Analysis Of Impact Of Distance From Residence To Treatment Center On The Outcome Of Patients With Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1712-1712 ◽  
Author(s):  
David W. Lam ◽  
Hossein Maymani ◽  
Michael G Machiorlatti ◽  
Samer A Srour ◽  
Minh Phan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Treatment Center ◽  
Cell Transplant ◽  
Tertiary Center ◽  
Remission Rates ◽  
The Impact ◽  
Acute Myeloid

Abstract Background The overall prognosis for most acute myeloid leukemia (AML) patients remains poor with only 50-55% of patients achieving durable remission. The majority of adult patients (pts) who do achieve remission, will ultimately need allogeneic stem cell transplant (allo-SCT) to achieve long term survival. Treatment of AML requires intensive therapy, transfusion support, antimicrobials, and repeated admissions to the hospital. Limited data is available comparing epidemiology and treatment according to the distance from patient residence to treatment center. Oklahoma University Health Sciences Center (OUHSC) is the major tertiary center for Oklahoma residents to receive treatment for AML. Few patients receive AML treatment from distant states or oversea areas. We describe a retrospective analysis of adult pts with AML treated at our institution evaluating impact on distance from center. Methods From January 2000 to June 2011,we identified a total of 269 patients with 217 meeting inclusion criteria for the study. We then performed an analysis of variance (ANOVA) on the relationship between distance to treatment center (in miles) and relapse rate or remission rates. Kaplan-Meier method was used to estimate survival rates. Age and cytogenetics were identified as the major confounders. A Cox Proportional Hazards model on overall survival (OS) was implemented using the independent variables age category ( ≤60 and > 60), cytogenetic risk status (groups were divided into favorable, intermediate and unfavorable risks), and distance to treatment center. Statistical analysis was performed using SAS 9.2 software (SAS Institute Inc.). Fisher’s exact test was used to compare patients in the different groups. Results Of the 217 pts (52.2% Males, 47.8% Females) included in the study, 81.5% were white, 9.0% African American, and 6.2% Native American. Median age at diagnosis was 51.0 years. Median distance to treatment center was 62 miles (range: 0-420). Distance of residence to treatment center was significantly related to complete remission rates, with patients living at longer distances having lower chances of achieving complete remission( p = 0.03). Distance from residence to treatment center however was not related to the risk of having relapsed disease (p = 0.22). A Cox proportional hazard model was performed including distance to travel, age and cytogenetic risks (unfavorable versus intermediate or favorable) and revealed that all three variables are associated with a trend towards shorter overall survival (p <0.1). Conclusions In this present study, we have identified that distance from residence to treatment center as a risk factor for achieving lower complete remission rate with no significant effect on the risk of relapse. There was a trend toward lower overall survival for those who live at longer distance from center. Further analysis of this dataset will identify the impact of other pretreatment variables on the distance to treatment center by performing a multivariate analysis. Larger studies are needed to further explore the impact of distance to treatment center on outcome in patients with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcomes of Adults With Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center

2021 ◽  
Vol 11 ◽  
Author(s):  
Matthew E. Tenold ◽  
Benjamin N. Moskoff ◽  
David J. Benjamin ◽  
Rasmus T. Hoeg ◽  
Aaron S. Rosenberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Comprehensive Cancer Center ◽  
Cell Transplant ◽  
Hypomethylating Agents ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Refractory Aml

Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8–24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

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

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

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

scholarly journals Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3294-3301 ◽  
Author(s):  
Mark Levis ◽  
Farhad Ravandi ◽  
Eunice S. Wang ◽  
Maria R. Baer ◽  
Alexander Perl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Randomized Trial ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Platelet Recovery ◽  
First Relapse ◽  
Acute Myeloid

AbstractIn a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.

The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2137-2145 ◽  
Author(s):  
Sabine Kayser ◽  
Konstanze Döhner ◽  
Jürgen Krauter ◽  
Claus-Henning Köhne ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Negative Impact ◽  
Primary Malignancy ◽  
De Novo Aml ◽  
The Impact ◽  
Acute Myeloid

Abstract To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Monosomy Karyotype in Acute Myeloid Leukemia Predicts Adverse Treatment Outcome with Low Complete Remission Rate and Worse Event-Free and Overall Survival, and Associates with High Functional Activity of Multidrug Resistance (MDR).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3112-3112 ◽  
Author(s):  
Hee Kyung Ahn ◽  
Dong Hwan (Dennis) Kim ◽  
Silvia Park ◽  
Jun Ho Jang ◽  
Kihyun Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Complete Remission ◽  
Functional Activity ◽  
Myeloid Leukemia ◽  
Marker Chromosome ◽  
Rhodamine 123 ◽  
Structural Abnormalities ◽  
Acute Myeloid

Abstract Abstract 3112 Poster Board III-49 Background It has been revealed that monosomy karyotype (MK), defined as 1) two or more distinct autosomal chromosome monosomies or 2) one single autosomal monosomy in the presence of structural abnormalities, identifies the highly unfavorable cytogenetic risk group of patients with acute myeloid leukemia (Breems, J Clin Oncol 2008), but lacking validation data. The current study aimed to validate the unfavorable impact of MK not only on overall survival (OS) but also on complete remission (CR) rate and event free survival (EFS) in AML patients. Methods A total of 370 consecutive AML (excluding APL) patients with available cytogenetic data who received treatment between 1995 and 2008 at the Samsung Medical Center, Seoul, Korea were included in this retrospective study, among whom 169 patients (45.7%) showed normal karyotype; 65 patients (17.6%), core binding factor (CBF) positive AML; and 136 patients (36.7%), non-CBF AML, respectively. Karyotypes were scored according to their structural abnormalities, monosomy, trisomy, deletion and marker chromosome. The CR rate, EFS and OS were compared according to the presence of each cytogenetic abnormality. In addition, multidrug resistance (MDR) functional assay (P-glycoprotein assay) was performed and MDR functional activity was calculated by verapamil-inhibited rhodamine-123 efflux activity minus uninhibited rhodamine-123 efflux activity, and positivity was determined as equal to or over 5% MDR activity. Results Among treated non-CBF AML group with any kind of cytogenetic abnormalities (n=136), 95 patients (69.9%) had structural cytogenetic abnormalities, 29 pts (21.3%), autosomal monosomy, 18 pts (13.2%), sex chromosome abnormalities, 59 pts (43.4%), autosomal trisomy, 41 pts (30.1%), deletion of part of a chromosome, 18 pts (13.2%), addition and 18 pts (13.2%), marker chromosome(s). MK was noted in 23 patients (16.9%), and complex karyotype (≥3 abnormalities) were found in 40 pts (29.%), -5 in 5 pts (3.7%), -7 in 12 pts (8.8%), del(5q) in 4 pts (2.9%), del(7q) in 8 pts (5.9%), inv(3) or t(3;3) in 4 pts (2.9%), t(6;9) in 5 pts (3.7%), and t(9;22) in 2 pts (1.5%). In univariate analyses, MK+ group was revealed to be associated with shorter OS and (median 10 vs 31months, p=0.044) EFS duration (median 1.3 vs 10.1 months, p=0.002), and a lower CR rate (70.8% vs 34.8%, p=0.002). In a multivariate analysis, MK was associated with lower CR rate (HR of non-CR 0.33, 95% C.I. 0.12-0.93, p=0.036). MK has been defined as a single monosomy with structural abnormalities or multiple monosomies in a previous study. However, there were no significant difference in survival and CR rate between a single monosomy with (n=9) or without(n=6) structural abnormalities (OS, 23 vs 8 months; p =0.349; EFS, 1 vs 9months; p=0.078; CR rate 33% vs 56%; p=0.608). The group with single autosomal monosomy showed a trend of better survival (n=15, median OS 23 months, EFS 1month) than multiple autosomal monosomy group (n=14, OS 6months, EFS 1month), but it was not significantly different (p = 0.322, p=0.221). The functional MDR activity was measured in 40 patients, and positive MDR activity was found to be significantly associated with the presence of MK (87.5% vs 33.3%, p=.013). In addition, the functional MDR activity was significantly higher in MK+ group (n=8, 45.9±17.8%, mean±S.E.) than in MK- group (n=32, 4.3 ±2.7%, p=0.005 by Mann-Whitney U-test). Conclusion The current study demonstrated that the AML patients harboring MK showed a poor outcome in terms of lower CR rate and worse EFS/OS in an independent cohort of Korean AML patients, and that MK karyotype was associated with high MDR functional activity of leukemic blasts. Disclosures No relevant conflicts of interest to declare.

Comparable Disease-Free and Overall Survival After “Well-Matched” Unrelated Donor and Matched Sibling Donor Transplantation in Acute Myeloid Leukemia with Adverse Risk Karyotype in First Complete Remission: A Report From the Acute Leukemia Working Committee of the Centre for International Blood and Marrow Transplant Research.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 526-526
Author(s):  
Vikas Gupta ◽  
Martin S. Tallman ◽  
Wensheng He ◽  
Brent Logan ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Allogeneic Hsct ◽  
Matched Sibling ◽  
Disease Free ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 526 In patients with acute myeloid leukemia (AML) in first complete remission (CR1), the indications for matched sibling donor (MSD) transplants and unrelated donor (URD) haemopoietic stem cell transplantation (HSCT) are different. We sought to determine the prognostic impact of donor type on the outcomes of AML with adverse risk karyotype in CR1, a high-risk AML population considered as a standard indication for MSD and URD HSCT. We evaluated the outcomes of 584 patients undergoing allogeneic HSCT for AML with adverse risk karyotype in CR1 between 1995 and 2006, reported to the CIBMTR. Adverse risk karyotype was defined according to SWOG/ECOG classification. Cytogenetics abnormalities were further classified as: complex karyotype (3 or more abnormalities), 32%; and Non-complex divided as abnormal chromosome 7, 25%; chromosome 5, 9%; MLL gene rearrangements, 18%; t (6;9), 5%; and others, 10%. 226 patients underwent MSD and 358 URD. URD were classified based on high resolution typing as:” well matched” [n=254 (71%)] with no known disparity at HLA A, B, C, DRB1; and, “partially matched” [n=104 (29%)] with one locus known or likely mismatched. Previous MDS was present in 19% and 14% had therapy-induced (t-AML). Conditioning regimens were myeloablative and reduced intensity in 74% and 26%, respectively. At 3 years treatment-related mortality (TRM) incidence was 28% (95% CI 24-31); relapse 36%(32-40); disease-free survival (DFS) 36%(32-41) and overall survival (OS) 39%(35-44). Multivariate analyses are summarized in the table. “Well matched” URD and MSD yielded similar DFS and OS, while outcomes were significantly inferior for “partially matched” URD. Cytogenetically defined subsets had similar outcomes. Evaluated as a time-dependent covariate, chronic GVHD had a significantly lower risk of relapse (RR 0.68, p=0.046), while acute GVHD had no effect (RR 0.99, p=0.96). “Well matched” URD and MSD lead to similar DFS and OS in AML CR1patients with adverse risk karyotype. The pool of patients who may benefit from graft-vs-leukemia effect generated with allogeneic HSCT may be considerably expanded with “well-matched” URD HSCT. If a suitable MSD is not availabel, “well-matched” URD should be strongly considered where a MSD HSCT would otherwise be undertaken. Disclosures: No relevant conflicts of interest to declare.

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