scholarly journals Prognostic Impact of Minimal Residual Disease Assessment in Elderly Patients with Secondary Acute Myeloid Leukemia. a Comparison between CPX-351 and Intensified Fludarabine-Based Regimens

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3442-3442
Author(s):  
Fabio Guolo ◽  
Paola Minetto ◽  
Marino Clavio ◽  
Maurizio Miglino ◽  
Riccardo Marcolin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Rt Pcr ◽  
Younger Patients ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Background: Minimal residual disease (MRD) assessment retains high prognostic value in Acute Myeloid Leukemia patients (AML) undergoing intensive induction therapy. Widely available MRD techniques include multicolour flow cytometry (MFC), RT-PCR for recurrent genetic lesion and, for patients lacking specific markers, RT-PCR for the pan- leukemic marker WT1. However, most of the data on the prognostic value of MRD come from trials including younger patients treated with conventional 3+7 regimen. AML arising from a previous myelodisplastic syndrome (s-AML) and therapy-related AML (t-AML) are usually under-represented in trial involving younger patients and are unlikely to respond to conventional induction. Few data are therefore available on the kinetics and the prognostic value of MRD in elderly s- AML and t-AML patients, particularly in the context of alternative induction regimens. Aims: We evaluated MRD in a cohort of elderly s-AML or t-AML patients receiving induction therapy either with a fludarabine-containing regimen or CPX-351, in order to compare the probability of achieving MRD negativity, to disclose the prognostic value of MRD in this setting and to define the best time-points for MRD assessments. Methods: A total of 136 elderly (>60 year, median age 67, range 60-75) patients were analyzed in this study. Patients were treated between January 2005 and January 2020 in our Center, either with CPX-351 (n=35) or fludarabine- high dose cytarabine-idarubicin (FLAI), with (n=72) or without (n =29) gemtuzumab-ozogamicin (GO). MRD was retrospectively analyzed in all patients achieving hematological complete remission (CR) with both MFC and WT1 expression levels.All patients were affected by s-AML or t-AML, defined according to the WHO 2016 criteria. Results: After induction, CR was achieved in 83 patients (61%). CR rate was 28/35 in patients treated with CPX-351 (80%), significantly higher when compared to patients receiving FLAI (55/101, 54.5%, p<0.05). The addition of GO to FLAI did not increase CR rate. Among CR patients, a total of 41 (49.4%) and 44 patients (53%) achieved MRD negativity, with MFC or WT1-based methods, respectively. MFC MRD negativity probability was higher among patients receiving CPX-351 as induction therapy (MFC MRD negativity rate of 16/28, 57% and 25/55, 45% in CR patients who received CPX-351 or FLAI, respectively, p<0.05). Adding GO to FLAI did not improve MRD negativity probability. Moreover, MRD showed significant prognostic value in terms of Overall Survival in all treatment group (2-year OS of 74 and 36% in patients with or without residual MFC MRD after induction, respectively, p<0.05). WT1-based MRD lead to similar results. Conclusion: In conclusion MRD assessment retains a strong prognostic value and may help to identify patients with suboptimal response to treatment. The higher rate of MRD negativity observed with CPX-351 may be related with a more efficient anti-leukemic activity of the drug in this particular setting. The evaluation of MRD with both MFC and WT1-based assessment lead to superimposable conclusions and allowed us to obtain MRD data from virtually all AML patients treated in the selected time period. Disclosures No relevant conflicts of interest to declare.

Core Binding Factor Acute Myeloid Leukemia In Pediatric Patients Enrolled In The AIEOP AML 2002/01 Trial: The Impact Of Minimal Residual Disease On Patient Outcome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3884-3884
Author(s):  
Martina Pigazzi ◽  
Valzerda Beqiri ◽  
Elena Manara ◽  
Roberto Rondelli ◽  
Riccardo Masetti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Rt Pcr ◽  
The Impact ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Introduction Acute Myeloid Leukemia (AML) accounts for 15% of pediatric leukemia. Improvements of prognosis achieved in the last twenty years are also due to a better stratification of patients into risk groups that allowed to deliver tailored treatment. The AIEOP LAM 2002/01 protocol classified patients with t(8;21)(q22,q22)AML1-ETO and inv(16)(p13;q22)CBFB-MYH11, who responded to induction therapy as belonging to the Standard-Risk (SR) group. These patients were considered at good prognosis; unfortunately, although they all reached morphological complete remission (CR) after the first induction course, they showed a high incidence of relapse (24%) (Pession A. et al., Blood 2013). At present, little is known about the kinetics of relapse or the development of resistance mechanisms; moreover, in many studies post-remission therapy in AML does not take into account the level of residual leukemia. Here, we evaluate the prognostic impact of molecular minimal residual disease (MRD) levels in terms of onset of relapse. Methods We studied bone marrow of 49 and 30 patients carrying either t(8;21) or inv(16) abnormalities, respectively, at time of diagnosis, and at the end of first and second course of induction therapy (ICE: Idarubicine, Citarabine and Etoposide). MRD was evaluated as number of fusion transcripts by quantitative RT-PCR using absolute quantification, and calculated as logarithmic (Log) disease reduction after the first and second ICE course as compared to diagnosis. Fusion transcripts were normalized to 10(5) ABL copies. The prognostic impact was assessed by the calculation of Overall Survival (OS) and cumulative incidence of relapse (CIR) according to the different MRD levels. Results After I ICE, t(8;21)-rearranged patients distributed equally in the four classes of MRD reduction. In particular, 10 patients reduced MRD levels of less than 1 Log, 11 patients reduced 1-2 Log, 17 patients reduced 2-3 Log and 11 patients reduced MRD levels of more than 3 Log as compared to diagnosis. After II ICE, the majority of patients increased the reduction of MRD levels (> 3 Log). We focused on the 10 patients who did not respond to the I ICE course and we found that 7 out of 10 reduced MRD levels of more than 1 Log after the II ICE, confirming a slow clearance of blasts for this subgroup of patients. We found that a reduction of MRD lower than 1 Log conferred a worst outcome to t(8;21)-rearranged patients (OS being 53.3% vs 85.2%, p=0.073 after I ICE; 33.3% vs 82.4 p= 0.062 after II ICE), and higher CIR after I and II ICE (52% vs 12.3%, p=0.0049, and 66.7 %, vs 17.2, p=0.024, at 6 years respectively). The group of inv(16)-rearranged achieved more than 1 Log reduction of MRD since I ICE course. After II ICE course, the majority of of patients reduced MRD of more than 3 Log, and 20% of them were completely negative. Inv(16) rearranged patients were all alive at last follow-up, and CIR never showed statistically significant differences for MRD levels in inv(16)-rearranged patients after the induction therapy. The impact of copy numbers (i.e. transcript levels) at diagnosis and after induction courses on relapse risk never showed significant results in both subgroups of CBF-rearranged patients. Conclusions Our data indicate that MRD evaluation using quantitative RT-PCR is an important diagnostic tool that permits the assessment of response to CT and the identification of patients at greater risk of relapse after induction therapy for AML1-ETO rearranged patients. We propose that at the end of induction therapy the cut-off of MRD< 1 Log be used to guide therapeutic decisions for this subgroup of SR patients. On the contrary, MRD levels of CBFB-MYH11 rearranged patients do not have prognostic value on CIR after induction therapy, this suggesting that novel molecular features should be investigated for this subgroup of AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

Haematologica ◽  
2017 ◽  
Vol 102 (9) ◽  
pp. e348-e351 ◽  
Author(s):  
Fabio Guolo ◽  
Paola Minetto ◽  
Marino Clavio ◽  
Maurizio Miglino ◽  
Federica Galaverna ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Minimal Residual ◽  
Acute Myeloid

scholarly journals Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia

Haematologica ◽  
2017 ◽  
Vol 102 (7) ◽  
pp. 1227-1237 ◽  
Author(s):  
Pierre Hirsch ◽  
Ruoping Tang ◽  
Nassera Abermil ◽  
Pascale Flandrin ◽  
Hannah Moatti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Minimal Residual ◽  
Acute Myeloid

Relation of Clinical Response and Minimal Residual Disease and Their Prognostic Impact on Outcome in Acute Myeloid Leukemia

2015 ◽  
Vol 33 (11) ◽  
pp. 1258-1264 ◽  
Author(s):  
Xueyan Chen ◽  
Hu Xie ◽  
Brent L. Wood ◽  
Roland B. Walter ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Minimal Residual ◽  
Acute Myeloid ◽  
Count Recovery

Purpose Both presence of minimal residual disease (MRD) and achievement of complete remission (CR) with incomplete platelet recovery (CRp) rather than CR after induction therapy predict relapse in acute myeloid leukemia (AML). These results suggest a correlation between response (peripheral count recovery) and MRD at the time of morphologic remission. Here we examine this hypothesis and whether MRD and response provide independent prognostic information after accounting for other relevant covariates. Patients and Methods We retrospectively analyzed data from 245 adults with AML who achieved CR, CRp, or CR with incomplete blood count recovery (CRi) after induction therapy. Bone marrow samples were collected on or closest to the first date of blood count recovery, and MRD was determined by 10-color multiparameter flow cytometry. Results The 71.0% of patients who achieved CR had MRD less frequently and had lower levels of MRD than the 19.6% of patients achieving CRp and 9.4% achieving CRi. Although pretreatment covariates such as cytogenetics, monosomal karyotype, relapsed or refractory rather than newly diagnosed AML, and FLT3 internal tandem duplication were associated with relapse, their prognostic effect was much lower once MRD and response were taken into account, the univariable statistical effect of which was not materially affected by inclusion of pretreatment covariates. Conclusion Our data indicate that post-therapy parameters including MRD status and response are important independent prognostic factors for outcome in patients with AML achieving remission. MRD status and type of response (CR v CRp or CRi) should play important, and perhaps dominant, roles in planning postinduction therapy.

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