scholarly journals GSTT1null and rs156697 Polymorphism in GSTO2 Influence the Risk and Therapeutic Outcome of B-Acute Lymphoblastic Leukemia Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Shahid M. Baba ◽  
Arshad A. Pandith ◽  
Zafar A. Shah ◽  
Sajad A. Geelani ◽  
Javid R. Bhat ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Gene Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Therapeutic Outcome ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Response To Chemotherapy ◽  
Increased Risk ◽  
And Gender

IntroductionGlutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case–control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population.MethodsA total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques.ResultsHigher frequency of GSTT1null, GSTO2-AG, and GSTO2-GG genotypes was observed in ALL cases compared to controls that associated significantly with ALL risk (GSTT1null: OR = 2.93, p = 0.0001; GSTO2-AG: OR = 2.58, p = 0.01; GSTO2-GG: OR = 3.13, p = 0.01). GSTM1, GSTP1, and GSTO1 SNPs showed no significant association (p > 0.05). Combined genotype analysis revealed significant association of GSTT1null/GSTM1null (OR = 4.11, p = 0.011) and GSTT1null/GSTP1-AG (OR = 4.93, p = 0.0003) with B-ALL susceptibility. Haplotype analysis of rs4925 and rs156697 revealed that carriers of CG haplotype had increased risk of B-ALL (p = 0.04). Kaplan–Meier plots revealed significantly inferior 3-year disease-free survival for GSTO2-GG carriers (p = 0.002). Multivariate analysis confirmed GSTO2-GG as an independent poor prognostic factor for DFS (HR = 4.5, p = 0.034). Among combined genotypes, only GSTT1null/GSTP1-AG associated significantly with poorer DFS rates (p = 0.032).ConclusionThis study demonstrated that GSTT1null individually or in combination with GSTM1null and GSTP1-AG genotypes associated with increased B-ALL risk. Also, rs156697 variant genotypes (AG and GG) associated with B-ALL, whereas the GG genotype of rs156697 influenced the treatment outcome.

Minimal residual disease by flow cytometry at the end of chemotherapy for remission induction in pediatric patients with acute lymphoblastic leukemia: Experience from a center in a low-income country.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9554-9554
Author(s):  
Eloy Perez ◽  
Primo Cruz-Borja ◽  
Silvia Chavez-Gallegos
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Increased Risk ◽  
Cure Rates ◽  
Minimal Residual

9554 Background: The presence of minimal residual disease (MDR) following therapy for acute lymphoblastic leukemia (ALL) has been shown to be an important prognostic marker in many studies. MRD is typically detected either by polymerase chain reaction amplification or by flow cytometry. Flow-based MRD assessment has the potential for rapidly identifying patients at increased risk of relapsed, allowing for prompt changes in therapy, including earlier intensification. There are not many information about the response by MRD in countries with limited resources. Methods: The patients included were 90 ALL patients treated at the Hospital Infantil de Morelia from June 1, 2009 to January 5, 2012. MRD positivity (+) was defined as >0.01% of the gated population. Results: MRD was obtained in 90 patients, 38 males and 36 females. The median age was 7 years (10 months to 15 years). The levels of MRD were: <0.01, 74 (82.2%), 0.01-1%, 9 (10%), ≥1%, 7 (7.7%). There was not a statistically significant association between the most important ALL prognostic factors (Gender, Age at diagnosis, White blood cell count at diagnosis, Central Nervous System disease, Prednisone response, DNA Index, Immunophenotype). Conclusions: The good response found is similar to that reported by international groups, a situation which suggests that the response to chemotherapy is appropriate. However, cure rates are still not equal making it necessary to review institutional treatment protocols and social characteristics of the population to achieve cure rates reported by international groups.

scholarly journals Improved results of treatment of adult acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1242-1248 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
CA Ries ◽  
MP Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Induction Phase ◽  
Free Survival ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Disease Free

Abstract We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Patient Stratification Based on Prednisolone-Vincristine-Asparaginase Resistance Profiles in Children With Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (17) ◽  
pp. 3262-3268 ◽  
Author(s):  
M.L. Den Boer ◽  
D.O. Harms ◽  
R. Pieters ◽  
K.M. Kazemier ◽  
U. Göbel ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Late Relapse ◽  
Early Event ◽  
Study Group ◽  
Increased Risk

Purpose: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. Patients and Methods: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. Results: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate ± SE was 69% ± 7.0%, 83% ± 4.4%, and 84% ± 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P ≤ .05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P = .03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P = .07). Conclusion: Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.

scholarly journals Open-wedge testicular biopsy in childhood acute lymphoblastic leukemia after two years of maintenance therapy: diagnostic accuracy and influence on outcome--a report from Children's Cancer Study Group

Blood ◽  
1990 ◽  
Vol 75 (5) ◽  
pp. 1051-1055
Author(s):  
J Nachman ◽  
NF Palmer ◽  
HN Sather ◽  
WA Bleyer ◽  
PF Coccia ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Testicular Biopsy ◽  
Current Therapy ◽  
Free Survival ◽  
Increased Risk ◽  
Subsequent Relapse ◽  
Negative Biopsies

Bilateral testicular biopsies were performed on 708 males with acute lymphoblastic leukemia completing 24 to 30 months of maintenance chemotherapy in continuous remission. The 73 patients (10.3%) with occult testicular leukemia (TL) had a significantly increased risk of subsequent relapse (P = .0001) and death (P less than .0001) when compared with patients with negative biopsies. Protocol-specified therapy for occult TL included reinduction therapy with concurrent bilateral testicular radiation, and 2 years of maintenance therapy. Four-year event-free survival for patients with negative biopsies was 78.2% +/- 4% versus 65% +/- 14% for patients with occult TL who received protocol-specified therapy (P = .05). This study suggests that (1) occult TL occurs in 10% of males completing 2 years of maintenance therapy; (2) occult TL significantly increases risk for subsequent relapse and death; (3) treatment results for occult TL and isolated overt off therapy TL (no previous biopsy) are similar; and (4) given current therapy, documentation of occult TL after 2 years of therapy does not improve disease-free survival.

scholarly journals Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group

2020 ◽  
Vol 38 (17) ◽  
pp. 1897-1905 ◽  
Author(s):  
Sumit Gupta ◽  
Cindy Wang ◽  
Elizabeth A. Raetz ◽  
Reuven Schore ◽  
Wanda L. Salzer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Early Response ◽  
Oncology Group ◽  
Increased Risk ◽  
Risk Patients ◽  
Landmark Analyses ◽  
The Impact

PURPOSE Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. Erwinia chrysanthemi ASNase ( Erwinia) substitution was approved in 2011 for allergic reactions. Erwinia has, however, been intermittently unavailable because of drug supply issues. The impact of Erwinia substitution or complete ASNase discontinuation is unknown. METHODS Patients aged 1-30.99 years in frontline Children’s Oncology Group trials for B-cell acute lymphoblastic leukemia between 2004 and 2011 (National Cancer Institute [NCI] standard risk [SR]: AALL0331; NCI high risk: AALL0232) were included. The number of prescribed pegaspargase (PEG-ASNase) doses varied by trial and strata. Maintenance therapy did not contain ASNase. Landmark analyses at maintenance compared disease-free survival (DFS) among those receiving all prescribed PEG-ASNase doses versus switching to Erwinia but receiving all doses versus not receiving all ASNase doses. RESULTS We included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG-ASNase discontinuation was 12.2% ± 4.6% in AALL0331 and 25.4% ± 0.8% in AALL0232. In multivariable analyses, NCI high-risk patients not receiving all prescribed ASNase doses had inferior DFS (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.9; P = .002) compared with those receiving all prescribed PEG-ASNase doses. Patients with Erwinia substitution who completed subsequent courses were not at increased risk (HR, 1.1; 95% CI, 0.7 to 1.6; P = .69). NCI SR patients who discontinued ASNase were not at elevated risk (HR, 1.2; 95% CI, 0.9 to 1.6; P = .23), except when restricted to those with slow early response, who were prescribed more ASNase because of therapy intensification (HR, 1.7; 95% CI, 1.1 to 2.7; P = .03). CONCLUSION Discontinuation of ASNase doses is associated with inferior DFS in higher-risk patients. Our results illustrate the severe consequences of Erwinia shortages.

scholarly journals Improved results of treatment of adult acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1242-1248
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
CA Ries ◽  
MP Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Induction Phase ◽  
Free Survival ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
Wbc Count ◽  
Disease Free

We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.

Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

1990 ◽  
Vol 8 (4) ◽  
pp. 672-677 ◽  
Author(s):  
C Uderzo ◽  
M Grazia Zurlo ◽  
L Adamoli ◽  
L Zanesco ◽  
M Aricò ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Multicenter Study ◽  
Lymphoblastic Leukemia ◽  
Systemic Disease ◽  
Disease Free Survival ◽  
Maintenance Phase ◽  
Treatment Withdrawal ◽  
Induction Phase ◽  
Kaplan Meier ◽  
Total Treatment

Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

scholarly journals Open-wedge testicular biopsy in childhood acute lymphoblastic leukemia after two years of maintenance therapy: diagnostic accuracy and influence on outcome--a report from Children's Cancer Study Group

Blood ◽  
1990 ◽  
Vol 75 (5) ◽  
pp. 1051-1055 ◽  
Author(s):  
J Nachman ◽  
NF Palmer ◽  
HN Sather ◽  
WA Bleyer ◽  
PF Coccia ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Testicular Biopsy ◽  
Current Therapy ◽  
Free Survival ◽  
Increased Risk ◽  
Subsequent Relapse ◽  
Negative Biopsies

Abstract Bilateral testicular biopsies were performed on 708 males with acute lymphoblastic leukemia completing 24 to 30 months of maintenance chemotherapy in continuous remission. The 73 patients (10.3%) with occult testicular leukemia (TL) had a significantly increased risk of subsequent relapse (P = .0001) and death (P less than .0001) when compared with patients with negative biopsies. Protocol-specified therapy for occult TL included reinduction therapy with concurrent bilateral testicular radiation, and 2 years of maintenance therapy. Four-year event-free survival for patients with negative biopsies was 78.2% +/- 4% versus 65% +/- 14% for patients with occult TL who received protocol-specified therapy (P = .05). This study suggests that (1) occult TL occurs in 10% of males completing 2 years of maintenance therapy; (2) occult TL significantly increases risk for subsequent relapse and death; (3) treatment results for occult TL and isolated overt off therapy TL (no previous biopsy) are similar; and (4) given current therapy, documentation of occult TL after 2 years of therapy does not improve disease-free survival.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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