A Comparative Retrospective Survey of Reinduction Chemotherapy Regimens for Acute Myeloid Leukemia (AML) in First Relapse: A Single-Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4273-4273 ◽  
Author(s):  
Andrew Brunner ◽  
Hossein Sadrzadeh ◽  
Lillian Werner ◽  
Karen K. Ballen ◽  
Yi-Bin A. Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Categorical Variables ◽  
High Dose ◽  
Single Institution ◽  
Significant Difference ◽  
First Relapse ◽  
Acute Myeloid

Abstract Abstract 4273 Introduction: Relapsed acute myeloid leukemia (AML) carries a poor prognosis. Although most newly diagnosed patients with AML achieve a complete remission after initial induction (CR1) using standard chemotherapy regimens, relapse follows in the majority of cases. The optimal reinduction chemotherapy regimen for patients following relapse remains unknown, and there is little comparative data to guide selection between various available reinduction regimens. The current study is a single-institution retrospective review over a 10 year period, which seeks to compare rates of response, disease-free survival (DFS) and overall survival (OS) between different reinduction regimens among patients with AML in first relapse. Methods: We performed a retrospective chart review of patients with AML who relapsed following CR1, and who were treated with reinduction chemotherapy at our institution between January 1, 2000, and December 31, 2010. Our patients were categorized into four groups based upon the type of reinduction chemotherapy they received: MEC (mitoxantrone, etoposide, cytarabine) or similar etoposide-containing regimens, 7+3 (infusional cytarabine and anthracycline) or 7+3-based regimens, HiDAC (high-dose cytarabine)-based regimens, and “other” combinations (less frequently used regimens including cytarabine and topotecan; decitabine; gemtuzumab; mitoxantrone and etoposide). Patients were identified using medical billing diagnosis codes, and included if they were above age 18 at diagnosis, obtained CR1 but experienced subsequent relapse, and were treated during first relapse with reinduction with intent to achieve remission. Exclusion criteria included patients with acute promyelocytic leukemia, primary refractory disease, and patients who were given chemotherapy for persistent disease on a mid-treatment bone marrow biopsy. Information about date of diagnosis, treatment regimens, tumor cytopathology and histology, comorbidities at diagnosis, and presenting laboratory data were collected. Statistical analysis was performed using the Kaplan-Meier method, and log rank tests where appropriate, to analyze DFS and OS. Fisher’s exact test was used to assess the associations between categorical variables. Results: We identified 66 patients who were treated with reinduction chemotherapy for AML in first relapse; of these, 28 (42%) achieved CR2. The type of reinduction chemotherapy received was not associated with any difference in the rates of CR2 (p=0.19). Patients who achieved CR2 had a median DFS of 5.1 months. For all patients, including those who failed to achieve CR2, the median OS following reinduction was 4.9 months. There was no significant difference in OS between re-induction regimens (p=0.09). However, there was a statistically significant difference in median DFS depending on regimen (p=0.006). Patients who received 7+3-based regimens, and to a lesser degree MEC, had longer median DFS than HiDAC-based regimens (8.9, 3.4, and 2.0 months, respectively). Patients who received 7+3-based re-induction regimens had a longer duration of preceding CR1 (p=0.006). Longer duration of CR1 (≥7.4 months, the median in our data) was associated with higher rate of CR2 (61% vs 22%, p=0.03) and OS (8.9 vs 2.9 months, p=0.0006) compared to duration of CR1 <7.4 months. Patients who were given “other” regimens (including demethylating therapies) were on average older (62 years old compared to 50, 52, and 54 years old in other groups); however, they had CR2 rates and OS similar to patients receiving 7+3, MEC, or HiDAC-based regimens. Conclusion: According to this retrospective analysis, patients treated with MEC or 7+3-based reinduction chemotherapy regimens had improved DFS compared to patients given HiDAC-based regimens. However, as expected, patients treated with 7+3-based reinduction chemotherapy were also more likely to have experienced a longer duration of CR1. Longer CR1 (≥7.4 months) was associated with improved DFS and OS following reinduction chemotherapy. It remains unclear whether the improved DFS seen in those AML patients who received 7+3-based regimens is due to the type of chemotherapy, or if this is related to the characteristics of their underlying disease, as manifested by the longer duration of CR1 seen in this treatment group. Our data does suggest that MEC may be preferable to HiDAC-based regimens for patients with early relapse following CR1. Disclosures: No relevant conflicts of interest to declare.

Salvage Chemotherapy Regimens for Acute Myeloid Leukemia: Is One Better?.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1022-1022
Author(s):  
Samantha L Price ◽  
Timothy J. George ◽  
Gene A Wetzstein ◽  
Jeffrey E Lancet ◽  
Alan F. List ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Categorical Variables ◽  
High Dose ◽  
Cell Transplant ◽  
Kaplan Meier ◽  
First Relapse ◽  
The Mean ◽  
Acute Myeloid

Abstract Abstract 1022 Poster Board I-44 Background: The vast majority of acute myeloid leukemia (AML) patients will relapse after initial therapy. Allogeneic hematopoietic cell transplant (AHCT) remains the only curative option in relapsed or refractory (RR)-AML. Currently, there is no standard or preferred regimen in the salvage setting. Regimens combining cladribine, high dose cytarabine and G-CSF (CLAG), or etoposide, cytarabine and mitoxantrone (MEC) in RR-AML yield complete remission (CR) rates of 50% and 66%, respectively (Wrzesieñ-Kuœ 2003, Amadori 1991). We hereby compare the efficacy of treatment with the CLAG and MEC regimens in RR-AML. Methods: A retrospective non-randomized comparison was performed for RR-AML patients who received CLAG or MEC regimens. The CLAG regimen consisted of: cladribine 5mg/m2/day IV on days 2-6, cytarabine 2gm/m2/day IV days 2-6 and filgrastim 300mcg daily on days 1-6. The MEC regimen included mitoxantrone 8mg/m2/day IV on days 1-5, etoposide 100mg/m2/day IV on days 1-5, cytarabine 1gm/m2/day IV on days 1-5. Data collected included baseline demographics and disease characteristics such as AML subtype, cytogenetics, duration of remission, prior therapies, response rates and overall survival (OS). The primary objective was to compare CR rates between the two regimens; the secondary endpoint was OS. International Working Group criteria were used to define CR. Primary refractory AML (PR-AML) in this study was defined as failure to achieve CR1 and less than 50% reduction in myeloblasts after first line of induction. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Results: Between January 2005 and June 2008, 162 patients were treated with CLAG or MEC for RR-AML. Patient baseline characteristics were similar between the two groups with respect to age, sex, FAB subtype, antecedent hematological disease history, cytogenetics, and prior therapy. The regimens were used as salvage for either PR- AML, or relapsed disease. Overall CR rates were CLAG, 38% (35/87) and MEC, 24% (15/63) (p= 0.048). The OS was 7.3 months for CLAG and 4.47 months for MEC, p=0.047. The mean length of stay was 31.2 vs. 32.5 days (range 2-107 days) respectively. For patients who received those regimens for PR-AML (n=55). No difference in the mean myeloblasts% at diagnosis or at time of reinduction was observed between the two regimens. CR rates were 45.5% (15/33) for CLAG and 22.2% (4/18) for MEC, p= 0.09. More patients treated with MEC (55.6%) had residual disease after treatment compared to CLAG (21.2%), (p=0.03). The median OS for the PR-AML patients who received CLAG was 10.97 months vs. 4.47 months for MEC (p=0.068). For Patients who were treated at time of first relapse (n=70), CR rates were CLAG, 36.8% (14/42) and MEC, 25.9% (7/28) (p=0.354). The OS in first relapse was similar between the two arms: CLAG 6.7 months and MEC 6.73 months (p=0.87). Among RR-AML patients ≤ 65 years, 36% of patients who received CLAG proceeded to AHCT compared to 25% with MEC. Conclusion: In this retrospective analysis, the CLAG regimen yielded significantly higher CR rates compared to MEC in RR-AML. There was a trend for improved OS particularly in the primary refractory setting, where CLAG regimen showed an additional OS benefit of 6.5 months. The higher CR rates and superior DFS and OS are clinically significant, supporting the use of CLAG as a preferred regimen for RR-AML patients. Disclosures: Off Label Use: CLAG and MEC regimens for AML.

scholarly journals High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1391-1395 ◽  
Author(s):  
RA Brown ◽  
SN Wolff ◽  
JW Fay ◽  
L Pineiro ◽  
RH Jr Collins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
High Dose ◽  
Allogeneic Bone ◽  
First Relapse ◽  
Total Body ◽  
Acute Myeloid

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.

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

Blood ◽  
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.

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

Blood ◽  
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.

Multidrug-Related Protein 1 (MRP1) Polymorphisms rs129081, rs212090, and rs212091 Predict Survival In Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2580-2580 ◽  
Author(s):  
Desiree Kunadt ◽  
Christian Dransfeld ◽  
Maria Schmiedgen ◽  
Michael Kramer ◽  
Christoph Röllig ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Significant Influence ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Npm1 Mutation ◽  
Significant Difference ◽  
Impact On Treatment ◽  
Acute Myeloid

Abstract Background ABCB1 (=MDR1, multidrug resistance protein 1) single nucleotide polymorphisms (SNPs) were shown to have a significant impact on therapy outcome in patients with acute myeloid leukemia (AML). Furthermore, an independent significant impact on treatment response and patient survival of SNPs in the genes for ABCC4 (MRP4), ABCC5 (MRP5) and ABCC11 (MRP8) related SNPs has also been demonstrated. In contrast, therapeutic strategies trying to modulate the anthracycline efflux of these transporters have failed in most clinical trials so far. Recently, higher dosages of daunorubicin used during induction chemotherapy have been associated with a better outcome in certain subgroups of AML patients. Hence, in times of individual diagnostic genetic analyses available as point-of-care diagnostics, the goal of this study was to further investigate whether SNPs in ABC-transporter genes, which are responsible for anthracycline efflux, have an independent impact on treatment outcome. Patients and Methods DNA samples were obtained from bone marrow aspirates of 160 Caucasian patients with newly diagnosed AML as part of the prospective AML2003 trial (NCT00180102). The cohort solely consisted of patients with a normal karyotype, based on conventional G-banding, minimizing false results in case of gain or loss of chromosomal material. All patients received double induction chemotherapy with daunorubicin and cytarabine. After DNA extraction, quantitative real time PCR was performed, using a total of 49 SNP assays investigating SNPs of seven different ABC genes. The identification of the corresponding SNPs was performed in an in silico analysis using the NIH dbSNP database and HapMap while statistical univariate and multivariate analyses were performed using SPSS. Results We detected three ABCC1 (MRP1) SNPs: rs129081 (CACCCC[C/G]ACTCCA), rs212090 (TTACTG[A/T]TCCCAC), and rs212091 (ACCTTA[A/G]AGAACA) with a significant influence on disease-free survival (DFS) or overall survival (OS), respectively. Patients carrying the homozygous rs129081 GG-SNP had a significant longer 5-year OS and 5-year DFS compared to the homozygous wildtype CC and heterozygous CG patients (OS: 68% [GG] vs. 40% [CC] vs. 64%, [CG], p=.035; DFS: 64% vs. 35% vs. 50%, p=.01). SNP rs212090 revealed a statistically significant difference in DFS when comparing homozygous alleles TT and AA (wildtype), 40% vs. 68%, p=.021. SNP rs212091 showed a significant difference concerning OS, with homozygous SNP GG leading to worse OS (0% vs. wildtype AA 64% vs. heterozygous AG 59%, p=.006). Again, there was a significant difference in DFS between both homozygous alleles AA (wildtype) and GG (55% vs. 0%, p=.018). Furthermore, there were no significant differences of standard clinical and laboratory baseline characteristics, FLT3-ITD mutation, or NPM1-mutation status, or chemotherapeutic toxicities. In order to exclude false positive findings of SNPs conferred as a result of leukemic transformation, we obtained saliva germline DNA from patients in complete remission who were treated by chemoconsolidation and performed a confirmatory analysis with the investigated SNPs, including rs129081, rs212090, and rs212091. Here, all SNPs were shown to be expressed in germline DNA in remission and bone marrow samples at diagnosis alike. The multivariate models for rs129081, rs212090 (TT), rs212091(AG), and rs212091(AA) revealed significances of p=.024, p=.029, p=.042, and p=.017 respectively for DFS but not for OS (except for rs212091[AA]). After adjustment for a false discovery rate of 5% still a trend towards the association of the SNPs and DFS could be seen. Therefore, more research is necessary to strengthen this evidence. Conclusion In this study we found a significant influence of rs129081, rs212090, and rs212091 SNPs (ABCC1, MRP1) on survival in AML in univariate analyses. Interestingly, these polymorphisms were not associated with other AML specific characteristics at diagnosis and were shown to be expressed in germline DNA and AML DNA alike. Hence, we suggest a prognostic effect of these SNPs which might be responsible for differential anthracycline susceptibility. Disclosures: No relevant conflicts of interest to declare.

Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4027-4033 ◽  
Author(s):  
Francis Giles ◽  
Norbert Vey ◽  
Daniel DeAngelo ◽  
Karen Seiter ◽  
Wendy Stock ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Continuous Infusion ◽  
Myeloid Leukemia ◽  
Controlled Study ◽  
High Dose ◽  
Double Blind Study ◽  
Double Blind ◽  
Median Response ◽  
First Relapse ◽  
Acute Myeloid

Abstract Laromustine is a sulfonylhdrazine alkylator with significant antileukemia activity. An international, randomized (2:1), double-blind, placebo-controlled study was conducted to compare complete remission (CR) rates and overall survival (OS) in patients with first relapse acute myeloid leukemia (AML) treated with laromustine and high-dose cytarabine (HDAC) versus HDAC/placebo. Patients received 1.5 g/m2 per day cytarabine continuous infusion for 3 days and laromustine 600 mg/m2 (n = 177) or placebo (n = 86) on day 2. Patients in CR received consolidation with laromustine/HDAC or HDAC/placebo as per initial randomization. After interim analysis at 50% enrollment, the Data Safety Monitoring Board (DSMB) expressed concern that any advantage in CR would be compromised by the observed on-study mortality, and enrollment was held. The CR rate was significantly higher for the laromustine/HDAC group (35% vs 19%, P = .005). However, the 30-day mortality rate and median progression-free survival were significantly worse in this group compared with HDAC/placebo (11% vs 2%; P = .016; 54 days vs 34; P = .002). OS and median response durations were similar in both groups. Laromustine/HDAC induced significantly more CR than HDAC/placebo, but OS was not improved due to mortality associated with myelosuppression and its sequelae. The DSMB subsequently approved a revised protocol with laromustine dose reduction and recombinant growth factor support. The study was registered as NCT00112554 at http://www.clinicaltrials.gov.

scholarly journals Differential Outcomes of Salvage with FLAG-IDA and Venetoclax-Based Regimens in Relapsed and Refractory Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4424-4424
Author(s):  
Ian M. Bouligny ◽  
Keri R. Maher
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Neutropenic Fever ◽  
Initial Diagnosis ◽  
Differential Outcomes ◽  
Significant Difference ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Sequencing and selection of salvage regimens for acute myeloid leukemia (AML) remains unclear. Venetoclax augmentation of a hypomethylating agent (HMA) backbone has joined the salvage armamentarium following impressive performance in the front-line setting. However, little is known about the outcomes with venetoclax in relapsed and refractory (R/R) AML. Survival and toxicity data remain scarce for venetoclax-based salvage, particularly when compared to intensive reinduction. This study characterizes outcomes between venetoclax-based salvage regimens and FLAG-IDA in the R/R setting. Patients & Methods: We retrospectively analyzed all patients with AML treated at Massey Cancer Center younger than 65 in the R/R setting with either FLAG-IDA (fludarabine, cytarabine, G-CSF, and idarubicin) or venetoclax in combination with decitabine, azacitidine, or low-dose cytarabine from June 2018 to December 2020. Baseline patient demographics and disease characteristics were obtained and recorded in RedCap. Statistical analyses using unpaired t-test with Welch's correction or the Mann-Whitney test, Fischer's exact test, and Kaplan-Meier survival analyses were computed and compared with log-rank tests using GraphPad Prism. The event for calculating the overall survival was the date of death with patients otherwise censored at the date of last contact. Results: Twenty-eight patients were identified meeting inclusion criteria: 19 underwent salvage with venetoclax-based regimens and 9 patients were treated with FLAG-IDA. Five patients (55.6%) in the FLAG-IDA cohort underwent salvage for refractory disease (primary induction failure), compared to only two (10.5%) in the venetoclax group, which was statistically significant (p = 0.019). The remaining patients in both cohorts were treated in the relapsed setting. There was no significant difference in sex (p = &gt;0.999), ECOG performance status at diagnosis (p = 0.083), or Charlson Comorbidity Index (CCI) scores (p = 0.128). The median age of patients treated with FLAG-IDA was 39 (range: 24 - 62), the four most common molecular mutations in the FLAG-IDA cohort occurred at a frequency of 22.2% each: FLT3-ITD, NPM1, WT1, and biallelic CEBPA. Two patients (22.2%) had favorable cytogenetics at diagnosis, one (11.1%) had intermediate cytogenetics, five (55.6%) had adverse cytogenetics, and one was unknown. All were initially treated with a 7+3 backbone. The most common non-hematological toxicities were neutropenic fever (55.6%) and acute kidney injury (22.2%). Five (55.6%) achieved CR and one (11.1%) achieved CRi for an ORR of 66.7%. There were no deaths within 60 days of salvage. Five (55.6%) patients went on to receive allogeneic SCT. Median survival was not reached at a median follow-up of 430 days (14.1 months). In the venetoclax-based cohort of 19 patients, the median age was 58 (range: 23 - 65), At the time of initial diagnosis, the most common molecular aberrations were TP53 (26.3%), NPM1 (15.7%), followed by FLT3-TKD, RUNX1, and TET2 (10.5% each). Two (10.5%) patients had favorable cytogenetics at initial diagnosis, two (10.5%) had intermediate, 14 (73.7%) had adverse cytogenetics, and one patient had unknown cytogenetics. Seventeen (89.5%) patients were initially treated with 7+3, one (5.3%) was treated with azacitidine, and one (5.3%) was treated with CPX-351. The most common non-hematological toxicities were infection (42.1%), neutropenic fever (31.6%), and GI toxicity (15.8%). Two (10.5%) patients achieved CR and four (21.1%) achieved CRi for an ORR of 31.6%. There were 3 deaths in 30 days and 1 death within 60 days. Four (21.1%) went on to receive allogeneic SCT after venetoclax-based salvage. The median survival was 268 days (8.81 months) and was statistically significant from the FLAG-IDA cohort (p = 0.0029). Conclusion: Our results suggest the efficacy of FLAG-IDA compared to venetoclax-based regimens with respect to ORR, survival, toxicity, and progression to transplant in the R/R setting for presumable intensive induction candidates, as evidenced retrospectively by prior receipt of such regimens. These differences may be impacted by changes to disease biology between the relapsed and refractory settings and TP53 status. Larger prospective studies with separate analyses between the relapsed and refractory settings are needed to confirm these findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

An Evaluation of Septicemia During Outpatient Consolidation Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4268-4268
Author(s):  
Lalit Saini ◽  
Mark D. Minden ◽  
Andre Schuh ◽  
Karen Yee ◽  
Aaron D Schimmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Infection Prophylaxis ◽  
Consolidation Chemotherapy ◽  
E Coli ◽  
Significant Difference ◽  
Ambulatory Patients ◽  
Gram Negative Organisms ◽  
Acute Myeloid

Abstract Abstract 4268 Introduction: Ambulatory chemotherapy for acute myeloid leukemia (AML) is believed to reduce exposure to nosocomial multi-drug resistant organisms and the incidence of septicemia. Materials and Methods: In this retrospective analysis we assessed the frequency of septicemia in patients receiving consolidation therapy: 256 patients received the first consolidation cycle (C1) and 217 the second consolidation cycle (C2). Patients received consolidation as inpatients or on an ambulatory basis. All ambulatory patients received infection prophylaxis with ciprofloxacin, amoxicillin and fluconazole. Results: 71 cycles of IP and 402 cycles of ambulatory consolidation chemotherapy were administered. Rates of bacteremia were higher in the IP cohort compared to the ambulatory patients (39.4% vs. 26.6%, p=0.028). IP in C1 but not C2 had significantly more septicemia then the ambulatory cohort within that cycle. Relative to C1, C2 was associated with significantly more bacteremia (p=0.03) and more Escherichia coli isolates (p=0.023) but there was no significant difference in the rates of total Gram-positive organisms (79.2% vs. 70.4%, p=0.32), total Gram-negative organisms (20.7% vs. 28.1%, p=0.32) or Streptococcus isolates (17% vs. 23.9%, p=0.34). All Streptococcus isolates in C2 were sensitive to penicillin despite amoxicillin prophylaxis whereas all E. coli strains in C2 were resistant to ciprofloxacin. Conclusions: Ambulatory consolidation chemotherapy for AML is associated with a reduced incidence of septicemia. The second consolidation cycle is associated with a higher incidence of bacteremia accounted for by increased rates of ciprofloxacin resistant E. coli and penicillin-sensitive Streptococcus. Disclosures: No relevant conflicts of interest to declare.

Acute Myeloid Leukemia: Longterm Outcome Predicted by Age and Genetic Groups

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1509-1509
Author(s):  
Thomas Buchner ◽  
Wolfgang E. Berdel ◽  
Utz Krug ◽  
Claudia Haferlach ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Multivariable Analysis ◽  
High Dose ◽  
Genetic Groups ◽  
Longterm Outcome ◽  
Acute Myeloid

Abstract Abstract 1509 Introduction: Both, patients' age and genetic groups are important predictors of outcome in AML while their influence remains poorly quantified and compared. Methods: In the AMLCG (Acute Myeloid Leukemia Cooperative Group) 1999 trial 1470 patients (pts) were 16–59y and 1747 pts were 60–85y of age. 95% of pts could be classified according to genetic risk groups as standardized on behalf of the ELN (Blood 2010;115:453-74). Their treatment was randomized between TAD-HAM versus HAM-HAM induction (TAD, standard dose thioguanine, cytarabine, daunorubicin 60mg/m2 × 3; HAM, high-dose cytarabine 3g/m2 × 6, mitoxantrone 10mg/m2 × 3), TAD consolidation and monthly maintenance vs TAD and autologous SCT, any chemotherapy + vs – G-CSF priming. All assignment was done upfront. Pts of <60y received routine double induction and full dose HAM while pts of 60+y preferentially received only 1 course induction and HAM at 1g instead of 3g cytarabine/m2 × 6. Results: With little difference according to randomizations, pts <60y and 60+y achieved a complete remission (CR) rate of 65% and 51% (p<.001), a 5y overall survival (OS) of 41% and 14% (p<.001), and a 5y ongoing remission duration (RD) of 47% and 21% (p<.001). We particularly focussed on pts around 60y of age and compared the 231 pts of 57–59y with the 315 pts of 60–62y. Corresponding to their similar age the two groups showed similar baseline characteristics. In contrast and due to the cutoff point for age adaption at 60y they differed considerably in treatment. Expressed by the cumulative dosage of cytarabine in induction and early consolidation, the difference between the two groups was by factor 3.9. This difference, however, did not translate into a different outcome being 60% vs 57% CR (p=0.59), 28% vs 25% 5y OS (p=0.40) and 32% vs 29% RD at 5y (p=0.46). Through focussing on patients around 60y a relevant influence of chemotherapy intensity and age adaption could thus be excluded. A multivariable analysis in the complete patients between 16 and 85y of age identified genetic groups and age (as a continuous variable) to be the only risk factors predicting CR, OS as well as RD whereas other risk factors such as secondary AML, WBC, and LDH were predictive only for subsets of endpoints. Among all treatment variables only HAM-HAM induction was associated with a slightly superior RD (p= 0.0715). Grouping by age resulted in 4 age categories (16–46y:n=683, 47–59y: n=787, 60–66y: n=815, and 67+y: n=932) with significantly different OS as well as RD. Subdividing by genetic groups (favorable: n=593, intermediate I: n=1169, intermediate II: n=526, adverse: n=780) distinguished 3 significantly different categories (favorable, intermediate, adverse), a pattern observed in all age groups. Conclusion: In a defined representative population of pts with AML the longterm outcome was mainly determined by age and genetic groups but not by treatment intensity or variables, nor by other prognostic factors. Both, age and genetic groups should thus contribute to a reliable prediction of outcome in AML. Disclosures: No relevant conflicts of interest to declare.

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