No Advantage of Dexamethasone Over Prednisolone for the Outcome of Standard- and Intermediate-Risk Childhood Acute Lymphoblastic Leukemia in the Tokyo Children's Cancer Study Group L95-14 Protocol

Purpose To evaluate whether dexamethasone (DEXA) yields a better outcome than prednisolone (PRED) in a prospective, randomized, controlled trial for the treatment of childhood acute lymphoblastic leukemia (ALL). Patients and Methods Two hundred thirty-one standard-risk (SR) patients and 128 intermediate-risk (IR) non–B-cell ALL patients were registered from March 1995 to March 1999. After random assignment in each group, the PRED arm patients received PRED 60 mg/m2 during induction followed by PRED 40 mg/m2 over four intensifications in the SR group and three intensifications in the IR group. DEXA arm patients received DEXA 8 mg/m2 during induction and DEXA 6 mg/m2 during the intensifications. The maintenance phase was continued until week 104. Results Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1% ± 3.9% (n = 117) and 84.4% ± 5.2% (n = 114), respectively, in the SR group (P = .217) and 84.9% ± 4.6% (n = 62) and 80.4% ± 5.1% (n = 66), respectively, in the IR group (P = .625). The primary reason for treatment failure was marrow relapse. Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm. Although complications were more prevalent in the DEXA arm than in the PRED arm, fatal toxicity was rare both groups. Conclusion DEXA administered at 8 mg/m2 during induction and 6 mg/m2 during intensification showed no advantage over PRED administered at 60 mg/m2 during induction and 40 mg/m2 during intensification in both the SR and IR groups.

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Early Evaluation of Bone Marrow Minimal Residual Disease by Flowcytometry on Day 15 Is Feasible on a Multicenter Basis and Bears Strong Prognostic Value in Childhood Acute Lymphoblastic Leukemia. The AIEOP-BFM Experience.

Blood ◽

10.1182/blood.v110.11.1423.1423 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1423-1423

Author(s):

Giuseppe Basso ◽

Giuseppe Gaipa ◽

Maria Grazia Valsecchi ◽

Marinella Veltroni ◽

Michael Dworzak ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Childhood Acute Lymphoblastic Leukemia ◽

Reference Laboratory ◽

Intermediate Risk ◽

Early Measurement ◽

Relapse Risk ◽

Standard Risk ◽

Risk Of Relapse

Abstract Early measurement of blast clearance is a relevant prognostic indicator in childhood acute lymphoblastic leukemia (ALL). To this purpose we measured, by four-colour flowcytometry (FC), the percentage of blast cells in bone marrow samples from Italian patients enrolled in the multicentre AIEOP-BFM ALL 2000 trial. Samples were collected on day 15 (after 14 days of steroids, and one dose of IT-MTX, vincristine, daunorubicine, asparaginase) and shipped overnight to the reference laboratory. The data were compared to PCR-MRD performed, by study design, on day +33 and +78 BM samples. We report the results of patients enrolled between December 2000 and October 2004. The 561 patients studied were not different from the remaining ones (with no available material) including their cumulative incidence of relapse (SE): 17.3% (1.9) vs. 18.1% (1.5) in 850 patients not studied. According to the results of FC-MRD, 5 groups were defined: negative (blast count <0.01%, n=143), <0.1% (n=94), <1% (n=149), 1–10% (n=119), >10% (n=56). Their cumulative 5-year risk of relapse was: 4.1% (1.9), 9.3% (4.0), 14.3% (3.2), 26.5% (5.5), 53.7% (7.4), respectively. By PCR-MRD, the same patients were stratified as follows: 177 were standard risk and had 5-year risk of relapse of 4.1% (1.7), 233 at intermediate risk had a relapse risk of 24.2% (3.4), 37 at high risk had a relapse risk of 58.1% (9); the remaining 124 patients (21.6%) were not stratified by PCR-MRD due to lack of 2 sensitive (≥10−4) markers. Of 177 patients classified as standard risk by PCR (double negative), 110 fell within the 2 subgroups with lower FC-MRD (<0.1%), 46 had <1%, 19 had <10%, only 2 >10% of blasts. Of the 233 patients stratified as PCR-MRD intermediate risk (d78 <10−3), FC-MRD related groups had the following probabilities of EFS: 93.5% (3.6; n=47), 83.3%(8.0; n=30), 80.5%(5.1; n=70), 66.5%(10.8; n=57), 39.2%(11.8; n=29). We conclude that very early measurement of FC-MRD on day 15 bone marrow is feasible in our multicentre cooperative setting. On the basis of our data we suggest the following risk groups: standard, when <0.1% blasts on day 15 BM; intermediate for 0.1 to <10%; high, for >10% blasts. These groups had a risk of relapse of 6.2% (1.9), 19.5% (3), and 53.7% (7.4), respectively. Since it is fast, reproducible, relatively cheap and applicable to virtually all patients, our group decided to apply it prospectively on all ALL patients to integrate PCR-based stratification. Our findings showed that: early (d15) MRD detection by FCM identifies different patients than PCR on d33 and d78; FCM may be very useful to identify earlier the highly sensitive ALL with low relapse risk (even though long-term follow-up is still missing), whereas later timepoints may be accessible for PCR and the identification of HR patients.

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Pediatric-Based Versus Adult Treatment Protocols in Young Adults (18-40 years) with Standard Risk Acute Lymphoblastic Leukemia: The BC Cancer Agency Experience

Blood ◽

10.1182/blood.v126.23.3770.3770 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3770-3770 ◽

Cited By ~ 2

Author(s):

David Simon Kliman ◽

Michael J Barnett ◽

Raewyn Broady ◽

Donna L. Forrest ◽

Alina S. Gerrie ◽

...

Keyword(s):

British Columbia ◽

Overall Survival ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

High Dose ◽

Event Free Survival ◽

Free Survival ◽

Small Cohort ◽

Standard Risk

Abstract Introduction In recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger. The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger. We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity. Methods A retrospective analysis was performed on patients treated for ALL on a pediatric-based protocol. These protocols (ALL 08-01 and ALL 13-01) were modifications of the Donna Farber Cancer Institute 01-175 protocol. The format included induction with high dose methotrexate, followed by central nervous system (CNS) therapy including cranial irradiation. A single cycle of etoposide and high-dose cytarabine was given. Consolidation and continuation cycles included doxorubicin, asparaginase, vincristine and dexamethasone. Patients were included if they were aged 18-40 years and had standard risk, Philadelphia chromosome negative ALL. Between February 2008 and November 2014, 25 eligible patients were identified. These were compared with the 23 consecutive standard risk patients most recently treated with ALL 89-1. They had been diagnosed between February 2003 and July 2008. Exclusion criteria were age greater than 40 and non-standard risk ALL. Demographic and clinical data were collected on all patients from the Leukemia Program databases. Overall survival (OS) was calculated from time of diagnosis until death. Event free survival (EFS) was calculated from diagnosis until death, induction failure or relapse. Estimation of OS and EFS was performed using the Kaplan-Meier method. Patient characteristics were compared using Chi-squared test or Fisher's exact test. Ethics approval was obtained from the University of British Columbia ethics board. Results The median age of the combined patient group was 24.5 years. There were no statistically significant differences pre-treatment between groups. Combined median follow up was 28.7 months All 25 patients receiving a pediatric protocol achieved a CR, compared to 19 of 22 with the adult protocol. Despite the more intense chemotherapy dosing regimen in the pediatric protocol, there was no increase in hospitalizations, invasive fungal infections or deaths from treatment toxicity (Table 1). There was a trend towards increased thrombotic events in the pediatric-treated group, at 32% versus 9%. These included deep vein thrombosis in 4 patients, pulmonary emboli in 2, and cerebral sinus thrombosis in 2. Relapse occurred in 24% of the pediatric-treated patients and 45% of the adult-treated ones (p=0.215). Allogeneic stem cell transplantation was performed in 4 patients in the former group and 7 in the latter. Nine of these were carried out in CR2 or later, with two patients going into transplant with active disease. Overall survival following transplant was 44%. Two year event free survival was significantly improved in the group treated on the pediatric protocol (Figure 1), at 79% versus 36% (p=0.011). There was a trend towards improved overall survival in this small cohort, at 83% versus 49% (Figure 2). Conclusions A pediatric-based ALL treatment protocol was tolerated in patients up to the age of 40 years. In our centre, this is associated with an increase in EFS, and a trend towards increased OS, even considering the small cohort. We await with interest the results of larger studies investigating the ideal upfront therapy for young patients with ALL. Table 1. Results All Patients N=47 Adult N=22 Pediatric N=25 P Number % Number % Number % CR after induction 44 of 47 94 19 of 22 86 25 of 25 100 .095 Severe infection 20 of 47 43 9 of 22 41 11 of 25 44 .831 Thrombosis 10 of 47 21 2 of 22 9 8 of 25 32 .079 Pancreatitis 2 of 47 4 0 of 22 0 2 of 25 8 .491 Toxicity deaths 3 of 47 6 2 of 22 9 1 of 25 4 .593 Relapse 16 of 47 34 10 of 22 45 6 of 25 24 .215 AlloHSCT 11 of 47 23 7 of 22 32 4 of 25 16 .303 Disclosures No relevant conflicts of interest to declare.

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Intensive Chemotherapy for Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Intercontinental Trial ALL IC-BFM 2002

Journal of Clinical Oncology ◽

10.1200/jco.2013.48.6522 ◽

2014 ◽

Vol 32 (3) ◽

pp. 174-184 ◽

Cited By ~ 127

Author(s):

Jan Stary ◽

Martin Zimmermann ◽

Myriam Campbell ◽

Luis Castillo ◽

Eduardo Dibar ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Standard Treatment ◽

Lymphoblastic Leukemia ◽

Risk Groups ◽

Childhood Acute Lymphoblastic Leukemia ◽

Event Free Survival ◽

Free Survival ◽

Early Treatment Response ◽

The Impact ◽

Standard Risk

Purpose From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. Patients and Methods For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). Results At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. Conclusion The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.

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Effect of Protracted High-Dose l-Asparaginase Given as a Second Exposure in a Berlin-Frankfurt-Münster–Based Treatment: Results of the Randomized 9102 Intermediate-Risk Childhood Acute Lymphoblastic Leukemia Study—A Report From the Associazione Italiana Ematologia Oncologia Pediatrica

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.5.1297 ◽

2001 ◽

Vol 19 (5) ◽

pp. 1297-1303 ◽

Cited By ~ 40

Author(s):

C. Rizzari ◽

M.G. Valsecchi ◽

M. Aricò ◽

V. Conter ◽

A. Testi ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Randomized Study ◽

Disease Free Survival ◽

Experimental Treatment ◽

Childhood Acute Lymphoblastic Leukemia ◽

High Dose ◽

Intermediate Risk ◽

Free Survival ◽

Significant Difference

PURPOSE: To assess in a randomized study the therapeutic effect of the addition of high-dose l-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)–based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m2 repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi l-asparaginase product. RESULTS: Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P = .64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.

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CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study

Blood ◽

10.1182/blood.v88.11.4288.4288 ◽

1996 ◽

Vol 88 (11) ◽

pp. 4288-4295 ◽

Cited By ~ 3

Author(s):

FM Uckun ◽

PG Steinherz ◽

H Sather ◽

M Trigg ◽

D Arthur ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

Leukemic Cells ◽

Event Free Survival ◽

Free Survival ◽

Cancer Group ◽

Standard Risk

Abstract We examined the prognostic impact of CD2 antigen expression for 651 patients with T-lineage acute lymphoblastic leukemia (ALL), who were enrolled in front-line Childrens Cancer Group treatment studies between 1983 and 1994. There was a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) (P = .0003 and P = .002, log-rank tests for linear trend). When compared with patients with the highest CD2 expression level (> 75% positivity), the life table relative event rate (RER) was 1.22 for patients with intermediate range CD2 expression level (30% to 75% positivity) and 1.81 for “CD2-negative” patients (< 30% positivity). At 6 years postdiagnosis, the EFS estimates for the three CD2 expression groups (low positivity to high positivity) were 52.8%, 65.5%, and 71.9%, respectively. CD2 expression remained a significant predictor of EFS after adjustment for the effects of other covariates by multivariate regression, with a RER of 1.47 for CD2- negative patients (P = .04). Analysis of T-lineage ALL patients shows a significant separation in EFS after adjustment for the National Cancer Institute (NCI) age and white blood cell (WBC) criteria for standard and high-risk ALL (P = .002, RER = 1.67). The determination of CD2 expression on leukemic cells helped identify patients with the better and poorer prognoses in both of these risk group subsets. For standard risk T-lineage ALL, CD2-negative patients had a worse outcome (P = .0007, RER = 2.92) with an estimated 5-year EFS of 55.9% as compared with 78.3% for the CD2-positive patients. Thus, CD2 negativity in standard risk T-lineage ALL identified a group of patients who had a worse outcome than high-risk T-lineage ALL patients who were CD2 positive. The percentage of CD2 antigen positive leukemic cells from T- lineage ALL patients is a powerful predictor of EFS after chemotherapy. This prognostic relationship is the first instance in which a biological marker in T-lineage ALL has been unequivocally linked to treatment outcome.

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Prospective Analysis of TEL Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2007.14.3552 ◽

2008 ◽

Vol 26 (13) ◽

pp. 2186-2191 ◽

Cited By ~ 53

Author(s):

Jeffrey E. Rubnitz ◽

David Wichlan ◽

Meenakshi Devidas ◽

Jonathan Shuster ◽

Stephen B. Linda ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Prognostic Significance ◽

Oncology Group ◽

Free Survival ◽

Pediatric Oncology Group ◽

Gene Status ◽

Group Sex ◽

Cure Rates ◽

Standard Risk

Purpose To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL). Patients and Methods TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years. Results Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (± SE) for patients with TEL rearrangements was 86% ± 2%, compared with 72% ± 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002). Conclusion We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.

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

Blood ◽

10.1182/blood-2020-142754 ◽

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 (<1% on day 15 and <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 <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 <1% at day 15 and all patients achieved remission with MRD<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.

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Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia.

Revista de la Facultad de Medicina ◽

10.15446/revfacmed.v64n3.53961 ◽

2016 ◽

Vol 64 (3) ◽

pp. 417 ◽

Cited By ~ 1

Author(s):

Angela Maria Trujillo ◽

Adriana Linares Ballesteros ◽

Isabel Cristina Sarmiento

Keyword(s):

Overall Survival ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

Developed Countries ◽

Event Free Survival ◽

Free Survival ◽

Grade 3 ◽

Treatment Abandonment ◽

Cancer In Children

Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment.Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature.Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014.Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively.Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications.

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Causes of Death in Childhood Acute Lymphoblastic Leukemia at Hue Central Hospital for 10 Years (2008-2018)

Global Pediatric Health ◽

10.1177/2333794x20901930 ◽

2020 ◽

Vol 7 ◽

pp. 2333794X2090193

Author(s):

Tran Kiem Hao ◽

Pham Nhu Hiep ◽

Nguyen Thi Kim Hoa ◽

Chau Van Ha

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Maintenance Phase ◽

Childhood Acute Lymphoblastic Leukemia ◽

Induction Phase ◽

Central Hospital ◽

Female Ratio ◽

Cancer Group ◽

Almost All ◽

And Control

Aim. To analyze the common cause of death in childhood acute lymphoblastic leukemia patients. Methods and Materials. A retrospective descriptive study on children with acute lymphoblastic leukemia who died at Hue Central Hospital between 2008 and 2018. All the patients were treated with the same protocol of modified Children’s Cancer Group 1882 and 1881. Results. A total of 238 children with acute lymphoblastic leukemia who were cared for at our center were enrolled. Of these, there were 74 deaths. Among the death group, the male-to-female ratio was 2.7:1. Twenty-six (35.1%) occurred in maintenance phase, 18 (24.3%) occurred in induction phase, and 9 (12.2%) occurred in delayed intensification. Infection was responsible for deaths in 32 of 74 (43.2%) cases. Pseudomonas aeruginosa was found in 3 of 32 infected cases (9.4%) and resistance to almost all antibiotics in our hospital. Relapse, abandonment, and bleeding were documented in 20 (27.0%), 7 (9.5%), and 6 (8.1%) cases, respectively. Twenty-seven (84.3%) patients had absolute neutrophil count <500/µL. Of 32 infectious deaths, pneumonia occurred in 40.6%. Regarding 20 relapse death, bone marrow was the major site of relapse and it occurred in 13 (65%) cases. And there were 65% patients with very early relapse. Conclusions. Infection is the major cause of mortality in acute lymphoblastic leukemia patients in our study. To improve outcome, we should improve supportive care, especially prevention and control infection.

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Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.3.520 ◽

1993 ◽

Vol 11 (3) ◽

pp. 520-526 ◽

Cited By ~ 110

Author(s):

D G Tubergen ◽

G S Gilchrist ◽

R T O'Brien ◽

P F Coccia ◽

H N Sather ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Survival Rate ◽

Systemic Therapy ◽

Lymphoblastic Leukemia ◽

Intrathecal Methotrexate ◽

Intermediate Risk ◽

Relapse Free Survival ◽

Free Survival ◽

Cancer Group ◽

Cns Relapse

PURPOSE This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.

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