Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): Addition of an anthracycline to vincristine and prednisone

1977 ◽  
Vol 3 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Stephen E. Sallan ◽  
Bruce M. Camitta ◽  
Emil Frei Iii ◽  
Lorrie Furman ◽  
Pearl Leavitt ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction

scholarly journals Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia

2018 ◽  
Vol 52 (3) ◽  
pp. 296-306 ◽  
Author(s):  
Vladimir Gasic ◽  
Branka Zukic ◽  
Biljana Stankovic ◽  
Dragana Janic ◽  
Lidija Dokmanovic ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Initial Phase ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Induction Treatment ◽  
Glucocorticoid Response ◽  
Blast Count

AbstractBackgroundResponse to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1,GSTsandABCB1) that could contribute to improvement of GC response through personalization of GC therapy.MethodsRetrospective study enrolling 122 ALL patients was carried out to analyze variants ofNR3C1(rs33389, rs33388 and rs6198),GSTT1(null genotype),GSTM1(null genotype),GSTP1(rs1695 and rs1138272) andABCB1(rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology. The marker of GC response was blast count per microliter of peripheral blood on treatment day 8. We carried out analysis in which cut-off value for GC response was 1000 (according to Berlin-Frankfurt-Munster [BFM] protocol), as well as 100 or 0 blasts per microliter.ResultsCarriers of rareNR3C1rs6198 GG genotype were more likely to have blast count over 1000, than the non-carriers (p = 0.030).NR3C1CAA (rs33389-rs33388-rs6198) haplotype was associated with blast number below 1000 (p = 0.030).GSTP1GC haplotype carriers were more likely to have blast number below 1000 (p = 0.036), below 100 (p = 0.028) and to be blast negative (p = 0.054), whileGSTP1GT haplotype and rs1138272 T allele carriers were more likely to be blasts positive (p = 0.034 and p = 0.024, respectively).ABCB1CGT (rs1128503-rs2032582-rs1045642) haplotype carriers were more likely to be blast positive (p = 0.018).ConclusionsOur results have shown thatNR3C1rs6198 variant andGSTP1rs1695-rs1138272 haplotype are the most promising pharmacogenomic markers of GC response in ALL patients.

scholarly journals Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia

Cancer ◽  
2013 ◽  
Vol 119 (11) ◽  
pp. 2061-2066 ◽  
Author(s):  
Jeffrey E. Rubnitz ◽  
Patrick Campbell ◽  
Yinmei Zhou ◽  
John T. Sandlund ◽  
Sima Jeha ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Prognostic Impact ◽  
Absolute Lymphocyte Counts

Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

1995 ◽  
Vol 13 (10) ◽  
pp. 2490-2496 ◽  
Author(s):  
D P Waber ◽  
N J Tarbell ◽  
D Fairclough ◽  
K Atmore ◽  
R Castro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Verbal Memory ◽  
Lymphoblastic Leukemia ◽  
Cognitive Outcome ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Consistent Finding ◽  
Dose Methotrexate ◽  
Cognitive Sequelae

PURPOSE We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy. PATIENTS AND METHODS Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue. RESULTS There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001). CONCLUSION We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.

scholarly journals Response Adapted Therapy in ETV6/RUNX1-Positive Childhood Acute Lymphoblastic Leukemia Treated per Modified St Jude Total XV Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Mayada Abu Shanap ◽  
Iyad Sultan ◽  
Amal Abu-Ghosh ◽  
Hasan Hashem ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Low Risk ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Standard Risk

Introduction: ETV6-RUNX1 is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a precursor-B phenotype. The presence of ETV6-RUNX1 has been associated with a relatively low rate of relapse in multiple studies. Relapses tend to occur late and have a better salvage rate than other ALL subtypes. Moreover, conflicting data in literature regarding the prognostic significance of ETV6-RUNX1 after accounting for age, initial count and treatment intensity. We sought to study the clinical features, therapy response in newly diagnosed ETV6-RUNX1-positive treated at King Hussein Cancer Center. Methods: Patients were treated per modified St Jude Total (XV) study, risk stratification was further refined by including minimal residual disease (MRD)measurements on day 15 and day 46 of remission induction therapy. Patients with the ETV6- RUNX1 fusion or hyperdiploidy without CNS or testicular disease and a satisfactory early MRD decline (&lt;1% on day 15 and &lt;0.01% on day 46) were classified as being low-risk for relapse and were treated on lower -risk arm regardless of age and leukocyte count. Results: Seventy patients (n=70) with ETV6-RUNX1-positive treated at our institution between May 2006 to October 2017. The median age at diagnosis, 5.8 years (range, 1.5-10.8). ETV6-RUNX1 was associated with favorable age between 1- and 6-years in 55 patients (79%), male gender in 41 patients (59%), initial leukocyte count &lt;10 in 39 patients (56%), CNS status 1 in 100% of patients. The majority, n= 58 (83%) of patients had NCI standard risk (SR) and n=12 (17%) had NCI high risk (HR). Sixty-six patients (94%) had MRD &lt;1% at day 15 and all patients achieved remission with MRD&lt;0.01% at day 46 of remission induction. All patients were treated as LR ALL per modified St Jude total XV protocol. At median follow up of (36 months; range, 26 to 154), in the subgroups of ETV6-RUNX1-positive patients classified as NCI standard risk (SR)and NCI high risk (HR) the 5-year EFS estimates were 94.1% ± 3.2 and 82%±1(P=.13), 5-year OS estimates were 100% and 92% ± 8 (p=0.31) respectively. Conclusion: MRD treatment schema in ETV6/RUNX1 -positive patients have excellent outcomes if they achieved favorable response at day 15 and end of remission induction regardless of the age and Initial leukocyte count. Treatment reduction is feasible and declared safe for children with NCI-HR who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD post remission induction therapy. Disclosures No relevant conflicts of interest to declare.

Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count greater than or equal to 100 x 10(9)/L.

1987 ◽  
Vol 5 (7) ◽  
pp. 1015-1021 ◽  
Author(s):  
G V Dahl ◽  
G K Rivera ◽  
A T Look ◽  
H O Hustu ◽  
D K Kalwinsky ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
First Year ◽  
P 16 ◽  
Continuation Treatment

Childhood acute lymphoblastic leukemia with an initial leukocyte count greater than or equal to 100 X 10(9)/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 X 10(9)/L was 44%, compared with 10% for matched controls (P less than .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.

1993 ◽  
Vol 11 (5) ◽  
pp. 827-833 ◽  
Author(s):  
C Wolfrom ◽  
R Hartmann ◽  
R Fengler ◽  
S Brühmüller ◽  
A Ingwersen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Multicenter Trial ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Median Serum ◽  
Steady State Levels ◽  
Intermediate Dose

PURPOSE Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.

scholarly journals Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia

Blood ◽  
2012 ◽  
Vol 120 (20) ◽  
pp. 4197-4204 ◽  
Author(s):  
Jun J. Yang ◽  
Cheng Cheng ◽  
Meenakshi Devidas ◽  
Xueyuan Cao ◽  
Dario Campana ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Genome Wide ◽  
Minimal Residual ◽  
Risk Of Relapse

Abstract With the use of risk-directed therapy for childhood acute lymphoblastic leukemia (ALL), outcome has improved dramatically in the past 40 years. However, a substantial portion of patients, many of whom have no known risk factors, experience relapse. Taking a genome-wide approach, in the present study, we evaluated the relationships between genotypes at 444 044 single nucleotide polymorphisms (SNPs) with the risk of relapse in 2535 children with newly diagnosed ALL after adjusting for genetic ancestry and treatment regimen. We identified 134 SNPs that were reproducibly associated with ALL relapse. Of 134 relapse SNPs, 133 remained prognostic after adjusting for all known relapse risk factors, including minimal residual disease, and 111 were significant even among patients who were negative for minimal residual disease after remission induction therapy. The C allele at rs7142143 in the PYGL gene was associated with 3.6-fold higher risk of relapse than the T allele (P = 6.7 × 10−9). Fourteen of the 134 relapse SNPs, including variants in PDE4B and ABCB1, were also associated with antileukemic drug pharmacokinetics and/or pharmacodynamics. In the present study, we systematically identified host genetic variations related to treatment outcome of childhood ALL, most of which were prognostic independent of known risk factors for relapse, and some of which also influenced outcome by affecting host dis-position of antileukemic drugs. All trials are registered at www.clinicaltrials.gov or www.cancer.gov (COG P9904: NCT00005585; COG P9905: NCT00005596; COG P9906: NCT00005603; St Jude Total XIIIB: NCI-T93-0101D; and St Jude Total XV: NCT00137111).

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