Addition of rubidomycine to induction treatment with vincristine, prednison and L-asparaginase in standard risk childhood acute lymphocytic leukemia

1986 ◽  
Vol 10 (1) ◽  
pp. 112 ◽  
Author(s):  
A.v.d. Does-v.d. Berg ◽  
E.R.v. Wering ◽  
J.d. Koning ◽  
J.A. Rammeloo ◽  
G. Solbu ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Standard Risk

scholarly journals Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment

2020 ◽  
Vol 10 ◽  
Author(s):  
Geise Ellen Broto ◽  
Stephany Corrêa ◽  
Fausto Celso Trigo ◽  
Everton Cruz dos Santos ◽  
Fernanda Tomiotto-Pelissier ◽  
...  
Keyword(s):  
Transcription Factor ◽  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Induction Phase ◽  
Label Free ◽  
Childhood Diseases ◽  
Coagulation Proteins ◽  
Ifn Γ

Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. Despite recent advances concerning disease treatment, cytotoxic chemotherapy remains the first line of treatment in several countries, and the modifications induced by such drugs in the organism are still poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-ALL treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. To reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Proteomic data was available via ProteomeXchange with identifier PXD021584. The resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways, and transcription factors altered by chemotherapy, as well as to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin, and plasminogen. D28 was characterized predominantly by immune response-related processes and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. We chose to validate the proteins transthyretin and interferon-gamma (IFN-γ) by commercial kits and expressed the results as PB/BM ratios. Transthyretin ratio was augmented after induction chemotherapy, while IFN-γ was reduced at the end of the treatment. Considering that most of these proteins were not yet described in B-ALL literature, these findings added to understanding disease biology at diagnosis and highlighted a possible role for transthyretin and IFN-γ as mechanisms related to disease resolution.

Consolidation therapy with antimetabolite-based therapy in standard-risk acute lymphocytic leukemia of childhood: a Pediatric Oncology Group Study.

1998 ◽  
Vol 16 (8) ◽  
pp. 2840-2847 ◽  
Author(s):  
M B Harris ◽  
J J Shuster ◽  
D J Pullen ◽  
M J Borowitz ◽  
A J Carroll ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Significant Treatment ◽  
Free Survival ◽  
Pediatric Oncology Group ◽  
B Lineage ◽  
To Receive ◽  
Standard Risk

PURPOSE To develop antimetabolite-based consolidation regimens that minimize acute and long-term toxicities and improve the survival rate of children with standard-risk B-lineage acute lymphocytic leukemia (ALL). PATIENTS AND METHODS Seven hundred twenty-seven eligible patients with standard-risk early pre-B ALL were registered onto the study. Seven hundred sixteen patients attained a complete remission (CR) after induction therapy. Of these, 114 patients were randomized to a different regimen and were the subject of a separate report. Six hundred two patients were randomized to receive one the following regimens: intermediate-dose methotrexate (IDMTX) with leucovorin rescue on weeks 7, 10, 13, 16, 19, and 22 (regimen A); regimen A plus asparaginase (ASP) administered intramuscularly (i.m.) weekly for 24 weeks (regimen B); or regimen A plus a 24-hour infusion of cytarabine (AraC) with each IDMTX (regimen C). After consolidation, patients were placed on maintenance therapy through week 156. Regimens A and C were opened in February 1986, and regimen B in May 1987. Comparisons are based on concurrently randomized patients (May 1987 to January 1991 between regimens A and B, and February 1986 to January 1991 between regimens A and C). RESULTS The 5-year continuous CR (CCR) rates were not significantly different: A versus B, 78.1% (3.9 +/- SE) versus 83.3% +/- 3.5% and A versus C, 79.4% +/- 3.2% versus 83.5% +/- 2.9%; P by one-sided log-rank tests were .27 and .34, respectively. Significant treatment differences were not found with regard to sex, rate of testicular and CNS relapse, or CNS complications. During consolidation, regimen C had significantly more bacterial infections (P = .0032) and days spent in the hospital (P < .001) compared with regimen A. CONCLUSION We were unable to show a statistical advantage of adding either ASP or AraC to IDMTX in terms of improvement in event-free survival (EFS).

scholarly journals Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome–negative acute lymphocytic leukemia

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1892-1898 ◽  
Author(s):  
Hui Yang ◽  
Tapan Kadia ◽  
Lianchun Xiao ◽  
Carlos E. Bueso-Ramos ◽  
Koyu Hoshino ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
Aberrant Methylation ◽  
Epigenetic Alterations ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Standard Risk

Pretreatment aberrant DNA methylation patterns are stable at time of relapse in acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual methylation alterations at the time of morphologic remission may predict for worse prognosis. We developed a real-time bisulfite polymerase chain reaction assay and analyzed the methylation levels of p73, p15, and p57KIP2 at the time of initial remission in 199 patients with Philadelphia chromosome-negative and MLL− ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in 33 (17.4%), and p57KIP2 in 7 (3.7%); 140 (74%) patients had methylation of 0 genes and 48 (25%) of more than or equal to 1 gene. In 123 (65%) patients, matched pretreatment samples were also studied and compared with remission ones: in 82 of those with initial aberrant methylation of at least one gene, 59 (72%) had no detectable methylation at remission and 23 (28%) had detectable residual methylation. By multivariate analysis, the presence of residual p73 methylation was associated with a significant shorter duration of first complete remission (hazard ratio = 2.68, P = .003) and overall survival (hazard ratio = 2.69, P = .002). In conclusion, detection of epigenetic alterations allows the identification of patients with ALL with standard risk but with poor prognosis.

Clinical Implication of Bone Marrow Angiogenesis in Childhood Acute Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1455-1455
Author(s):  
Sung Chul Won ◽  
Sun Young Rha ◽  
Seung Hwan Oh ◽  
Hwang Min Kim ◽  
Chuhl Joo Lyu
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
High Risk ◽  
Normal Control ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
The Other ◽  
Enzyme Linked Immunosorbent Assay ◽  
Childhood All ◽  
Standard Risk

Abstract Purpose: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with increased angiogenesis, growth, and metastasis in solid tumors. But, until today, the importance of theses factors on leukemia, especially childhood acute lymphocytic leukemia (ALL) has received limited attention. Therefore, this study examined the bone marrow plasma VEGF and bFGF levels in ALL patients and normal controls. Methods: Bone marrow plasmas at diagnosis from 33 ALL patients (median age 5.97 years; range 1.8–13.9 years) were used for analysis. All ALL patients are divided into 3 groups; one group is standard risk ALL, other group is high risk ALL who did not experience relapse, and the other group is high risk ALL who have experienced relapse during treatment. The bone marrow levels of bFGF and VEGF were determined by enzyme-linked immunosorbent assay (R & D Systems) and compared with the bone marrow levels of 7 healthy control subjects (median age 11.98 years; 6 months–13.6 years). Results: The VEGF levels were higher in high risk ALL with relapse (N=7, 171.95 ± 202.54 pg/mL) compared with standard risk (N=9, 9.11 ± 21.47 pg/mL), high risk ALL without relapse (N=17, 37.09 ± 38.77 pg/mL) or normal control (N=7, 72.9 ± 68.22 pg/mL)(P=0.006). Figure Figure The bFGF levels were also significantly higher in high risk ALL patients who experienced relapse (high risk with relapse; 37.26 ± 35.73 pg/mL, standard risk ALL; 7.90 ± 12.99 pg/mL, high risk ALL without relapse; 7.27 ± 10.93 pg/mL, normal control; 6.39 ± 6.13 pg/mL) (P=0.003). Figure Figure The Pearson correlation coefficient between VEGF and bFGF was 0.775 (P &lt; 0.01). Three patients who showed high levels of both angiogenic markers (VEGF; 366.80 ± 141.29 pg/mL, bFGF; 70.27 ± 5.57 pg/mL) are relapsed and died due to disease progression. The other relapsed patients except these 3 patients are alive without disease after salvage chemotherapy. Conclusion: Our data suggest that the increased levels of VEGF and bFGF in bone marrow may play an important role in estimating prognosis of childhood ALL.

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