Pharmacokinetics and Pharmacodynamics of Oral Etoposide in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (7) ◽  
pp. 1340-1346 ◽  
Author(s):  
Mathew J. Edick ◽  
Amar Gajjar ◽  
Hazem H. Mahmoud ◽  
Matthijs E.C. van de Poll ◽  
Patricia L. Harrison ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Response To Therapy ◽  
Remission Induction ◽  
Pharmacokinetic Data ◽  
Oral Etoposide ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Childhood All

Purpose: To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL). Patients and Methods: Fifty-eight patients were randomly assigned to etoposide at 50 mg/m2/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started. Etoposide pharmacokinetics and pharmacodynamics were studied for 47, 28, and 26 patients on day 1, 8, and 22, respectively, of remission reinduction therapy. Results: Of 48 patients with pharmacokinetic data, 42 (87.5%) achieved complete remission, three (6.3%) failed to achieve remission, and three (6.3%) died during induction. Median etoposide day 8 area under concentration-time curve (AUC) and cumulative AUC tended to be greater (P = .06 and P = .07, respectively) in patients (n = 23) who achieved complete remission (24 and 522 μmol/L • h, respectively) than in patients (n = 3) who did not (14 and 303 μmol/L • h, respectively). Three of eight patients with plasma concentrations exceeding 1.7 μM (1 μg/mL) for more than 8 hours daily, compared with one of 20 patients with concentrations exceeding 1.7 μM for ≤ 8 hours daily, were unable to receive all 22 days of etoposide because of toxicity. There was no difference in the AUC at day 1 or day 8 with once- versus twice-daily doses (P = .55 and P = .86, respectively). Conclusion: A pharmacodynamic relationship exists between systemic etoposide exposure and response to therapy when oral etoposide is used as part of remission induction regimens for relapsed or refractory childhood ALL.

scholarly journals Absence of terminal transferase may predict failure of remission induction in childhood ALL

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 81-84
Author(s):  
SB Shurin ◽  
JJ Scillian
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Glucocorticoid Receptors ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Membrane Receptors ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Remission Induction ◽  
Childhood All ◽  
Adenosine Deaminase Activity

Two children with acute lymphoblastic leukemia (ALL), whose lymphoblasts lacked terminal deoxynucleotidyl transferase (TdT) by both enzyme and fluorescent antibody assay, responded poorly or not at all to vincristine and prednisone. Both patients had high presenting white counts and mixed L1-L2 morphology. Lymphoblasts from one patient, an adolescent boy with a mediastinal mass, possessed surface membrane receptors for sheep red cells (E) and for complement (EAC) and had elevated adenosine deaminase activity (ADA). Lymphoblasts from a 2.5-yr- old boy without a mediastinal mass did not form E or EAC rosettes and did not express the la-like antigen or carry surface immunoglobulin. The poor response to therapy and absence of TdT were associated with a lymphoblast phenotype suggestive of a highly differentiated T-cell- derived line in one instance and an undifferentiated cell in the other instance. It is postulated that absence of TdT may predict poor therapeutic efficacy of vincristine and prednisone in acute lymphoblastic leukemia in childhood. The absence of TdT may correlate with other developmental characteristics of lymphoblasts, such as altered function or low numbers of glucocorticoid receptors or resistance to lysis by steroid drugs. Determination of many parameters of lymphoblast phenotype at diagnosis to characterize the nature of the malignant cells more precisely may ultimately enhance our understanding of, and improve therapy for, the group of leukemic children who fail to respond to standard regimens.

scholarly journals Absence of terminal transferase may predict failure of remission induction in childhood ALL

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 81-84 ◽  
Author(s):  
SB Shurin ◽  
JJ Scillian
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Glucocorticoid Receptors ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Membrane Receptors ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Remission Induction ◽  
Childhood All ◽  
Adenosine Deaminase Activity

Abstract Two children with acute lymphoblastic leukemia (ALL), whose lymphoblasts lacked terminal deoxynucleotidyl transferase (TdT) by both enzyme and fluorescent antibody assay, responded poorly or not at all to vincristine and prednisone. Both patients had high presenting white counts and mixed L1-L2 morphology. Lymphoblasts from one patient, an adolescent boy with a mediastinal mass, possessed surface membrane receptors for sheep red cells (E) and for complement (EAC) and had elevated adenosine deaminase activity (ADA). Lymphoblasts from a 2.5-yr- old boy without a mediastinal mass did not form E or EAC rosettes and did not express the la-like antigen or carry surface immunoglobulin. The poor response to therapy and absence of TdT were associated with a lymphoblast phenotype suggestive of a highly differentiated T-cell- derived line in one instance and an undifferentiated cell in the other instance. It is postulated that absence of TdT may predict poor therapeutic efficacy of vincristine and prednisone in acute lymphoblastic leukemia in childhood. The absence of TdT may correlate with other developmental characteristics of lymphoblasts, such as altered function or low numbers of glucocorticoid receptors or resistance to lysis by steroid drugs. Determination of many parameters of lymphoblast phenotype at diagnosis to characterize the nature of the malignant cells more precisely may ultimately enhance our understanding of, and improve therapy for, the group of leukemic children who fail to respond to standard regimens.

scholarly journals High incidence of potential p53 inactivation in poor outcome childhood acute lymphoblastic leukemia at diagnosis

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1155-1161 ◽  
Author(s):  
DI Marks ◽  
BW Kurz ◽  
MP Link ◽  
E Ng ◽  
JJ Shuster ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Leukemic Cells ◽  
Childhood All ◽  
P53 Gene Mutations ◽  
P53 Inactivation

Previous studies have indicated that p53 gene mutations were an uncommon event in acute lymphoblastic leukemia (ALL) in children. In one series of 330 patients, p53 mutations were seen in fewer than 3%. We analyzed bone marrow mononuclear cells derived from 10 children with ALL at diagnosis who subsequently failed to achieve a complete remission or who developed relapse within 6 months of attaining complete remission for p53 gene mutations and mdm-2 overexpression. We found that three children had p53 gene mutations, and four overexpressed mdm-2. Also, experiments comparing relative levels of mdm- 2 RNA and protein in these patients demonstrated that mdm-2 overexpression can occur at the transcriptional and posttranscriptional level in primary leukemic cells. Although we were unable to link Waf-1 RNA expression with p53 status in childhood ALL, our data show potential p53 inactivation by multiple mechanisms in a large percentage of these patients and demonstrate that these alterations can be detected at diagnosis. Inactivation of the p53 pathway may, therefore, be important in children with ALL who fail to respond to treatment and may be useful for the early identification of children requiring alternative therapies.

Genomic Variants Associated with Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-11-SCI-11
Author(s):  
Mary V. Relling
Keyword(s):  
Genetic Variation ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Drug Clearance ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Pharmacokinetic Data ◽  
Clinical Effects ◽  
Childhood All ◽  
Genome Wide ◽  
A Genome

Abstract Abstract SCI-11 Genome-wide interrogations have a role in addressing both the etiology and the responsiveness of childhood acute lymphoblastic leukemia (ALL). Recent work by our own1 and other groups identified common polymorphisms in ARID5B, and to a lesser extent in IKZF1, as predisposing to the development of childhood ALL. Polymorphisms in these two genes can account for ∼ 40% of the population attributable risk of ALL, and differences in the frequency of the minor allele among different ancestral groups can account for a large portion of the differences in the incidence of ALL among different race groups. The association of these inherited polymorphisms with specific ALL subtypes (e.g. ARID5B with risk of hyperdiploid ALL) indicates that germline polymorphisms affect not only risk of ALL but may also affect or confound association analyses between germline variants and the probability of cure of ALL. The biological basis for the prognostic differences that exist among ALL subtypes remain largely unknown, and it is plausible that inherited polymorphisms may affect both susceptibility to subtypes of ALL as well as to drug responsiveness. Genome-wide analyses have also identified polymorphisms associated with eradication of MRD across multiple treatment protocols.2 Polymorphisms in IL15 indicate variants that likely affect the inherent pharmacodynamic responsiveness of ALL to drug-induced apoptosis. Approximately 20% of the polymorphisms associated with MRD were also associated with rapid drug clearance in the host, even though pharmacokinetic data were only available for 2 of the 4–8 medications used during induction. These findings lead us to suggest that perhaps half of the polymorphisms associated with eradication of ALL are related to effects on host drug clearance, and about half have penetrant effects on the inherent responsiveness of the ALL cells themselves. A genome-wide analysis for the determinants of clearance of one such drug, methotrexate, identified a strong effect of polymorphisms in the SLCO1B1 transporter.3 Genome-wide approaches have identified the importance of genes that decades of candidate gene approaches did not reveal, illustrating the utility of an agnostic approach to genotype-phenotype association studies in childhood ALL. 1. Treviño LR, Yang W, French D, et al. Germline genomic variations associated with childhood acute lymphoblastic leukemia. Nat Genet 41:1001–5, 2009. 2. Yang J, Cheng C, Yang W, et al. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA 301:393–403, 2009. 3. Treviño LR, Shimasaki N, Yang W, et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 27:5972–8, 2009. Disclosures: Relling: St. Jude Children's Research Hospital: Employment, Patents & Royalties; Enzon Pharmaceuticals: Research Funding.

Pentoxifylline During Steroid Window At Induction To Remission Increases Apoptosis In Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2623-2623
Author(s):  
Oscar Gonzalez-Ramella ◽  
Jimenez-Lopez Xochiquetzatl ◽  
Sergio Gallegos-Castorena ◽  
Pablo Ortiz-Lazareno ◽  
Jose Manuel Lerma-Diaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Cancer Cells ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Control Group ◽  
Induction Phase ◽  
Study Group ◽  
Significant Difference

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease. A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy. Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. Methods We included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. Results We enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. Conclusions The present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures: No relevant conflicts of interest to declare.

Experience With BFM 95 Pediatric Regimen In Adult ACUTE Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5015-5015 ◽  
Author(s):  
Hakan Goker ◽  
Eylem Eliacik ◽  
Ayse Isik ◽  
Ibrahim C. Haznedaroglu ◽  
Nilgun Sayinalp ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Adult Acute Lymphoblastic Leukemia ◽  
High Doses ◽  
Dose Reductions

Abstract As treatment of adult acute lymphoblastic leukemia (ALL) is unsatisfactory compared to pediatric disease, there is ongoing interest in the treatment of adult ALL with pediatric regimens. In this context we started to use BFM 95 pediatric regimen (Blood 2008;111:4477) in relapsed adult ALL cases in April 2010 and extended this approach to newly diagnosed non-Burkitt and and non-Ph+ ALL cases aged < 30. Nineteen cases (15 male, 4 female; 11 de novo, 8 relapsed) have been treated during this period in Hacettepe University Med. Ctr. Hematology dept., Ankara, Turkey. Median (range) follow-up durations after BFM 95 regimen and after remission attainment were 4.3 months (1.6-31) and 4.25 (0.4-21.4). Median age was 22 (17-27) in de novo cases and 24 (20-46) in relapsed patients. Three out of 8 relapsed cases had relapsed after allogeneic stem cell transplantation (AlloSCT). Complete remission ratio was 18/19 (95%). One relapsed patient died during induction due to sepsis. The BFM 95 regimen primarily served as a remission induction protocol in relapsed cases. None of these cases completed the treatment protocol. They generally underwent AlloSCT (6 cases) or donor lymphocyte infusion (1 case) shortly after complete remission. Therefore these cases were censored at the time of transplantation in survival analyses. Two out of 11 newly diagnosed patients completed the protocol. In two other cases the treatment was stopped after 2 and 4 consolidation courses for AlloSCT. One de novo patient died in remission. The remaining six de novo cases are still on treatment. Sixteen patients were still alive by the time of last follow-up. Two deaths (during induction and consolidation) and 1 relapse were observed by this time. Median (95% confidence interval) estimated overall and disease-free survival durations were 31 months (not calculable) and 19.4 months (2.6-36.2), respectively. Grade 3-4 non-infectious toxicities were observed only in 5 (%26) patients during treatment. Liver dysfunction, pancreatitis, acute renal failure, and mucositis were occasionally observed. These significant toxicities were due to high doses of methotrexate (5 g/m2) and L-asparaginase (25 000/m2) which were used during early periods of this study. After adequate dose reductions these toxicities were not observed subsequently. Dose reduction for high dose dexamethasone (60 mg/m2) and CMV surveillance were also deemed necessary after one case of fatal CMV reactivation was observed during IIA consolidation protocol. In conclusion, BFM 95 regimen seems to be highly efficacious with a 95% CR rate in young adults. In order to reduce excess toxicities, appropriate dose reductions are necessary for high doses of methotrexate, L-asparaginase and dexamethasone which are applied during various steps of this regimen. However, longer follow-up and more patients and controlled studies are needed in order to reach firm conclusions. Disclosures: No relevant conflicts of interest to declare.

Outcomes of Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia with t(4;11)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4502-4502
Author(s):  
Yuko Sekiya ◽  
Atsushi Narita ◽  
Nao Yoshida ◽  
Kimikazu Matsumoto ◽  
Koji Kato
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Childhood All ◽  
Allogeneic Hsct ◽  
One Year

Abstract Abstract 4502 Introduction: As the prognosis of childhood acute lymphoblastic leukemia (ALL) with t(4;11) is generally poor, hematopoietic stem cell transplantation(HSCT) at 1st complete remission is recommended in most of Japanese ALL protocol. We analyzed outcomes of HSCT for childhood ALL with t(4;11) at our department, and assessed the outcomes with age and preconditioning at HSCT. Subjects: We retrospectively analyzed 15 patients who underwent HSCT between 1991 and 2011. The onset of ALL was less than one year old (infant ALL) in 9 patients and over one year old in 6 patients. The disease status at HSCT was 1st complete remission (CR1) in 10 patients, 2nd complete remission (CR2) in 2 patients, and more advanced stages in 3 patients. 13 patients underwent allogeneic HSCT and 2 patients underwent autologous HSCT at median age of 19 months. In allogeneic HSCT, the number of bone marrow transplantation from HLA matched sibling was 3 and 4 from unrelated donors, and that of cord blood transplantation was 6. Nine patients including 7 infant ALL underwent conventional stem cell transplantation (CST), 6 patients including one infant ALL underwent reduced intensity stem cell transplantation (RIST). Preconditioning of RIST was mostly consisted of fludarabine and melphalan with 3Gy of total body irradiation (TBI). Results: Of all 15 patients, 8 patients are alive in CR. Three out of 9 infant ALL and 5 out of 6 ALL patients, whose onset was above 1 year old, are alive in CR. Seven of 10 ALL patients who underwent HSCT in 1st CR are alive, on the other hand, only one of 5 patients in 2nd CR or non CR is alive. Five patients who underwent RIST over 1 year old are alive in CR. Discussion: HSCT for childhood ALL with t(4;11) in 1st CR could achieve better outcome than those in 2nd CR or non CR. The transplant outcomes with RIST was better than CST and it could be applied for ALL patients with t(4;11) whose onset is over one year old. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Simultaneous changes in expression levels of BAALC and miR-326: a novel prognostic biomarker for childhood ALL

2020 ◽  
Vol 50 (6) ◽  
pp. 671-678 ◽  
Author(s):  
Elaheh Sadat Ghodousi ◽  
Narges Aberuyi ◽  
Soheila Rahgozar
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Line ◽  
In Silico ◽  
Prognostic Biomarker ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Leukemia Cell Line ◽  
Childhood All ◽  
Expression Levels ◽  
Response To Chemotherapy

Abstract Objective Multidrug resistance and consequent relapse are two major obstacles for treating children with acute lymphoblastic leukemia, the most frequent childhood malignancy. MicroRNAs have potential regulatory roles in response to chemotherapy. The goal of this study was to determine the microRNA that may have effects on the expression level of brain and acute lymphoblastic leukemia (BAALC) and to investigate the in vitro and ex vivo association between their expression levels. Methods In silico tools were utilized to determine a putative miRNA targeting BALLC. Quantitative real-time polymerase chain reaction was used to investigate expression levels of BAALC and its predicted microRNA, miR-326, in bone marrow samples of 30 children with acute lymphoblastic leukemia and 13 controls, in addition to the resistant and parental CCRF-CEM cell lines. To assess the status of response to therapy, minimal residual disease was measured using single-strand conformation polymorphism. Results MiR-326 was selected due to the strong possibility of its interaction with BAALC according to the obtained in silico results. Statistical analysis showed a significant downregulation of miR-326 and overexpression of BALLC in drug-resistant acute lymphoblastic leukemia cell line and patients compared with the parental cell line and drug-sensitive patients, respectively (P = 0.015, 0.005, 0.0484 and 0.0005, respectively). The expression profiles of miR-326 and BAALC were inversely correlated (P = 0.028). Conclusions The results introduced the inversely combined expression levels of miR-326 and BAALC as a novel, independent prognostic biomarker for pediatric acute lymphoblastic leukemia (P = 0.007). Moreover, bioinformatics data showed a possible regulatory role for miR-326 on BAALC mRNA, which may possibly contribute to the development of drug resistance in patients with childhood acute lymphoblastic leukemia.

High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group

2006 ◽  
Vol 24 (3) ◽  
pp. 460-466 ◽  
Author(s):  
Masamitsu Yanada ◽  
Jin Takeuchi ◽  
Isamu Sugiura ◽  
Hideki Akiyama ◽  
Noriko Usui ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Short Period

Purpose A novel therapeutic approach is urgently needed for BCR-ABL–positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib. Patients and Methods A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL–positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005. Results Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not. Conclusion Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL–positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.

scholarly journals Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (Protocol 81-01 update)

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2514-2519 ◽  
Author(s):  
CM Niemeyer ◽  
RD Gelber ◽  
NJ Tarbell ◽  
M Donnelly ◽  
LA Clavell ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Low Dose ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Remission Induction ◽  
High Dose ◽  
Childhood All ◽  
To Receive

We evaluated event-free survival (EFS) and leukemia-free interval (LFI) of children treated for acute lymphoblastic leukemia (ALL). Patients were randomized to receive either a low dose or high dose of methotrexate (MTX) as a single agent at the time of diagnosis. Five days later, multidrug therapy was begun. We assessed the early antileukemic efficacy of the two doses of MTX, as well as toxicity and long-term efficacy. An increase in cell kill, as indicated by a larger decrease in the percentage of viable cells in the bone marrow between days 0 and 5, was observed for the high-dose MTX group when compared with the low-dose MTX group (P = .04). At 7.1 years of median follow- up, the 38 children randomized to receive high-dose MTX had a better EFS and LFI compared with the 39 patients randomized to receive low- dose MTX. The 7-year percentages (+/- SE) for EFS were 82% +/- 6% for high-dose MTX and 69% +/- 7% for low-dose MTX (P = .13). The 7-year percentages for LFI were 91% +/- 5% and 69% +/- 7%, respectively (P = .01). We recommend that high-dose MTX be considered as an effective addition to induction therapy in childhood ALL.

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