Identification Of Low Risk Group In Infants With Acute Lymphoblastic Leukemia By Flow Cytometric Minimal Residual Disease Measurement At Day 15 Of Interfant-99 and Interfant-06 Protocols Treatment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1333-1333
Author(s):  
Alexander Popov ◽  
Barbara Buldini ◽  
Paola de Lorenzo ◽  
Emanuella Giarin ◽  
Annamaria Di Meglio ◽  
...  
Keyword(s):  
Residual Disease ◽  
Risk Group ◽  
Cox Model ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
Older Children ◽  
Flow Cytometric ◽  
Minimal Residual ◽  
Risk Of Relapse

Abstract Background Acute lymphoblastic leukemia (ALL) in infants is a relatively rare disease with peculiar biological features and worse outcome in comparison to ALL in older children. Infant ALL is characterized by a high frequency of MLL gene rearrangements, mainly CD10-negative B-cell precursor ALL (BCP-ALL) immunophenotype and high tumor burden at diagnosis. Even with new therapeutic approaches event-free survival (EFS) in this subgroup of patients does not exceed 50%. Although flow cytometric (FCM) minimal residual disease (MRD) detection at day 15 of remission induction is well established for patients' stratification in older children treated with the AIEOP-BFM-2009 protocol, the prognostic value of FCM MRD in infant ALL is not fully known yet. Aim of the present study was to evaluate the prognostic significance of FCM MRD measurement in infants with ALL treated with Interfant-99 and Interfant-06 protocols in AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) centers in Italy. Patients and methods Between May 1999 and December 2011, 120 consecutive infants aged 0 to 365 days with newly diagnosed ALL were treated in AIEOP centers with the Interfant99 and the on-going Interfant-06 protocols. Among these patients, 51 (42.5%) with available day 15 follow-up bone marrow samples were included in this study on FCM MRD. In 39 (76.5%) cases, different types of MLL gene rearrangements were identified by fluorescence in situ hybridization (FISH), while 12 (23.5%) patients had germline MLL. MRD detection was performed by 4-6-color FCM. Median follow-up time was 3.5 years (range: 1 month – 7.5 years). Outcome was estimated by evaluating the probability of EFS and the cumulative incidence of relapse (CIR). Analysis of prognostic relevance of FCM MRD in combination with other criteria used for stratifying patients enrolled in the Interfant-06 protocol was performed with the Cox model on the cause-specific hazard of relapse. Results and discussion We classified infants according to the AIEOP-BFM day 15 stratification into three risk groups: 14 patients (27.5%) were considered at standard risk (SR: MRD less than 0.1%), 9 patients (15.7%) at high risk (HR: MRD 10% or more), and the majority of infants (29, 56.9%) at intermediate risk (IR: MRD 0.1% to 10%). As the 14 SR patients had 3-year EFS and CIR significantly better than other patients, we considered two major groups of patients with different outcome: SR group (MRD<0.1%) with 3-year EFS 77.9% (standard error, SE, 11.3) and CIR 14.9% (SE 10.2), and non-SR group with 3-year EFS 32.0% (SE 8.5) and CIR 58.0% (SE 8.8, p=0.0104 and p=0.0085, respectively). Half of SR group (7 of 14 cases) had germline MLL. 4 out of 7 MLL-positive SR-patients were in continuous complete remission (CCR) In contrast, the majority of infants in the non-SR group carried various types of MLL rearrangements. Only 5 cases in the non-SR group were MLL germline and only two of them are still in CCR. We evaluated the prognostic impact of day 15 MRD in MLL-positive cases (n=39). In this cohort of patients, we also observed a difference, although not statistically significant, between SR and non-SR groups both in 3-year EFS (57.1%, SE 18.7 and 30.9%, SE 9.2, respectively; p=0.3630) and in 3-year CIR (28.6%, SE 18.9 and 60.9%, SE 9.5, respectively; p=0.1733). We evaluated the suitability of MLL negativity and of day 15 FCM MRD <0.1% as single criterion for the identification of low-risk patients. Each factor, when separately analyzed in a Cox model, was significantly correlated with a reduction in the risk of relapse, as shown in Table 1, left panel. Nevertheless, as day 15 FCM MRD levels are strictly related to MLL status, the Cox model which analyzes jointly the two factors, is unable to identify the one independently impacting on the risk of relapse (Table 1, right panel). Thus, although being a strong prognostic factor by itself, day 15 FCM MRD stratification did not confer an advantage in relapse prediction when considered in combination with MLL status, which is the only low-risk group criterion in the Interfant-06 stratification. Conclusion Day 15 FCM MRD proved to be a suitable variable predicting treatment failure and can be used as an alternative or in combination with Interfant-06 stratification criteria to identify SR patients. Disclosures: Popov: Alexion: Research Funding.

scholarly journals Comparative Value of the Assessment of Minimal Residual Disease in Peripheral Blood at Days 8 and 15 By Flow Cytometry in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5270-5270
Author(s):  
Marie Loosveld ◽  
Vanessa Nivaggioni ◽  
Isabelle Arnoux ◽  
Denis Bernot ◽  
Chantal Fossat ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
The Impact ◽  
Minimal Residual

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood, but treatments' progress now allowsto obtain prolonged remission or curein over 90% of the patients. Consequently, therapeutic de-escalation is now an objective for future treatment protocols, providing that biomarkers allow to reliablyidentifygood responders. Among such indicators, low levels of Minimal Residual Disease (MRD) obtained early after induction chemotherapy stand out as good candidates. The latter can be investigated usingmultiparameterflow cytometry (MFC) or real-time polymerase chain reaction (RT-PCR) for immunoglobulins or T-cell receptors (IG TCR) rearrangements. In this study we report the impact on survival of two early points of peripheral blood (PB) MRD assessment by MFC at days 8 and 15 on a cohort of 125 children with B-ALL enrolled in the French FRALLE trial and compared to molecular MRD in the bone marrow (BM) at day 35. Patients and methods. The study enrolled 67 boys and 58 girls and the duration of the study allowed for a median follow up of 52,1months. Median age at diagnosis was 57 months old (range 18 to 196), 101 children were between 1 to 10 years old and 24 were older than 10. Complete blood counts (CBC) at diagnosis showed a median of 6.7x109/L leucocytes (range 0.47 - 151x109/L) and 33% blasts (range 0 to 97%). One hundred and eight children had less than 50x109/L leucocytes while 17 had higher counts. EGIL classification at diagnosis allowed to classify patients as three B-I, 94 B-II, 27 B-III and 1 B-IV. Cytogenetic analyses were performed for 118 patients who were partitioned as follows: low risk n=47, intermediate risk n=55 and high risk n=16 (Harrisson CJ et al., BJH, 2010). Eighty-three patients were in the low risk group and 42 in the high-risk group as described by the FRALLE protocol. Seven patients of the 64 tested had an IKZF1 deletion. During the duration of the study, 20 patients relapsed and 8 died. Corticosensitivitywas defined by less than 1x109/L PB blasts on day 8 andchemosensitivity by less than 5% BM blasts on day 21 on BM smears. PB MRD was assessed in MFC with a single five or ten colors tube adapted to each patient's leukemia associatedimmunophenotypeon a backbone of CD45, CD19, CD10 and CD38. Statistical analyzes examined factors impacting disease-free survival (DFS) using Log rank test and Kaplan-Meier using theMedcalc® software (Ostend, Belgium). P values <0.05 were considered significant. Results None of diagnosis features had any significant impact on DFS: age (p=0,95), risk group (p=0,17), EGIL classification (p=0,55), cytogenetics (p= 0,87), leucocyte count (p=0,36) nor IKZF1 deletion (p=0,2). Of the 125 patients, 9 were corticoresistant, 79 corticosensitive and 37 not evaluable because of less than 1x109/L leucocyte at diagnosis.Corticosensitivity had no impact on DFS (p=0,11). Conversely,chemosensitivity had a significant positive impact on DFS (p= 0,009). Day 8 PB MRD did not oultlineany significantly different DFS, whether considering detectable vs undetectable MRD (p=0.65) or MRD levels (logwisefrom >10-1 to <10-4, p=0,22). Conversely, PB MFC at day 15 appeared highly discriminant. Considering notdetectablevs detectable MRD, 4 years DFS was 91,6+3% vs. 67,6+9% p=0,0013 (Figure 1). Further refining the thresholds of MRD logwisedid not modify the significance (p=0.004; Figure 2). Indeed, DFS at 48 months was 61+15 % (n=16) for MRD >10-3, 74+11% ( n=18) for MRD <10-3->10-4 and 92+3% ( n=91) for MRD<10-4. Comparison of PB MFC MRD on day 15 with day 35 BM molecular MRD showed concordance in 72% of the cases (83 negative/negative and 7 positive/positive, 48 months DFS 94.6+2.7% and 38+20% respectively). Eight patients were negative in PB but positive in BM (DFS 62.5+17%).Twenty seven where positive in PB but negative in BM (DFS 83.5+7.6%).These differences were statistically highly significant (p <0.0001). Conclusion This study demonstrates that even in the good prognosis context of childhood ALL, early MRD retains a highly significant prognostic value. It is of importance that this result was obtained not only on day 35 BM but interestingly, even earlier on day 15 PB. This less invasive procedure can easily be applied, especially for children. It should allow to detectgood responders, with MFC MRD levels below 10-4 for whom a de-escalation of chemotherapy could be considered. Conversely, the detection of blasts by MFC in day 15 PB is worrisome. Disclosures No relevant conflicts of interest to declare.

Patterns of Individual Tumor Response Testing (ITRT) and Bone Marrow Minimal Residual Disease (MRD) On Day 15 of Therapy in Childhood Precursor-B-Lineage Acute Lymphoblastic Leukemia (ALL): MRD and Ex Vivo Drug Resistance Have Similar Predictive Value of Relapse.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2448-2448
Author(s):  
Jan Styczynski ◽  
Anna Jaworska-Posadzy ◽  
Malgorzata Kubicka ◽  
Robert Debski ◽  
Beata Kurylo-Rafinska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
Multivariate Analysis ◽  
Residual Disease ◽  
Ex Vivo ◽  
Cox Model ◽  
Lymphoblastic Leukemia ◽  
Minimal Residual ◽  
Risk Of Relapse

Abstract Abstract 2448 Introduction: The speed of blast clearance during therapy is a major prognostic factor of outcome in childhood acute lymphoblastic leukemia (ALL). Blast count in the peripheral blood on day 8, or in the bone marrow on day 15 and day 33, have been widely used to deliver risk-directed therapy. Another approach to measure the speed of leukemia clearance is the detection of minimal residual disease during induction therapy, as well as at days 33 and 78 of therapy. In vitro measurements of drug resistance (called recently as ITRT, individual tumor resistance testing) in leukemic cells obtained at diagnosis have been of prognostic significance in the prediction of clinical outcome in selected groups of patients. Objective: The analysis of the prognostic impact of (A) residual disease (MRD) at day 15 of induction therapy; (B) in vitro drug resistance at diagnosis (ITRT), (C) correlation of MRD and ITRT, and (D) multivariate analysis of prognostic role of MRD, ITRT, initial factors and initial therapy response to the risk of relapse. Patients and Methods: A total number of 87 children (aged 1–18 years) diagnosed for pre-B-ALL, treated either with ALL-BMF-90 or ALL-IC-2002 protocol were included into the study. ITRT was tested at diagnosis by the MTT assay. Residual disease at day 15 was measured by flow cytometry and determined for cut-off value BML15<0.5%. The median follow-up was 8.9 yrs (range, 0–11.5). Following drugs were tested: prednisolone, dexamethasone, vincristine, L-asparaginase, daunorubicin, doxorubicin, etoposide and cytarabine. PVA score was determined as combined ITRT profile to prednisolone, vincristine and L-asparaginase. Results: (A) The overall pDFS was 0.721±0.052 and the mean survival 9.1 yrs (95%CI=8.2–9.9). Patients with BML15<0.5% had pDFS=0.816±0.055, while those with BML15>0.5% had pDFS=0.542±0.098 (p=0.009, log-rank). The risk of relapse in BML15-positive patients was 3.0-fold higher (1.3–7.1, p=0.013). (B) pDFS was significantly better for patients with sensitive ITRT profile to: PVA (1.00±0.00 vs 0.61±0.06, p=0.002), prednisolone (0.89±0.05 vs 0.54±0.08, p=00002), vincristine (0.84±0.06 vs 0.61±0.08, p=0.035), daunorubicin (0.094±0.04 vs 0.51±0.08, p=0.00002), and L-asparaginase (0.84±0.06 vs 0.59±0.08, p=0.009). In multivariate analysis in Cox model, the prognostic value was retained only for ITRT for prednisolone (p=0.013, HR=0.08, 95%CI=0.01–0.6) and daunorubicin (p=0.004, HR=0.05, 95%CI=0.01–0.4), while ITRT for PVA score was below of significance (p=0.068, HR=0.03, 95%CI=0.01–1.3). (C) Patients with MRD-positive ALL at day 15 (BML15>0.5%) had higher ITRT for following drugs: doxorubicin (p=0.005, RR=1.8, Mann-Whitney U test), L-asparaginase (p=0.029, RR=3.2), and etoposide (p=0.055, RR=4.1), while no differences were found for other drugs. In multivariate logistic regression, the significance impact to development of BML15>0.5% was found for doxorubicin (p=0.035, OR=0.33) and etoposide (p=0.048, OR=0.14). (D) In multivariate analysis in Cox model for relapse risk, three factors had predictive value: BML15>0.5% (p=0.010, OR=3.3, 95%CI=1.3–8.2), ITRT for prednisolone (p=0.012, OR=4.4, 95%CI=1.4–13) and ITRT for daunorubicin (p=0.018, OR=5.9, 95%CI=1.4–26), while age, prednisolone-poor-response at day 8, BM response at day 15, BM response at day 33, and BCR-ABL rearrangement had no significant value. Conclusions: Patients with residual disease at day 15 had 3-fold higher risk of relapse. Patients with resistant ITRT profile to prednisolone and daunorubicin had respectively 12- and 20-fold higher risk of relapse. Presence of residual blasts at day 15 correlates with ITRT to etoposide and doxorubicin. Finally, persistence of blast in marrow at day 15 (BML15>0.5%) and ex vivo drug resistance (ITRT) to prednisolone and to daunorubicin were the strongest prognostic factors predicting relapse in childhood ALL. Disclosures: No relevant conflicts of interest to declare.

Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1253-1258 ◽  
Author(s):  
Charlotte Nyvold ◽  
Hans O. Madsen ◽  
Lars P. Ryder ◽  
Jeanette Seyfarth ◽  
Arne Svejgaard ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Cox Model ◽  
Lymphoblastic Leukemia ◽  
Cell Disease ◽  
Excellent Outcome ◽  
Minimal Residual ◽  
Risk Of Relapse

The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day 15 (D15) and day 29 (D29) after the start of induction therapy (rs = 0.70, P &lt; .0001). The 15 patients with T-cell disease had higher D29 MRD than those with B-lineage ALL (P = .01). Age was positively related to D29 MRD (rs = 0.32, P = .001). The 16 patients who had a relapse had higher D15 and D29 MRD levels than the patients who stayed in remission (median levels D15, 1% versus 0.1%,P = .03; D29, 0.4% versus 0.01%,P = .0001). No patients with a MRD level less than 0.01% on D29 have so far had a relapse, whereas the 7-year probability of event-free survival for patients with higher MRD levels was 0.52 (P = .0007). The group of patients with a D29 MRD less than 0.01% included patients with T-cell disease, white blood cell count more than 50 × 109/L at diagnosis, or age 10 years or older, and could not be identified by up-front criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD (P = .004) and age (P = .009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a very low risk of relapse. Further trials are needed to reveal whether such patients with D29 MRD less than 0.01% can be cured with less intensive chemotherapy, which would reduce the risk of serious late effects as well as the costs of therapy.

scholarly journals Genotype-Specific Minimal Residual Disease Interpretation Improves Stratification in Pediatric Acute Lymphoblastic Leukemia

2018 ◽  
Vol 36 (1) ◽  
pp. 34-43 ◽  
Author(s):  
David O’Connor ◽  
Amir Enshaei ◽  
Jack Bartram ◽  
Jeremy Hancock ◽  
Christine J. Harrison ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Predictive Accuracy ◽  
Residual Disease ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Genetic Subtypes ◽  
Genetic Subtype ◽  
Minimal Residual ◽  
Risk Of Relapse

Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current risk algorithms dichotomize MRD data and do not assimilate genetics when assigning MRD risk, which reduces predictive accuracy. The aim of our study was to exploit the full power of MRD by examining it as a continuous variable and to integrate it with genetics. Patients and Methods We used a population-based cohort of 3,113 patients who were treated in UKALL2003, with a median follow-up of 7 years. MRD was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements, and patients were assigned to a genetic subtype on the basis of immunophenotype, cytogenetics, and fluorescence in situ hybridization. To examine response kinetics at the end of induction, we log-transformed the absolute MRD value and examined its distribution across subgroups. Results MRD was log normally distributed at the end of induction. MRD distributions of patients with distinct genetic subtypes were different ( P < .001). Patients with good-risk cytogenetics demonstrated the fastest disease clearance, whereas patients with high-risk genetics and T-cell acute lymphoblastic leukemia responded more slowly. The risk of relapse was correlated with MRD kinetics, and each log reduction in disease level reduced the risk by 20% (hazard ratio, 0.80; 95% CI, 0.77 to 0.83; P < .001). Although the risk of relapse was directly proportional to the MRD level within each genetic risk group, absolute relapse rate that was associated with a specific MRD value or category varied significantly by genetic subtype. Integration of genetic subtype–specific MRD values allowed more refined risk group stratification. Conclusion A single threshold for assigning patients to an MRD risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with MRD to accurately identify patients with the lowest and highest risk of relapse.

scholarly journals Minimal Residual Disease and IKZF1 As Predictors of Relapse, and Increased Treatment Related Mortality in Down Syndrome Acute Lymphoblastic Leukemia: A Unique and Large International Matched Case-Control Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 827-827
Author(s):  
Naomi Michels ◽  
Judith M. Boer ◽  
Marta Lopez-Yurda ◽  
Hester A. De Groot-Kruseman ◽  
Vincent van der Velden ◽  
...  
Keyword(s):  
Research Funding ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Induction Treatment ◽  
Free Survival ◽  
Minimal Residual ◽  
Risk Of Relapse ◽  
Treatment Related Mortality ◽  
Related Mortality

INTRODUCTION Down syndrome patients with acute lymphoblastic leukemia (DS ALL) are less likely to have a favorable (cyto)genetic subtype and are at higher risk of relapse and treatment-related mortality (TRM) than non-DS ALL (Buitenkamp et al., Blood 2014). At present, the independent predictive value of minimal residual disease (MRD) is unclear and may be biased by an unequal distribution of (cyto)genetic risk groups among DS ALL and non-DS ALL patients. This study was aimed to decipher the prognostic implications of MRD and IKZF1 deletions and the frequency of TRM in a matched cohort of DS ALL cases and non-DS ALL controls. METHODS Each DS ALL patient was matched to 3 non-DS ALL patients based on treatment protocol, induction treatment, cytogenetic subtype, IKZF1 status, age (cutoff at 10 years), and white blood cell count (cutoff at 50,000 cells/µl). For MRD analysis, matching was only on induction treatment and excluded the MRD-guided treatment arm; for survival analyses, matching included the MRD-guided treatment arm, thus resulting in two separately matched cohorts. Patients who died during induction were excluded from matching. Absolute MRD levels were measured with RQ-PCR, log-transformed and analyzed with a multilevel mixed-effects linear regression model. Matched Cox proportional hazard regression models were used to analyze event-free survival (EFS), overall-survival (OS), relapse-free survival (RFS) and mortality in remission as surrogate for TRM. RESULTS Patients treated between 2002 and 2018 on Dutch DCOG-ALL10/11 trials, Australian ANZCHOG-ALL8 and AIEOP-BFM-ALL2009 trials, and UKALL2003 trial were included, resulting in 160 DS ALL and 5313 non-DS ALL patients. Out of these 160 DS ALL patients, 13 died during induction versus 42/5313 non-DS ALL patients (8.1% versus 0.8%, p&lt;0.0001). Exclusion of induction deaths and patients with missing IKZF1 or MRD data, resulted in 110 DS ALL matched to study MRD differences (1 DS ALL could not be matched and was excluded), and 93 DS ALL matched to analyze survival (ALL11 was excluded due to short follow-up; 3 DS ALL could not be matched and were excluded). In the matched cohort, 22% (24/110) had favorable cytogenetics, 19% (21/110) had an IKZF1 deletion, 26% (29/110) were ≥10 years, and 17% (19/110) had a WBC ≥50,000 cells/µl. Only 3 cases (2 DS, 1 non-DS) did not achieve complete remission (excluding induction deaths). Median follow-up time of survivors was 7.1 years. The MRD levels did not differ between DS ALL and matched non-DS ALL patients at end of induction (p=0.96) nor when analyzed over time (p=0.43). In accordance, the 5-yr RFS did not differ between DS ALL and matched non-DS ALL patients (85 ± 4% versus 89 ± 2%, p=0.09). The 5-yr TRM of patients in remission was higher in DS ALL compared to non-DS ALL (11 ± 3% versus 3 ± 1%, p=0.001). In line, 5-yr EFS was lower in DS ALL compared to non-DS ALL patients (74 ± 5% versus 86 ± 2%, p=0.0007), as was 5-yr OS (77 ± 5% versus 93 ± 2%, p=0.0001). Multivariable analysis revealed that IKZF1 deletion can discriminate DS ALL patients at high risk of relapse (RFS: HR&gt;3, 95% CI=1-12, p=0.05). The effect of IKZF1 deletion was stronger in DS ALL patients than in the non-DS ALL patients in our cohort. CONCLUSION The MRD levels did not differ between DS ALL and non-DS ALL patients when matched for (cyto)genetics and other risk factors. In accordance, the overall relapse rate of DS ALL patients did not differ from that of matched non-DS ALL patients. Similar to non-DS ALL, IKZF1 deletion is an adverse risk factor for DS-ALL, indicating the need for treatment aimed at reducing the high relapse risk. DS ALL patients suffer more frequently from death in induction and from treatment while in remission, which jeopardizes treatment intensification. Therefore, the efficacy of targeted, less toxic therapies such as immunotherapies should be assessed in DS ALL. Disclosures van der Velden: Jansen: Research Funding; BD Biosciences: Research Funding; Amgen: Honoraria, Research Funding. Pieters:jazz farmaceuticals: Consultancy; medac: Consultancy. Zwaan:Celgene: Consultancy, Research Funding; Pfizer: Research Funding; BMS: Research Funding; Janssen: Consultancy; Servier: Consultancy; Roche: Consultancy; Incyte: Consultancy; Sanofi: Consultancy; Jazz Pharmaceuticals: Other: Travel support; Daiichi Sankyo: Consultancy.

Significance of Quantification of the PML-RARa Transcript in Children with Acute Promyelocytic Leukemia: A Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1474-1474
Author(s):  
Li Zhang ◽  
Zeng Cao ◽  
Yao Zou ◽  
Min Ruan ◽  
Qinghua Li ◽  
...  
Keyword(s):  
Complete Remission ◽  
Real Time ◽  
Minimal Residual Disease ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
Minimal Residual ◽  
Risk Of Relapse

Abstract Abstract 1474 Objective: Minimal residual disease (MRD) monitoring based on the detection of PML/RARa transcripts employing PCR technology has clearly demonstrated its benefit in the diagnosis and follow-up of acute promyelocytic leukemia (APL) patients. So far, real-time quantitative PCR (RQ-PCR) has been investigated to provide prognostic indexes for APL management in many adults studies. However, there are still no data on the use of such assays for child APL therapy. The aim of this study was conducted to clarify the relationship between the level of MRD and outcome in children with newly diagnosed PML/RARa-positive APL and identify the subgroups at low-risk of relapse. Methods: Since January 2004, we have analyzed 40 child patients treated with all-trans-retinoic acid (ATRA)±arsenic trioxide (ATO) in induction, with a median follow-up of 47 months. They were monitored by RQ-PCR. Hematologic and molecular relapses were recorded. We then looked for associations between relapse risk and RQ-PCR results in children. Results: The pretreatment characteristics of the 40 patients are listed in Table 1. Thirty-nine patients (97.5%) entered complete remission (CR). The 5-year probabilities of disease-free survival (DFS) and overall survival (OS) were 73.1% and 91.4%, respectively. By employing the standardized real-time quantitative polymerase chain reaction (RQ-PCR) for minimal residual disease (MRD) monitoring, no significant difference were observed in the PML/RARa normalized copy number (NCN) between patients in continuous complete remission and those who relapsed (neither at diagnosis nor after induction). After induction therapy, eight out of 25 cases with positive RQ-PCR (more than 1 NCN) relapsed in contrast to none out of 13 patients with negative RQ-PCR(100% and 55.2% DFS at 5 years in the negative and positive RQ-PCR groups, respectively; P=0.018, Fig.1). Also of note, in the positive RQ-PCR group, the patients treated with ATRA+ATO in induction had a lower relapse rate when compared with those treated with ATRA alone (P=0.03). Conclusions: PML/RARa - based MRD monitoring by RQ-PCR might allow us to identify subgroups of patients at low risk of relapse after induction in childen. Patients with a low risk of relapse could be monitored less frequently. Combination of ATO and ATRA might decrease the relapse rate compared with ATRA alone in induction therapy for childhood APL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals PROGNOSTIC SIGNIFICANCE AND TREATMENT IMPLICATIONS OF MINIMAL RESIDUAL DISEASE STUDIES IN PHILADELPHIA-NEGATIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014062 ◽  
Author(s):  
Orietta Spinelli ◽  
Manuela Tosi ◽  
Barbara Peruta ◽  
Marie Lorena Guinea Montalvo ◽  
Elena Maino ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Cure Rates ◽  
Sensitive Individual ◽  
Minimal Residual ◽  
Risk Of Relapse

Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. 

Sign in / Sign up

Export Citation Format

Share Document