Increase in the Incidence of Secondary Acute Myeloid Leukemia (2-AML): A Single Institution Experience Over 20 Years.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1498-1498
Author(s):  
Elias Jabbour ◽  
Hagop M Kantarjian ◽  
Sherry Pierce ◽  
Guillermo Garcia-Manero ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Primary Cancer ◽  
Chromosome 11 ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Clonal Abnormalities

Abstract Secondary acute myeloid leukemia (2-AML) is a distinctive clinical syndrome occurring after primary malignancy treated or not with chemotherapy (CT), radiotherapy (RT), surgery, or a multimodality strategy. We analyzed the data on 2898 consecutive patients (pts) with AML (WHO criteria) referred to our institution between 1985 and 2005, including 1642 males and 1256 females. The median age was 58 years (range, 13–89 years) for pts with de novo AML (1-AML) (n=2198) and 66 years (range, 18–89 years) for those with 2-AML (n=700). 171 pts (18%) were treated for 2-AML between 1985 and 1994 versus 529 patients (27%) treated between 1995 and 2005 (p<0.001). The predominant primary malignancies included lymphoma (18%), breast (16%), and prostate (13%). Pts had been administered various cytotoxic chemotherapy agents (185 pts, 26%) and RT (102 pts, 15%); 182 (26%) had undergone both modalities, and 231 pts (33%) had undergone surgery alone. At diagnosis, 181 (26%) pts with 2-AML had diploid cytogenetics versus 845 (38%) pts with 1-AML (p<0.001). 252 (32%) pts with 2-AML had clonal abnormalities involving chromosomes 5 and 7 versus 383 (17%) pts with 1-AML (p<0.001), and 49 (7%) pts with 2-AML had 11q abnormalities versus 73 (3%) with 1-AML (p<0.001). Pts undergoing CT/RT had a worse cytogenetic risk profile compared to those undergoing surgery alone with more clonal abnormalities involving chromosomes 5 and 7 (36% versus 24%; p=0.002) and chromosome 11 (10% versus 2%; p<0.001), and less diploid karyotype (19% versus 39%; p<0.001). Median survival time after diagnosis of 2-AML was 6 months with 2- and 5-year survival rates of 18% and 11%, respectively. The median survival for pts treated with surgery alone for the primary cancer was 8 months versus 5 months for those receiving CT/RT (p=0.007); their 2- and 5-year survival rates were 22% and 14% and 16% and 9%, respectively. The median survival for pts treated for their primary cancer between 1985 and 1994 was 4 months versus 6 months for those treated after 1994 (p=0.089); their 2-year and 5-year survival rates were 16% and 9% and 19% and 12%, respectively. In conclusion, the incidence of 2-AML is increasing; patients receiving CT/RT had worse cytogenetic profiles and clinical outcomes than those receiving surgical treatment alone. There remains to be seen whether increased use of targeted therapies as prime modality of therapy in primary cancers will be associated with a decreased risk of 2-AML.

scholarly journals Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial

2021 ◽  
Author(s):  
Michael Heuser ◽  
B. Douglas Smith ◽  
Walter Fiedler ◽  
Mikkael A. Sekeres ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
De Novo ◽  
Secondary Acute Myeloid Leukemia ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

AbstractThis analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

scholarly journals Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: correlation with clinicobiologic findings [see comments]

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3688-3694 ◽  
Author(s):  
A Cuneo ◽  
A Ferrant ◽  
JL Michaux ◽  
M Boogaerts ◽  
H Demuynck ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Normal Karyotype ◽  
Clinical Findings ◽  
Trisomy 13 ◽  
Professional Exposure ◽  
Cytogenetic Profile ◽  
Acute Myeloid ◽  
Clonal Abnormalities

Cytogenetic data were studied in 26 patients with de novo acute myeloid leukemia (AML) with minimal myeloid differentiation, corresponding to the M0 subtype of the French-American-British classification, in correlation with cytoimmunologic and clinical findings. Clonal abnormalities were detected in 21 cases (80.7%), 12 of which had a complex karyotype. Partial or total monosomy 5q and/or 7q was found, either as the sole aberration or in all abnormal metaphases, in 11 patients; in 8 cases, additional chromosome changes were present, including rearrangements involving 12p12–13 and 2p12–15 seen in 3 cases each. Five patients had trisomy 13 as a possible primary chromosome change; in 5 cases, nonrecurrent chromsome abnormalities were observed. Comparison of these findings with chromosome data from 42 patients with AML-M1 shows that abnormal karyotypes, complex karyotypes, unbalanced chromosome changes (-5/5q- and/or -7/7q- and +13) were observed much more frequently in AML-M0 than in AML-M1. Patients with abnormalities of chromosome 5 and/or 7 frequently showed trilineage myelodysplasia and low white blood cell count. Despite their relatively young age, complete remission was achieved in 4 of 11 patients only. Patients with +13 were elderly males with frequent professional exposure to myelotoxic agents. Unlike patients with clonal abnormalities, most AML-M0 patients with normal karyotype showed 1% to 2% peroxidase-positive blast cells at light microscopy and frequently achieved CR. It is concluded that (1) AML-M0 shows a distinct cytogenetic profile, partially recalling that of therapy-related AML, (2) different cytogenetic groups of AML-M0 can be identified showing characteristic clinicobiologic features, and (3) chromosome rearrangements may partially account for the unfavorable outcome frequently observed in these patients.

scholarly journals MDR1 gene–related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3605-3611 ◽  
Author(s):  
Marry M. van den Heuvel-Eibrink ◽  
Erik A. C. Wiemer ◽  
Marjan J. de Boevere ◽  
Bronno van der Holt ◽  
Paula J. M. Vossebeld ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Genetic Polymorphism ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Clonal Selection ◽  
Survival Rates ◽  
Mdr1 Gene ◽  
Allelic Variants ◽  
P Glycoprotein ◽  
Acute Myeloid

The expression of P-glycoprotein (P-gp), encoded by theMDR1 gene, is an independent adverse prognostic factor for response and survival in de novo acute myeloid leukemia (AML). Little is known about MDR1 expression during the development of disease. The present study investigated whether MDR1 gene– related clonal selection occurs in the development from diagnosis to relapsed AML, using a genetic polymorphism of the MDR1 gene at position 2677. Expression and function of P-gp were studied using monoclonal antibodies MRK16 and UIC2 and the Rhodamine 123 retention assay with or without PSC 833. No difference was found in the levels of P-gp function and expression between diagnosis and relapse in purified paired blast samples from 30 patients with AML. Thirteen patients were homozygous for the genetic polymorphism ofMDR1 (n = 7 for guanine, n = 6 for thymidine), whereas 17 patients were heterozygous (GT). In the heterozygous patients, no selective loss of one allele was observed at relapse. Homozygosity for the MDR1 gene (GG or TT) was associated with shorter relapse-free intervals (P = .002) and poor survival rates (P = .02), compared with heterozygous patients. No difference was found in P-gp expression or function in patients with AML with either of the allelic variants of the MDR1 gene. It was concluded that P-gp function or expression is not upregulated at relapse/refractory disease and expression of one of the allelic variants is not associated with altered P-gp expression or function in AML, consistent with the fact that MDR1 gene–related clonal selection does not occur when AML evolves to recurrent disease.

scholarly journals Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4422-4429 ◽  
Author(s):  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Risk Groups ◽  
Complete Response ◽  
Intensive Chemotherapy ◽  
Acute Myeloid

Patients ≥ 70 years of age with acute myeloid leukemia (AML) have a poor prognosis. Recent studies suggested that intensive AML-type therapy is tolerated and may benefit most. We analyzed 446 patients ≥ 70 years of age with AML (≥ 20% blasts) treated with cytarabine-based intensive chemotherapy between 1990 and 2008 to identify risk groups for high induction (8-week) mortality. Excluding patients with favorable karyotypes, the overall complete response rate was 45%, 4-week mortality was 26%, and 8-week mortality was 36%. The median survival was 4.6 months, and the 1-year survival rate was 28%. Survival was similar among patients treated before 2000 and since 2000. A multivariate analysis of prognostic factors for 8-week mortality identified the following to be independently adverse: age ≥ 80 years, complex karyotypes, (≥ 3 abnormalities), poor performance (2-4 Eastern Cooperative Oncology Group), and elevated creatinine > 1.3 mg/dL. Patients with none (28%), 1 (40%), 2 (23%), or ≥ 3 factors (9%) had estimated 8-week mortality rates of 16%, 31%, 55%, and 71% respectively. The 8-week mortality model also predicted for differences in complete response and survival rates. In summary, the prognosis of most patients (72%) ≥ 70 years of age with AML is poor with intensive chemotherapy (8-week mortality ≥ 30%; median survival < 6 months).

Successful use of high-dose cytarabine in a patient with acute myeloid leukemia and severe hepatic dysfunction

2016 ◽  
Vol 22 (6) ◽  
pp. 811-815 ◽  
Author(s):  
Jacob A Barker ◽  
Bernard L Marini ◽  
Dale Bixby ◽  
Anthony J Perissinotti
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hepatic Dysfunction ◽  
Hematologic Malignancy ◽  
Survival Rates ◽  
Myeloproliferative Neoplasm ◽  
High Dose ◽  
Secondary Acute Myeloid Leukemia ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Acute myeloid leukemia is a hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and other tissues. Prognosis is poor with 5-year survival rates ranging from 5–65% depending on demographic and clinical features. Outcomes are worse for patients that have an antecedent myeloproliferative neoplasm that evolves to acute myeloid leukemia, with a survival rate of <10%. Treatment for acute myeloid leukemia has remained cytarabine and an anthracycline given in the standard 3 + 7 regimen. However, for patients with liver dysfunction this regimen, among many others, cannot be given safely. There is currently a lack of data regarding the use of cytarabine in patients with severe hepatic dysfunction. In this case report, we present a patient with secondary acute myeloid leukemia who successfully received a modified regimen of high-dose cytarabine while in severe hepatic dysfunction (bilirubin >15 mg/dL).

scholarly journals Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

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