scholarly journals Impact of Race/Ethnicity on Pediatric Core Binding Factor AML Outcomes and Response to Gemtuzumab Ozogamicin

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Shannon E. Conneely ◽  
Casey L. McAtee ◽  
Rachel E. Rau
Keyword(s):  
Racial Differences ◽  
Black Children ◽  
Gemtuzumab Ozogamicin ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Hispanic Patients ◽  
Patient Variables ◽  
Race Ethnicity ◽  
The Impact ◽  
Target Database

Introduction: Racial disparities in pediatric acute myeloid leukemia (AML) outcomes have consistently demonstrated inferior event-free survival (EFS) and overall survival (OS) in minority populations with the worst outcomes in Black children. However, AML is a heterogenous disease classified by recurrent genetic aberrations, and these disparities have not been thoroughly investigated within specific cytogenetic groups. In addition, race-based response to individual chemotherapy agents in AML has not been explored. Here, we use data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to describe the effects of race on outcomes and response to gemtuzumab ozogamicin (GO) therapy in core binding factor (CBF) AML, a favorable risk AML subtype. Methods: CBF AML patient data was extracted from the online TARGET database. Race and ethnicity were self-reported. Estimates of 2-year OS and EFS were calculated using the Kaplan-Meier method and analyzed via log-rank statistic. Pearson's Chi-squared test and Fisher's exact test were used to analyze patient variables. Results: The OS in CBF AML differed significantly based on race/ethnicity at 87% (95% CI, 82-93%) for White non-Hispanic (WNH), 77% (95% CI, 67-89%) for Hispanic, and 71% (95% CI, 58-88%) for Black children (p=0.005). EFS was also significantly lower in Black (46%; 95% CI, 32-66%) compared to non-Black children (66%; 95% CI, 60-73%)(p=0.023). When assessed by CBF AML subtype, EFS and OS in t(8;21) AML varied significantly based on ethnicity at 50% (95% CI, 34-75%) and 67% (95% CI, 50-88%) in Black patients, 63% (95% CI, 49-82%) and 69% (95% CI, 55-87%) in Hispanic patients, and 82% (95% CI, 72-92%)(p=0.01) and 90% (95% CI, 93-98%)(p=0.006) in WNH patients. In inv(16) AML, Hispanic patients experienced the highest EFS (71%; 95% CI, 55-92%) followed by WNH (54%; 95% CI, 43-66%) and Black (36%; 95% CI, 17-79%) patients though this did not reach statistical significance (p=0.12). There was no impact of race/ethnicity on OS in inv(16) AML. The use of GO did not alter OS in any subset of CBF AML. EFS appeared to be slightly improved but was not statistically significant. However, Black children with any type of CBF AML had preferential improvement with GO with significantly higher EFS (69% v. 26%, p=0.03) and a trend toward improved OS (81% v. 63%, p=0.19) with GO therapy. These improvements were primarily driven by a significant increase in EFS in inv(16) AML when treated with GO (80% v. 50%, p=0.01) and a similar but non-significant improvement in OS in this group. In Hispanic children there was a trend toward inferior EFS with the use of GO (63% v. 73%, p=0.37) in CBF AML, particularly in t(8;21) patients with a 1-year EFS of 56% (95% CI, 37-87%) compared to 81% (95% CI, 64-100%)(p=0.23). WNH children were more likely to achieve Complete Remission (CR) after course 1 (OR 2.36, 95% CI 1.09-5.10, p=0.03), and Black children were more likely to have persistent Minimal Residual Disease (MRD) after course 2 (OR 9.64, 95% CI 2.48-37.43, p<0.001). No differences were detected in other patient variables. Conclusion: Children with CBF AML represent a favorable cytogenetic risk group with an EFS of 70% and OS of 85%. However, the impact of race/ethnicity on outcome is significant with Black children experiencing the lowest EFS and OS at 46% and 71%, respectively, with this trend persisting across cytogenetic subtypes. Black children were also more likely to remain MRD positive after Induction II and less likely than WNH patients to achieve CR. However, while the addition of GO to standard therapy did not improve outcomes in CBF AML overall, Black children selectively benefited from GO therapy. Black children trended toward improved EFS and OS with GO with the most pronounced effect on EFS in inv(16) which was improved from 50% to 80% at 1 year. These results demonstrate that Black children with CBF AML are disproportionately at risk for poor outcomes compared to other ethnicities, but these risks may be mitigated by the use of GO which increase EFS and OS primarily in this group. Conversely, Hispanic patients trended toward worse EFS with GO, particularly in t(8;21) AML, possibly due to treatment-related toxicity. As CD33 expression and certain ABCB1 SNPs are known to predict response to GO therapy, our ongoing work investigates racial differences in these variables as a potential explanation for the differing responses to GO. Disclosures Rau: Jazz Pharmaceuticals, Inc.: Consultancy, Other: Travel Fees.

Prevalence and Prognostic Significance of KIT Mutations in Pediatric Core Binding Factor AML Patients Treated with Gemtuzumab Ozogamicin: Results from the Randomized Phase III Children's Oncology Group Trial AAML0531

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 800-800
Author(s):  
Jessica Pollard ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Yi-Cheng Wang ◽  
Jason Joaquin ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Study Entry ◽  
Prognostic Impact ◽  
Core Binding Factor ◽  
Free Survival ◽  
Binding Factor ◽  
The Impact

Abstract Mutations of KIT (KIT +) occur in children and adults with core binding factor (CBF) acute myeloid leukemia (AML) and cluster within exons 8 and 17. We previously reported a 19% prevalence of KIT mutations in pediatric CBF AML and lack of prognostic significance in serial pediatric cooperative trials. We also determined that gemtuzumab ozogamicin (GO) improves outcomes for a subset of CBF AML patients with higher CD33 expression enrolled on AAML0531, a randomized trial of conventional chemotherapy with or without GO. Thus, in this study, we determined whether the clinical outcome of patients with KIT + CBF AML is affected by GO treatment. COG AAML0531 enrolled 1022 eligible pediatric de novo AML patients of which 247 had CBF AML [137 t(8;21) and 110 inv(16)/t(16;16)] based on central cytogenetic review. Of these 247 patients, 218 had evaluable samples for KIT mutational analysis. Analysis included PCR amplification of exons 8 and 17 and fragment length analysis and direct sequencing to identify all missense and size mutations. Mutations were detected in 55 patient samples (25%); 27 (49%) involved exon 8, 26 (47%) involved exon 17 and 2 (4%) involved both exons. Breakdown by exon and CBF translocation type demonstrated exon 8 mutations in 12/121 (10%) t(8;21) samples and 17/97 (18%) inv(16)/t(16;16)patient samples. Exon 17 mutations were found in 18/121 (15%) t(8;21) and 10/97 (10%) inv(16)/t(16;16) patient samples. Overall outcome analysis among the 218 CBF AML samples analyzed for KIT mutations revealed similar complete remission (CR) rates after induction I for KIT + vs. KIT- patients (83% vs. 82%, p=0.796). Five-year event-free survival (EFS) from study entry for KIT + vs. KIT- was 54% and 70%, respectively (p=0.029) with a corresponding overall survival (OS) of 76% vs. 83% (p=0.380). Notably, KIT + patients who achieved CR had a relapse risk (RR) of 45% vs. 23% for KIT- patients (p=0.010). Disease-free survival (DFS) for KIT + vs. KIT- was 51% and 72%, respectively (p=0.021). We also compared the clinical impact of exon 8 vs. exon 17 mutations. Outcomes of CBF AML patients with exon 8 mutations were similar to CBF AML patients without these mutations (OS 90% vs. 80%, p=0.277, EFS 55% vs. 68%, p=0.224, DFS 58% vs. 68%, p= 0.419, RR 42% vs. 26%, p= 0.112). In contrast, outcomes of patients with exon 17 mutations were inferior to those CBF AML patients without exon 17 mutations [OS 64% vs. 84%, p=0.035; DFS 43% vs. 70%, p=0.016) and higher RR was observed (48% vs. 26%, p=0.057). The impact of GO treatment on outcome was subsequently evaluated. KIT + CBF AML patients who did not receive GO had inferior OS and EFS from study entry compared to KIT-patients (OS 64% vs. 86%, p= 0.034, EFS: 46% vs. 69%, p=0.037). Higher RR (55% vs. 31%, p= 0.046) and inferior DFS (45% vs. 66%, p= 0.094) were also observed. In contrast, KIT + and KIT-patients receiving GO treatment had comparable outcomes (OS 88% vs. 80%, p=0.393; EFS 62% vs. 72%, p=0.438) as well as RR (33% vs. 15%, p=0.103) and DFS (57% vs. 77%, p=0.109). Analysis by mutation subtype revealed that outcomes of patients with exon 8 mutations were similar to exon 8 wild-type (WT) patients when treatment did not include GO (OS 81% vs. 80%, p=0.910; EFS 50% vs. 65%, p= 0.185). DFS and RR were also similar (DFS 57% vs. 62%, p= 0.752, RR 43% vs. 36%, p= 0.632). Treatment of exon 8 mutations with GO resulted in significant improvement in OS at 5 years from study entry compared to those without exon 8 mutations (100% vs. 80%, landmark p value <0.001) but other outcome parameters were not significantly improved (EFS 62% vs. 71%, p= 0.707; DFS 58% vs. 75%, p=0.382; RR 42% vs. 16%, p=0.056). For patients with exon 17 mutations, treatment without GO resulted in inferior outcomes when compared to CBF AML patients without exon 17 mutations (OS 56% vs. 85%, p= 0.019; EFS 44% vs. 66%, p=0.154; DFS 33% vs. 65%, p=0.049; RR 67% vs. 32%, p=0.031). Adding GO abrogated this negative impact. Specifically, OS, EFS, DFS and RR for patients with exon 17 mutations were comparable to that of CBF AML patients with WT exon 17 when treated with GO (OS 77% vs. 83%, p= 0.542; EFS 62% vs. 71%, p=0.516; DFS: 56% vs. 74%, p=0.195; RR 22% vs.19%, p=0.898). This analysis suggests that pediatric KIT + CBF AML has negative prognostic impact within the context of AAML0531. This effect was abrogated, particularly for patients with exon 17 mutations, with GO treatment. CD33-targeted agents may be beneficial, at least for a subset of these patients, in future clinical trials. Disclosures Aplenc: Sigma Tau: Honoraria.

scholarly journals Racial Differences in Disease Presentation and Management of Intracranial Meningioma

2018 ◽  
Vol 80 (06) ◽  
pp. 555-561
Author(s):  
C. Lane Anzalone ◽  
Amy E. Glasgow ◽  
Jamie J. Van Gompel ◽  
Matthew L. Carlson
Keyword(s):  
United States ◽  
Overall Survival ◽  
Racial Differences ◽  
Tumor Size ◽  
The United States ◽  
Intracranial Meningioma ◽  
Multivariable Model ◽  
Asian Populations ◽  
Hispanic Patients ◽  
The Impact

Objective/Hypothesis The aim of the study was to determine the impact of race on disease presentation and treatment of intracranial meningioma in the United States. Study Design This study comprised of the analysis of a national population-based tumor registry. Methods Analysis of the surveillance, epidemiology, and end results (SEER) database was performed, including all patients identified with a diagnosis of intracranial meningioma. Associations between race, disease presentation, treatment strategy, and overall survival were analyzed in a univariate and multivariable model. Results A total of 65,973 patients with intracranial meningiomas were identified. Of these, 45,251 (68.6%) claimed white, 7,796 (12%) black, 7,154 (11%) Hispanic, 4,902 (7%) Asian, and 870 (1%) patients reported “other-unspecified” or “other-unknown.” The median annual incidence of disease was lowest among black (3.43 per 100,000 persons) and highest among white (9.52 per 100,000 persons) populations (p < 0.001). Overall, Hispanic patients were diagnosed at the youngest age and white patients were diagnosed at the oldest age (mean of 59 vs. 66 years, respectively; p < 0.001). Compared with white populations, black, Hispanic, and Asian populations were more likely to present with larger tumors (p < 0.001). After controlling for tumor size, age, and treatment center in a multivariable model, Hispanic patients were more likely to undergo surgery than white, black, and Asian populations. Black populations had the poorest disease specific and overall survival rates at 5 years following surgery compared with other groups. Conclusion Racial differences among patients with intracranial meningioma exist within the United States. Understanding these differences are of vital importance toward identifying potential differences in the biological basis of disease or alternatively inequalities in healthcare delivery or access Further studies are required to determine which factors drive differences in tumor size, age, annual disease incidence, and overall survival between races.

Disparities at the Intersection of Race and Ethnicity: Examining Trends and Outcomes in Hispanic Women With Breast Cancer

2020 ◽  
pp. OP.20.00381
Author(s):  
Cosette D. Champion ◽  
Samantha M. Thomas ◽  
Jennifer K. Plichta ◽  
Edgardo Parrilla Castellar ◽  
Laura H. Rosenberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Racial Differences ◽  
White Women ◽  
Hispanic Women ◽  
Hazard Ratio ◽  
Tumor Subtype ◽  
Hispanic Patients ◽  
Race Ethnicity ◽  
Hispanic White

PURPOSE: We sought to examine tumor subtype, stage at diagnosis, time to surgery (TTS), and overall survival (OS) among Hispanic patients of different races and among Hispanic and non-Hispanic (NH) women of the same race. METHODS: Women 18 years of age or older who had been diagnosed with stage 0-IV breast cancer and who had undergone lumpectomy or mastectomy were identified in the National Cancer Database (2004-2014). Tumor subtype and stage at diagnosis were compared by race/ethnicity. Multivariable linear regression and Cox proportional hazards modeling were used to estimate associations between race/ethnicity and adjusted TTS and OS, respectively. RESULTS: A total of 44,374 Hispanic (American Indian [AI]: 79 [0.2%]; Black: 1,011 [2.3%]; White: 41,126 [92.7%]; Other: 2,158 [4.9%]) and 858,634 NH women (AI: 2,319 [0.3%]; Black: 97,206 [11.3%]; White: 727,270 [84.7%]; Other: 31,839 [3.7%]) were included. Hispanic Black women had lower rates of triple-negative disease (16.2%) than did NH Black women (23.5%) but higher rates than did Hispanic White women (13.9%; P < .001). Hispanic White women had higher rates of node-positive disease (23.2%) versus NH White women (14.4%) but slightly lower rates than Hispanic (24.6%) and NH Black women (24.5%; P < .001). Hispanic White women had longer TTS versus NH White women regardless of treatment sequence (adjusted means: adjuvant chemotherapy, 42.71 v 38.60 days; neoadjuvant chemotherapy, 208.55 v 201.14 days; both P < .001), but there were no significant racial differences in TTS among Hispanic patients. After adjustment, Hispanic White women (hazard ratio, 0.77 [95% CI, 0.74 to 0.81]) and Black women (hazard ratio, 0.75 [95% CI, 0.58 to 0.96]) had improved OS versus NH White women (reference) and Black women (hazard ratio, 1.15 [95% CI, 1.12 to 1.18]; all P < .05). CONCLUSION: Hispanic women had improved OS versus NH women, but racial differences in tumor subtype and nodal stage among Hispanic women highlight the importance of disaggregating racial/ethnic data in breast cancer research.

Effect of fludarabine, cytarabine, filgrastim, and gemtuzumab ozogamicin (FLAG-GO) on relapse-free survival in patients with newly diagnosed core-binding factor acute myelogenous leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6528-6528
Author(s):  
Gautam Borthakur ◽  
Jorge E. Cortes ◽  
Susan Mary O'Brien ◽  
Tapan M. Kadia ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Core Binding Factor ◽  
Platelet Recovery ◽  
Free Survival ◽  
Binding Factor ◽  
Acute Myelogenous

6528 Background: Prior modulation with fludarabine increases cytarabine-triphosphate (ara-CTP) accumulation and granulocyte-colony-stimulating factor (G-CSF) increases the fludarabine-triphosphate (F-ara-ATP) levels in leukemic blasts. Our front-line regimen of fludarabine, cytarabine and filgrastim (FLAG) based on this rationale showed improved event-free survival compared to anthracycline and cytarabine based regimens in patients (pts) with core-binding factor acute myelogenous leukemia (CBF-AML). Medical Research Council AML 15 trial reported survival benefit from addition of gemtuzumab ozogamicin (GO) to chemotherapy regimens in patients with favorable-risk cytogenetics AML. Methods: In a clinical trial combining GO (3 mg/m2 IV) with FLAG (FLAG-GO) in newly diagnosed CBF-AML, pts received GO on day 1 of induction and of post-remission cycles 2 or 3 and 5 or 6 in addition to FLAG. FLAG regimen was comprised of fludarabine 30 mg/m2 and cytarabine 2 gm/m2 IV daily (both for 5 days in induction and 3-4 days in post-remission cycles) with filgrastim started on day-1 and continued till neutrophil recovery. Pts who received one non-FLAG-GO induction could enroll irrespective of their remission status. Results: Fifty pts [30 with t(8;21) and 20 with Inv16] have been enrolled [5 of 50 (10%) were in remission at enrollment from prior induction]. Median age is 48 years (range, 19-76), median WBC count 12.3 x106/L (range, 1.3-97.2); 12 patients (24%) were >60 years of age and frequency of kit mutation is 8%. Complete remission with or without platelet recovery (CR/CRp) was achieved in 43/45 (96%) pts with 2 deaths in induction. With 6 planned consolidations, the median number of consolidation treatments received is 5 (range, 0-6). Two-thirds of pts needed dose reduction during post-remission cycles. Seven (14%) pts [t(8;21)= 5, Inv 16=2] relapsed and with a median follow-up of 34 months (range, 15-54 months) the relapse-free survival rate is 83%. Conclusions: FLAG-GO is a highly effective regimen and has resulted in high rate of relapse-free survival in pts with newly diagnosed CBF AML.

SNP-Array-Based Karyotyping Has Impact on Cytogenetic Diagnosis and Prognosis of Non-Core Binding Factor Primary and Secondary AML.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 597-597
Author(s):  
Ramon V. Tiu ◽  
Lukasz P. Gondek ◽  
Andrew J. Dunbar ◽  
Mikkael A. Sekeres ◽  
Matt E. Kalaycio ◽  
...  
Keyword(s):  
Copy Number Variants ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Point Mutations ◽  
Clinical Value ◽  
Core Binding Factor ◽  
Secondary Aml ◽  
Mutational Status ◽  
Binding Factor ◽  
The Impact

Abstract Non-core binding factor AML has heterogeneous clinical phenotypes, likely due to various modifying genetic lesions (i.e. point mutations such as Flt3, c-kit, or and nucleophosmin). Using metaphase cytogenetics (MC), chromosomal (chr.) abnormalities are found in only 50% of newly diagnosed patients with primary AML (pAML) and secondary AML (sAML) arising from MDS or MPD. Previously, we have demonstrated that SNP arrays (SNP-A) can detect previously cryptic lesions (including uniparental disomy, UPD) and enhance the clinical value of MC in patients with MDS. Here, we hypothesize that SNP-A will improve cytogenetic analysis in AML as well. Our study included 79 healthy control marrows and 103 AML cases; 36 pAML (FAB M0=3, M1=10, M2=10, M4=6, M5=6, M7=1; mean age 53y) and 67 sAML (from MDS, N=40 and MPD/MDS, N=27; mean age 63y). Normal MC was present in 69% and 45% of pAML and sAML, respectively. First, we investigated technical aspects of SNP-A karyotyping. Dilution studies showed that SNP-A can detect clones spanning 25–50% as well as LOH calls >99% of the time as shown X chr. analysis in males. Repetitive/serial testing demonstrated congruent results and somatic derivation of randomly selected lesions was confirmed by microsatellite and SNP-A of non-clonal cells. Copy number variants (CNV) encountered in controls or described in public databases were excluded. Using SNP-A, new cytogenetic abnormalities were found in 52% (28% UPD) and 59% (33% UPD) of pAML and sAML with normal MC, respectively. Moreover, 80% and 88% of pAML and sAML with previously abnormal MC harbored lesions detected by SNP-A. Examples of microdeletions/duplications include regions harboring known leukemia susceptibility genes, such as AML1. Segmental UPD involved regions often affected by deletion, including 5q, 7q, and 11q among others. Results of SNP-A can help characterize recurrent or minimally shared lesions, map their location, or identify causative genes. However, clinical utility of this technology is best demonstrated by the impact of the new defects on survival and other clinical parameters. In both pAML and sAML patients, we found that those with both normal MC and normal SNP-A had a better overall survival (OS) and event-free survival (EFS) as compared to those showing normal MC but abnormal SNP-A. (pAML: OS: p=.04, 21 vs. 5mo; EFS: p=.03, 19 vs. 6mo; sAML: OS: p=.04, 15 vs. 4mo; EFS: p=.04, 10 vs. 4mo). A subset analysis of those sAML patients derived from MDS showed similar results (OS: p=.02, 20 vs. 4mo; EFS: p=.03, 16 vs. 6mo). Most significantly, new lesions detected by SNP-A in AML patients with previously abnormal MC corresponded to a worse prognosis (OS: p=.0004, 10 vs. 3mo). For frequently encountered lesions, we performed survival analysis. For example, the presence of UPD7q negatively affected clinical outcomes (5 patients with UPD7 had equally poor survival to patients with del7/7q, N=10). Subset analyses (e.g., AML with normal MC) also indicated that chr. lesions detected by SNP-A impact stratification schemes independent of known risk factors such as Flt3 mutational status. In summary, SNP-A karyotyping allows for detection of previously cryptic cytogenetic lesions that together with routine MC may aid not only in diagnosis but prognosis in patients with both pAML and sAML.

Replacing Gemtuzumab Ozogamicin With Idarubicin In Frontline Fludarabine, Cytarabine and G-CSF Based Regimen Does Not Compromise Outcome In Core Binding Factor Acute Myelogenous Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3971-3971 ◽  
Author(s):  
Gautam Borthakur ◽  
Jorge E. Cortes ◽  
Farhad Ravandi ◽  
Graciela Nogueras Gonzalez ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Core Binding Factor ◽  
Free Survival ◽  
Log Reduction ◽  
Binding Factor ◽  
Acute Myelogenous

Abstract A regimen comprising of fludarabine, cytarabine, G-CSF and gemtuzumab ozogamicin (FLAG-GO) has been our frontline treatment regimen for patients with core binding factor acute myelogenous leukemia (CBF-AML) and among 50 patients with median follow up of over 3 years, this regimen resulted in overall survival (OS) and relapse free survival (RFS) of 78% and 85% respectively. This is clearly better than our historical data with idarubicin and cytarabine based regimens (Borthakur et al. JCO. Vol 28, No 15 suppl; 2010:6552). After withdrawal of GO from the market, it has been substituted by low dose idarubicin at 6 mg/m2 on days 3 and 4 in induction and in one post remission cycle during cycles 3-6 (FLAG-Ida). So far 38 patients have been treated with FLAG-Ida (median follow up 1 year) with all patients achieving complete remission. The current report is part of the planned analysis to ensure that patient outcomes have not been compromised by the change in regimen. Univariate and multivariate (MVA) Cox proportional hazards regression was used to identify association of the clinical variables with overall survival (OS), event free survival (EFS) and time to relapse (TTR). Event is defined as death from any cause or relapse. Treatment regimen (FLAG-GO or FLAG-Ida) were included as variables in the analysis. Apart from relevant clinical variables, reduction in fusion transcript ratio (in reference to ABL gene transcript compared to that at diagnosis) at time points 1 month (≥3 log reduction yes/no) and 3 month (≥3 log reduction yes/no) and presence of any mutation (RAS, KIT, FLT3 yes/no) were also added as variables. Stepwise backwards selection method was used to remove variables that did not remain significant in the multivariate model (p ≥ 0.15). T(8;21) is the cytogenetic abnormality in 52% of all 88 patients. Median age of all patients is 51 (range, 19-78 years) and 48% are female. Median time to 3 log reduction in transcript ratio was 1 month (range, 1-22 months). Complete remission rate with or without platelet recovery has been 98% with 2 induction deaths. Kaplan-Meier analysis showed OS (Fig.1), EFS and TTR were not significantly different FLAG-GO and FLAG-Ida regimens. By MVA, OS, EFS and TTR are not different among these regimens (p > 0.5). Three log or more reduction in transcript ration at 1 month was associated with better OS (p=.03) and EFS (p=.008) (not TTR) in MVA. Presence of KIT, RAS or FLT3 gene mutation did not impact outcomes studied. In conclusion, replacing GO with low dose idarubicin in a front-line FLAG regimen does not seem to compromise the excellent outcomes with such a regimen in CBF AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical and experimental efficacy of gemtuzumab ozogamicin in core binding factor acute myeloid leukemia

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Michele Gottardi ◽  
Federico Mosna ◽  
Sergio De Angeli ◽  
Cristina Papayannidis ◽  
Anna Candoni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Core Binding Factor ◽  
Free Survival ◽  
Binding Factor ◽  
Clonogenic Potential ◽  
Acute Myeloid

Leukemia-initiating cells of core binding factor (CBF) acute myeloid leukemia (AML) likely derive from early committed hematopoietic precursors expressing CD33. As such, targeting CD33 could ameliorate the chance of cure of CBF AML patients. We compared 12 CBF AML patients treated with Fludarabine, Cytarabine, Idarubicin and Gemtuzumab Ozogamicin (FLAI-GO regimen) with 25 CBF AML patients treated with the same schedule, but without GO. With the limit of small numbers, we observed a consistent trend toward better overall survival, disease free survival and event free survival in the FLAI-GO group. We also demonstrated the ability of GO to induce the disappearance <em>in vitro</em> of the AML1-ETO molecular transcript in a polymerase chain reaction-positive graft without decreasing the clonogenic potential of CD34+/CD38- cells. This represent the proof of principle for using GO in a purging strategy before autologous stem cell transplantation. Therefore, our data argue in favor of the reinstitution of GO in the therapy of CBF AML.

Sign in / Sign up

Export Citation Format

Share Document