract 334 Background: The majority of patients diagnosed with Acute Myeloid Leukemia (AML) are older than 60 years. Although intensive induction chemotherapy is still the standard practice and a prerequisite for long-term survival, elderly patients have a higher risk of treatment related morbidity and lower remission rates than younger AML patients. An optimized induction treatment would combine high complete remission (CR) rates with tolerable toxicity. The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) has recently been reported to result in high CR rates (73.5%) with acceptable toxicity in 86 elderly AML patients (Niederwieser et al., Blood 2002, abstr. 1337). We present the results of a randomized-controlled trial (RCT) comparing efficacy and tolerability of IMA with the standard 7+3 induction regimen consisting of daunorubicin plus cytarabine (DA). Patients and Method: In the 60plus trial of the Study Alliance Leukemia (SAL, former DSIL), AML patients >60 years considered medically fit for chemotherapy were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 BID days 1,3,5,7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). All patients who achieved a CR received cytarabine based consolidation treatment (2+5/MAMAC). Primary endpoint was the CR rate with an expected difference of 15% based on the results of the study named above. Secondary endpoints were the incidence of serious adverse events (SAEs), time to relapse (TTR), disease-free survival (DFS), and overall survival (OS). Result: A total of 492 patients with a median age of 69 years (range, 61–84) were enrolled between 2003 and 2009 by 29 German centers. 248 were randomized to receive IMA and 244 to receive DA. Patient characteristics were similar in the two treatment arms. In the intention-to-treat analysis, the CR rate was 59.3% (95% CI, 53.1–65.2) in the IMA arm and 51.2% (95%CI, 45.0–57.4) in the DA arm (p= 0.085). Mortality during the first 2 months after the start of study treatment was 18.1% and 18.4% in the IMA and the DA arm, respectively. Forty-five SAEs and grade-4 non hematological toxicities in 43 patients (19%) were reported in the IMA arm, while there were 57 SAEs in 52 patients in the DA arm (23%; p=0.1866). After a median follow-up time of 25.7 months (2.1 years), the median TTR is 10.3 months for IMA and 11.1 months for DA (p=0.328), the median DFS is 10.2 versus 11.7 months (p=0.11) and the median OS is 9.7 versus 10.8 months for IMA versus DA (p=0.945). This results in a 1-year OS of 43.6% in the IMA arm and 46.9% in the DA arm. Conclusion: Our current results show an equal efficacy and toxicity of both induction regimens. The trend for a higher CR rate after IMA does not translate into a survival advantage. Thus, our study indicates that elderly AML patients do not benefit from a dose escalation of cytarabine in induction therapy. Disclosures: No relevant conflicts of interest to declare.

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FLAG-IDA As First Line Induction Treatment for Children De Novo AML

Blood ◽

10.1182/blood.v126.23.4900.4900 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4900-4900

Author(s):

Xiaoqin Feng ◽

Chunfu Li ◽

Lan He

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Induction Therapy ◽

Myeloid Leukemia ◽

De Novo ◽

Primary Study ◽

Induction Treatment ◽

First Line ◽

Acute Myeloid

Abstract Objective: The complete remission after induction therapy is very important for the prognosis of AML. Fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin (FLAG-IDA) regimen has been proven to be an effective chemotherapy for relapsed or refractory acute myeloid leukemia. The aim of this study was to evaluate complete remission rate and toxicity in children with de novo acute myeloid leukemia (none APL) who received the FLAG-IDA regimen as induction therapy. Method: Between March 2014 and July 20015, 14 children with de novo acute myeloid leukemia (none APL) were received FLAG-IDA regimen as first line induction treatment in our center. The regimen including: Fludarabine 30 mg/(m2.d), PI 0.5hr, qd, d2-6; Ara-C 2g/(m2.d), PI 3hr, d2-6; Ida (Idarubicin) mg/(m2.d), PI 1hr, qd, d4-6; G-CSF 5μg/(Kg.d), s.c./i.v. qd,d1-7. Of the 14 children, age 1-13 years old (median age 7 years old), including 2 (14.3%) children with favorable gene, 4 (28.6%) children with high risk gene. 3(21.4%) children received 1 cycle, 11 (78.6%) received 2 cycles of FLAG-IDA regimen. The CR rate and toxicity in total 25 cycles were evaluated. Result: After 25 cycles of FLAG-IDA regimen, only 1 child (7.1%) did not get CR, 13/14 (92.9%) got CR after 1 or 2 cycles of FLAG-IDA induction treatment. In 25 FLAG-IDA cycles, the neutropenic time was from 13-43 days (mean 24.8 days). In the induction period, 2(14.3%) children suffered sepsis, 3 children (21.4%) had proven invasive fungal infection. Of 14 children, 2 children(14.3%) combined with cutaneous anaphylaxis, 2 children combined with transient fever after venous transfusion of chemicals. None obvious cardiac toxicity (arrhythmia or heart failure) was proved. One child died of ARDS in the neutropenic period after 2nd FLAG-IDA cycle. Of 14 children, 12 children (85.7%) got continues CR with the follow up 1-19 months (median 8 months). Discussion: Our primary study showed quite high CR rate combined with quite toxicity but can be tolerated using the FLAG-IDA regimen as first line induction treatment. Comprehensive supportive care should be given during the induction therapy. The LFS and OS need to be feedback after long time follow up. Disclosures No relevant conflicts of interest to declare.

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Change in Treatments and Complications after Regionalizing High-Intensity Induction of Acute Myeloid Leukemia in a Community-Based Population, 2013-2017

Blood ◽

10.1182/blood-2019-123173 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3442-3442

Author(s):

Lisa Y Law ◽

Stephen Uong ◽

Gwendolyn Ho ◽

Hyma T. Vempaty ◽

David M. Baer ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Bone Marrow Transplantation ◽

Induction Therapy ◽

Marrow Transplantation ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Healthcare Delivery ◽

Community Based ◽

Acute Myeloid

Introduction: Patients with acute myeloid leukemia (AML) may receive more appropriate care when treated regionally instead of locally, but studies have not adequately accounted for baseline differences between regional and local cohorts. In 2015, Kaiser Permanente Northern California, an integrated healthcare delivery system, started to shift AML induction from local (N=21) to regional (N=3) centers. We assessed the association of regionalization with the frequency of use of induction therapy and bone marrow transplantation, and with 60-day mortality. Methods: Information for all adult health plan members with ≥1 year of enrollment before receiving a diagnosis of AML during 2013-17 was obtained from the electronic health record. Multivariable methods were used to compare risk of induction, bone marrow transplantation, and death before and after 2015 (i.e., 2013-14 and 2016-17) after adjustment for baseline characteristics. Results: Of 662 patients, 38% were ≥75 years, 30% had an Elixhauser comorbidity index ≥5, and 10% died within the week following diagnosis. Among non-APL patients, we observed increased use of induction therapy (65% vs 49%, p=0.0003) and bone marrow transplantation (23% vs 13%, p=0.007) after 2015, while the 60-day mortality rate did not change (before 2015, 94 of 278 [32.7%]; after 2015, 82 of 249 [32.9%]; p=0.83). Conclusion: In this community-based population that includes advanced elderly patients with substantial comorbidity, regionalization was associated with increased use of induction therapy and bone marrow transplantation but no increase in the risk of 60-day mortality. Older patients can benefit from AML induction therapy at specialized centers. Figure Disclosures No relevant conflicts of interest to declare.

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Biological and Clinical Features of Patients with Acute Myeloid Leukemia Bearing Trisomy 21

Blood ◽

10.1182/blood.v120.21.1488.1488 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1488-1488

Author(s):

Paolo Strati ◽

Hagop M. Kantarjian ◽

Jorge E. Cortes ◽

Farhad Ravandi ◽

Naveen Pemmaraju ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Clinical Features ◽

Trisomy 21 ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Induction Treatment ◽

Prognostic Impact ◽

Cell Transplant ◽

Increased Risk ◽

Acute Myeloid

Abstract Abstract 1488 Background: Individuals with congenital Trisomy 21 (+21) (Down syndrome) have an increased risk of developing acute myeloid leukemia (AML). As +21 in AML frequently occurs in association with other karyotypic abnormalities, its prognostic impact remains poorly defined. Thus +21 has been empirically categorized as an intermediate risk cytogenetic aberration. This study focuses on the biological and clinical features of +21 AML. Methods: We analyzed the records of all AML patients treated at MD Anderson Cancer Center (MDACC) between January 1995 and December 2011. Only patients presenting to MDACC at the time of diagnosis with no prior therapy were included. Four cytogenetic groups were defined: +21 alone, +21 plus favorable cytogenetics, +21 plus intermediate cytogenetics and +21 plus unfavorable cytogenetics (Grimwade D et al, Blood 2010). Progression free survival (PFS) was defined as time from diagnosis to relapse or last follow up. Survival curves were calculated using Kaplan-Meier estimates and were compared using the log-rank test. Results: A total of 90 patients harboring +21 aberrations at diagnosis were identified. Median age was 59 years (range, 18–88) and 58% were male. At diagnosis, median white cell count was 4.6 (0.6–190) × 109/L, hemoglobin 8.6 (3.3–13.4)g/dL, platelets 53 (4–395) × 109/L, peripheral blasts 17% (0–96), and bone marrow blasts 48% (0–97). FAB classification: M0–2 64%, M3 1%, M4–5 20%, M6 10%, M7 4%. Cytogenetic subgroups included: +21 alone: 12%, +21 with favorable: 8%, +21 with intermediate: 8%, and +21 with unfavorable: 72%. Molecular mutations: FLT3 4/49 (2 ITD, 2 D835) (8%), NRAS 4/53 (7%), NPM1 1/25 (4%), CEBPA 2/13 (15%) and CKIT 0/26 (0%). Induction regimens included: Idarubicin+AraC-based (IA) 36%, fludarabine-based (FLU) 24%, clofarabine-based (CLO) 11%, topotecan-based (CAT) 10%, hypomethylating-based (HMT) 11%, and miscellaneous (MISC) 8%. Overall Response Rate (ORR) was 54%. Clofarabine-based induction showed the highest frequency of complete remission (CR) (70%) and HMT the lowest frequency of CR (56%) (Table 1). Median time to CR (TTCR) from initiation of therapy for those patients achieving CR was 5 (3–19) weeks. Patients with +21 alone or treated with HMT had a significantly longer TTCR (p=0.038 and 0.006; respectively). Median PFS was 11 (2–130) months and median CR duration was 5 (1–100) months. PFS was significantly higher in patients with +21 alone (101 months) as compared to the intermediate and unfavorable group (11 and 2 months, respectively) (p=0.006). CR duration did not differ significantly among the 4 cytogenetic groups. Both PFS and CR duration did not differ significantly by induction regimen. Median Overall Survival (OS) for the entire group was 9 (0–130) months. Median OS for stem cell transplant (SCT) recipients (14 months) was significantly higher than those who did not undergo SCT (8 months) (p=0.003). Patients with +21 alone had better OS (32 months) than those in the intermediate and unfavorable groups (5 months and 2 months; respectively) (p <0.01). On multivariate COX regression, +21 alone group maintained an improved OS as compared to the intermediate and unfavorable groups (covariates were WBC, peripheral blasts, previous hematological malignancies, performance status, age and induction treatment)(p<0.001). Conclusions: Patients with AML harboring +21 aberrations have unique biological and clinical features. When present as a sole aberration it is associated with significantly improved PFS and OS. Thus +21 alone may be a favorable prognostic factor in AML. Disclosures: No relevant conflicts of interest to declare.

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Neutropenic fever prophylaxis during induction therapy for acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18531 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18531-e18531

Author(s):

Nassim H. Nabbout

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Standard Of Care ◽

Neutropenic Fever ◽

White Blood Count ◽

Induction Treatment ◽

Newly Diagnosed ◽

Oral Antibiotics ◽

Acute Myeloid

e18531 Neutropenic Fever Prophylaxis During Induction Therapy for Acute Myeloid Leukemia Nassim Nabbout, MD, Salam Kadhem, MD, Rawaa Ebrahem, MD, Rossa Khalaf, MD, Baharat Malhotra, MD, K. James Kallail, PhD Background: Neutropenic fever is an oncological emergency [1] that occurs at a high rate in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. Oral antibiotics have been considered standard of care for prophylaxis for these patients once they develop neutropenia [2]. To determine the efficacy of this approach, we conducted a retrospective review of newly diagnosed AML patients. Methods: All adult patients who underwent induction treatment for newly diagnosed AML at one Wichita, Kansas medical center between January 1, 2011 and December 31, 2013 were identified. The medical records were reviewed and pre-specified variables were collected. Results: Thirty-eight patients were included and their charts were reviewed. Nineteen (50%) were males. Thirty-six patients (95%) were white. The average white blood count on day 1 of treatment was 34000 cell/mm3 and the range was 1300 - 305,000 cell/mm3. The average ANC was 3700 cell/mm3 with the range of 10 - 28288 cell/mm3. All patients received prophylactic oral antibiotics once they became neutropenic. In all, but one patient, this regimen consisted of combination of levofloxacin, acyclovir, and fluconazole. Thirty-four patients (89%) developed neutropenic fever while they were on oral prophylactic antibiotics. Two patients (5%) developed septic shock. Four patients (11%) died during the first 21 days of induction, all due to infections, and three (8%) went to hospice. Causative organisms were identified in 11 patients (29%). All patients were switched to intravenous vancomycin and cefepime once they became febrile. Conclusions: Eighty-nine percent of patients developed neutropenic fever despite prophylaxis with oral antibiotics. These dismal results suggest that the current standard of care for neutropenic fever prophylaxis is ineffective and highlight the need for a different approach. Future studies should consider changing the regimens of antibiotics and/or the route of administration toward more aggressive prophylactic strategies.

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The Use of Cyclosporine in Association with Chemotherapy As Induction Treatment in Patients with Acute Myeloid Leukemia (AML) and High Rhodamine Efflux at Diagnosis Results in Higher Complete Hematological Remission Rates, but Does Not Prolong Overall Survival

Blood ◽

10.1182/blood.v126.23.4896.4896 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4896-4896 ◽

Cited By ~ 1

Author(s):

Luisa C A Koury ◽

Lorena Lobo Figueiredo-Pontes ◽

Belinda Pinto Simoes ◽

Luciana C O Oliveira ◽

Leandro F F Dalmazzo ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Conflicts Of Interest ◽

Induction Treatment ◽

Term Survival ◽

The Mean ◽

Hematological Remission ◽

Acute Myeloid

Abstract The overexpression of P-glycoprotein (Pgp) in leukemic blasts of Acute Myeloid Leukemia (AML) is associated with lower complete remission (CR) rates and shorter disease-free (DFS) and overall survival (OS). Cyclosporine A (CSA) is a competitive inhibitor of Pgp capable of reduce the P-gp mediated drug efflux. List et al. reported that CSA addition to treatment with cytarabine and daunorubicine reduced the resistance to induction treatment (IT) and prolonged DFS and OS. The effect was greater in AML patients with higher Pgp expression (Blood 2001; vol 98, n 12: 3212-20). Based on this study, we tested the effect of the association of CSA to IT in cases with high Pgp expression, which was established using the Rhodamine effux test as previously described (Pétriz, J. and García-López, J. Leukemia 1997; vol 11: 1124-30). The cut off value of the mean fluorescence intensity adopted to define high P-gp expression was ≥ 1.10. A total of 21 high P-gp AML patients were randomized in two groups: 1. Daunorubicin (DNR) 60mg/m² in continuous infusion -CI- 3x+Cytarabine 100 mg/m² CI 7x + CSA 16mg/m² CI 3x; (CSA group) and 2. DNR 60mg/m² CI 3x + Cytarabine 100 mg/m² CI 7x (Conventional IT group). Patients who did not achieve Complete Hematological Remission (CHR) in the first cycle of chemotherapy received a second course. The 2 groups did not differ regarding age (mean ± S.D.: 44.5 ± 11.9 vs. 48.5 ± 15.2 years in CSA and conventional IT group, respectively), leukocyte counts at diagnosis (44,200 ± 56,100 vs. 21,540 ± 20,200/µl), frequency of de Novo AML (81.8 vs. 80%) and of Core Binding Factor Leukemia cases (18.2 vs. 10%). The median follow up among survivors was of 6.2 years. The mean serum levels of CSA at 24 hours after infusion was of 1,157 ng/mL (range: 4 - 1,600ng/mL), which was similar to that reported by List et al. The CHR rate after the first cycle of induction was higher in the group using CSA (63.6% vs. 30%; p = 0.09) but the DFS (2.05 years vs. not reached; p= 0.27) and OS (4.08 vs. 21.12 months; p = 0.19) were higher in conventional IT group. These results may reflect the effect of the second course of induction in patients who failed to achieve CHR (CHR after second IT: 0% vs. 33.3%, p=0.34, in CSA and conventional IT group, respectively) and higher relapse rate in CSA group (42.8% vs. 33.3%, p=0.78). Furthermore, there was a lower frequency of induction deaths (18.2% vs. 9%; p = 0.59) and of hyperbilirubinemia (bilirubin > 1,5x the upper limit of normality) in the Conventional IT group (6 vs. 0 patients; p = 0.02). There were no cases of acute cardiac toxicity. The study was interrupted due to the cost of CSA and the lack of significant improvement in the outcomes. In conclusion, despite the higher rate of CR after one cycle of chemotherapy, there was not improvement in long term survival of AML patients with high Pgp expression treated with CSA in combination with anthracyclines and cytarabine. Disclosures No relevant conflicts of interest to declare.

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A Prospective Clinical Study of the Efficacy and Adverse Reactions of Azacitidine Combined with IA Regimen As the Induction Treatment of Newly Diagnosed AML

Blood ◽

10.1182/blood-2021-145026 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4408-4408

Author(s):

Lifen Kuang ◽

Juan Li

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Risk Group ◽

Induction Treatment ◽

Newly Diagnosed ◽

Significant Difference ◽

Acute Myeloid

Abstract Objective: This single-arm prospective research (ChiCTR2100044731) aimed to evaluate the efficacy and safety of azacitidine combined with IA regimen in the induction treatment of newly diagnosed acute myeloid leukemia (AML), with a view to further improving the efficacy of acute myeloid leukemia with poor prognosis. Methods: Newly diagnosed AML (non-M3) patients who received azacitidine combined with IA regimen induction chemotherapy in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University from November 2019 to February 2021 were enrolled, and the efficacy and side effect were analyzed. Results: A total of 33 patients were enrolled. The median age of the enrolled patients was 43.36 years (17-63), including 16 males (48.5%) and 17 females (51.5%). According to NCCN risk stratification, there were 3 patients (9.1%) in the favor group (9.1%) ,13 cases (39.4%) in the intermediate group and 17 cases (51.5%) in the poor group.The CR rate of one cycle of azacitidine combined with IA regimen was 66.7%, with a PR rate of 12.1% and a NR rate of 21.2%. After propensity score matching with the newly diagnosed AML patients who received IA regimen as induction chemotherapy in our center, a paired study was carried out. The results showed that there was no significant difference between the 2 groups in the treatment CR rate (66.7% for azacitidine combined with IA vs 54.5% for IA, P=0.592, Fig1). Subgroup analysis (table 1) showed combination of azacitidine with IA significantly improved the CR rate of patients with a ratio of blasts in the bone marrow greater than 67% (83.3% vs 30.8%, P=0.014) and patients in the intermediate NCCN risk group (100.0% vs 37.5%, P=0.001).The duration of agranulocytosis in the azacitidine combined with IA chemotherapy group was longer than that in the IA group (21 days vs 19 days, P=0.045). There was no significant difference in the number of platelet transfusions and the number of red blood cell transfusions between the two groups, and there was no significant difference in the incidence of infection between the two groups (table 2). Conclusions: The remission rate of induction chemotherapy for azacitidine combined with IA regimen and IA regimen in newly diagnosed non-M3 AML patients is comparable. Patients with a ratio of immature cells in bone marrow greater than 67% and patients in the intermediate NCCN risk group may benefit from azacitidine combined with the IA regimen. The combination of azacitidine with IA regimen aggravated granular bone marrow suppression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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