scholarly journals Early Response to Dexamethasone as Prognostic Factor: Result from Indonesian Childhood WK-ALL Protocol in Yogyakarta

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Pudjo H. Widjajanto ◽  
Sutaryo Sutaryo ◽  
Ignatius Purwanto ◽  
Peter M. vd Ven ◽  
Anjo J. P. Veerman
Keyword(s):  
Prognostic Factor ◽  
Low Income ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Early Response ◽  
Added Value ◽  
Response To Treatment ◽  
Intrathecal Methotrexate ◽  
Poor Responders ◽  
Free Survival

Early response to treatment has been shown to be an important prognostic factor of childhood acute lymphoblastic leukemia (ALL) patients in Western studies. We studied this factor in the setting of a low-income province in 165 patients treated on Indonesian WK-ALL-2000 protocol between 1999 and 2006. Poor early response, defined as a peripheral lymphoblasts count of ≥1000/μL after 7 days of oral dexamethasone plus one intrathecal methotrexate (MTX), occurred in 19.4% of the patients. Poor responders showed a higher probability of induction failures compared to good responders (53.1% versus 23.3%,P<0.01), higher probability of resistant disease (15.6% versus 4.5%,P=0.02), shorter disease-free survival (P=0.034; 5-year DFS: 24.9% ± 12.1% versus 48.6% ± 5.7%), and shorter event-free survival (P=0.002; 5-year EFS: 9.7% ± 5.3% versus 26.3% ± 3.8%). We observed that the percentage of poor responders in our setting was higher than reported for Western countries with prednisone or prednisolone as the steroids. The study did not demonstrate a significant additive prognostic value of early response over other known risk factors (age and white blood cell count) for DFS and only a moderately added value for EFS.

scholarly journals High-sensitive basal serum thyroglobulin 6–12 months after thyroid ablation is strongly associated with early response to therapy and event-free survival in patients with low-to-intermediate risk differentiated thyroid carcinomas

2017 ◽  
Vol 176 (5) ◽  
pp. 497-504 ◽  
Author(s):  
P Trimboli ◽  
V Zilioli ◽  
M Imperiali ◽  
L Ceriani ◽  
L Giovanella
Keyword(s):  
Disease Free Survival ◽  
Roc Curves ◽  
Early Response ◽  
Differentiated Thyroid Carcinoma ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Intermediate Risk ◽  
Serum Thyroglobulin ◽  
Free Survival

Objective High-sensitive thyroglobulin assays (hsTg) has decreased the need for stimulated Tg measurements in patients with differentiated thyroid carcinoma (DTC). However, multiple assays analyzing the same samples may report different values. Accordingly, appropriate assay-specific cut-off levels should be selected in representative patient series. Here, we evaluate the role of a new hsTg assay in low-to-intermediate risk DTC patients and select appropriate assay-specific clinical cut-off limits. Design This was a retrospective study. The response to treatment was assessed according to ATA. Methods Patients with low-to-intermediate risk DTC treated and regularly followed-up in our thyroid center. Tg was measured on the Kryptor Compact Plus Instrument (BRAHMS Thermo Fisher Scientific). Results The study series comprised 201 DTC patients and excellent response (ER) was demonstrated in 184 (91.5%). Optimized threshold of basal Tg (onT4-Tg) measured 6–12 months after initial treatment was set by ROC curves analysis at 0.28 ng/mL. Having onT4-Tg <0.28 ng/mL at 6–12 months after treatment was associated with longer disease-free survival of Kaplan–Meier (P < 0.001), ER at early follow-up (odds ratio (OR): 165, P < 0.001) and absence of relapse during follow-up (OR: 328, P = 0.0001). Conclusions Patients with low- and intermediate-risk DTC could be considered cured when they have onT4-Tg levels <0.28 ng/mL coupled with negative imaging at their first post-ablation visit.

scholarly journals Triple Intrathecal Therapy (Methotrexate/Hydrocortisone/Cytarabine) Does Not Improve Disease-Free Survival Versus Intrathecal Methotrexate Alone in Children with High Risk B-Lymphoblastic Leukemia: Results of Children's Oncology Group Study AALL1131

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 35-35 ◽  
Author(s):  
Wanda L. Salzer ◽  
Michael J. Burke ◽  
Meenakshi Devidas ◽  
Lia Gore ◽  
Joanne M. Hilden ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Clinical Signs ◽  
Disease Free Survival ◽  
Intrathecal Methotrexate ◽  
Intrathecal Therapy ◽  
Free Survival ◽  
Prognostic Features ◽  
Post Induction ◽  
Disease Free

Abstract Background: With current multi-agent chemotherapy, 88-90% of children diagnosed with High Risk B-Acute Lymphoblastic Leukemia (HR B-ALL) will be cured. However, for those patients who relapse, ~ 1/3 will have central nervous system (CNS) involvement. Thus, adequate CNS disease control for children with HR B-ALL remains a challenge. AALL1131 was designed to determine if the administration of post-Induction age-adjusted triple intrathecal therapy (ITT) with methotrexate, hydrocortisone, and cytarabine, on a modified augmented Berlin-Frankfurt-Münster (MBFM) backbone, would improve 5-year disease free survival (DFS) of children with HR B-ALL compared to age-adjusted intrathecal methotrexate (IT MTX) alone. Methods: Patients with HR B-ALL included: National Cancer Institute (NCI) HR patients <13 years of age at diagnosis without adverse prognostic features [CNS leukemia at diagnosis (≥ 5 white blood cells in the cerebral spinal fluid with blasts on cytospin and/or clinical signs of CNS leukemia), iAMP21, KMT2A (MLL) rearrangement, or hypodiploidy (<44 chromosomes and/or DNA index <0.81)] who had bone marrow minimal residual disease (BM MRD) <0.01% on Induction day 29; and NCI standard risk (SR) patients lacking favorable cytogenetics (ETV6-RUNX1 fusion or trisomy of chromosomes 4 and 10) who had peripheral blood MRD ≥1% on day 8 and BM MRD <0.01% on Induction day 29, and NCI SR B-ALL patients with favorable cytogenetics who had BM MRD ≥0.01% on Induction day 29. Newly diagnosed children with HR B-ALL were randomized post-Induction in a 1:1 fashion to receive ITT versus IT MTX. A total of 21-26 doses of post-Induction intrathecal therapy was administered during Consolidation (n=4), Interim Maintenance (n=2), Delayed Intensification (n=3), and Maintenance (n=12 for girls, n=16 for boys). Results: The post-Induction HR B-ALL randomization was closed to accrual on March 19, 2018 following planned interim monitoring that revealed a futility boundary was crossed, concluding the inability to show the superiority of ITT compared to IT MTX. Five-year DFS rates for IT MTX versus ITT were 93±3.8% and 90±4.3%, p value=0.86. The corresponding estimated hazard ratio (HR) of IT MTX vs ITT is 1.285; 95% CI of (0.822, 2.01). There were no differences in toxicities observed in patients receiving ITT compared to IT MTX. As such, the study was amended to prescribe IT MTX to all patients. Conclusion: The administration of post-induction age adjusted ITT did not improve 5-year DFS of children with HR B-ALL without CNS leukemia. IT MTX remains the standard of care for CNS prophylaxis. Disclosures Burke: Shire: Speakers Bureau; JAZZ: Speakers Bureau; AMGEN: Speakers Bureau.

scholarly journals Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children’s Oncology Group Study AALL1131

2020 ◽  
Vol 38 (23) ◽  
pp. 2628-2638
Author(s):  
Wanda L. Salzer ◽  
Michael J. Burke ◽  
Meenakshi Devidas ◽  
Yunfeng Dai ◽  
Kristina K. Hardy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Intrathecal Methotrexate ◽  
Oncology Group ◽  
Free Survival ◽  
Oncology Group Study ◽  
Cns Prophylaxis ◽  
Disease Free

PURPOSE The high-risk stratum of Children’s Oncology Group Study AALL1131 was designed to test the hypothesis that postinduction CNS prophylaxis with intrathecal triple therapy (ITT) including methotrexate, hydrocortisone, and cytarabine would improve the postinduction 5-year disease-free survival (DFS) compared with intrathecal methotrexate (IT MTX), when given on a modified augmented Berlin-Frankfurt-Münster backbone. PATIENTS AND METHODS Children with newly diagnosed National Cancer Institute (NCI) high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) or NCI standard-risk B-ALL with defined minimal residual disease thresholds during induction were randomly assigned to receive postinduction IT MTX or ITT. Patients with CNS3-status disease were not eligible. Postinduction IT therapy was given for a total of 21 to 26 doses. Neurocognitive assessments were performed during therapy and during 1 year off therapy. RESULTS Random assignment was closed to accrual in March 2018 after a futility boundary had been crossed, concluding that ITT could not be shown to be superior to IT MTX. The 5-year postinduction DFS and overall survival rates (± SE) of children randomly assigned to IT MTX versus ITT were 93.2% ± 2.1% v 90.6% ± 2.3% ( P = .85), and 96.3% ± 1.5% v 96.7% ± 1.4% ( P = .77), respectively. There were no differences in the cumulative incidence of isolated bone marrow relapse, isolated CNS relapse, or combined bone marrow and CNS relapse rates, or in toxicities observed for patients receiving IT MTX compared with ITT. There were no significant differences in neurocognitive outcomes for patients receiving IT MTX compared with ITT. CONCLUSION Postinduction CNS prophylaxis with ITT did not improve 5-year DFS for children with HR B-ALL. The standard of care for CNS prophylaxis for children with B-ALL and no overt CNS involvement remains IT MTX.

Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial.

1993 ◽  
Vol 11 (3) ◽  
pp. 527-537 ◽  
Author(s):  
D G Tubergen ◽  
G S Gilchrist ◽  
R T O'Brien ◽  
P F Coccia ◽  
H N Sather ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Disease Free Survival ◽  
Cranial Irradiation ◽  
Phase Iii ◽  
Intrathecal Methotrexate ◽  
Free Survival ◽  
Cancer Group ◽  
Drug Induction

PURPOSE The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. PATIENTS AND METHODS Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. RESULTS The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. CONCLUSION Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.

Early response to induction therapy as a predictor of disease-free survival and late recurrence of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

1989 ◽  
Vol 7 (12) ◽  
pp. 1807-1815 ◽  
Author(s):  
D R Miller ◽  
P F Coccia ◽  
W A Bleyer ◽  
J N Lukens ◽  
S E Siegel ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Early Response ◽  
Late Relapse ◽  
Study Group ◽  
Free Survival ◽  
Cancer Study Group ◽  
Prognostic Groups ◽  
Wbc Count ◽  
Disease Free

The Childrens Cancer Study Group (CCSG) CCG-160 protocol series was designed to evaluate prognostic factors in acute lymphoblastic leukemia (ALL). Patients were assigned to one of three prognostic groups based upon initial WBC count and age. To determine the optimal duration of therapy, CCG-160 patients completing 2 years of treatment in continuous remission were randomized ("late randomization") to discontinue therapy or receive another year of maintenance therapy. The prognostic significance of early response to induction therapy, as measured by the percentage of lymphoblasts in the day-14 bone marrow (d14 BM) aspirate, was evaluated in 2,516 children. For 1,490 patients with complete data, the status of the d 14 BM was a highly significant predictor of disease-free survival (DFS) by univariate and multivariate analysis (P less than .0001). The observed/expected (O/E) failure rate in patients with d14 M1 (less than 5% blasts), M2 (4% to 25% blasts), or M3 (greater than 25% blasts) BM rating who were subsequently M1 on day 28 or day 42, was .87, 1.59, and 2.30, respectively (P less than .0001). Patients with M2 or M3 d14 BM were more likely to have L2 ALL (modified French-American-British [FAB] morphologic classification), P less than .001. The significance of the d14 BM rating persisted after correction was made for WBC count and clinical prognostic groups using current CCSG criteria, except in infants less than 12 months of age. The d14 BM was also the most significant predictor of DFS in 975 patients after late randomization at 2 years following diagnosis. The O/E failure rate in patients with d14 M1, M2, or M3 BM was .88, 1.78, and 2.02, respectively (P = .0002, trend). Other significant predictors of late relapse were prognostic groups (P = .0003, trend) and initial WBC count (P = .004, trend). Predictive for both early and late relapse of ALL, early response should be monitored closely and alternative treatment regimens should be considered for slow responders.

scholarly journals Prognostic Value of the Hemoglobin/Red Cell Distribution Width Ratio in Resected Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 710
Author(s):  
Francesco Petrella ◽  
Monica Casiraghi ◽  
Davide Radice ◽  
Andrea Cara ◽  
Gabriele Maffeis ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Disease Free Survival ◽  
Red Cell Distribution Width ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Free Survival ◽  
Node Involvement ◽  
Disease Free

Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. Results: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30–3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33–4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65–23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44–32.2, p < 0.001). Conclusion: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

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