Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group

Background With advances in supportive and risk-stratified therapy, the 5-year survival rate of acute lymphoblastic leukemia has reached 85.5%. The ALL-2006 treatment protocol was modified and renamed the ALL-2013 protocol, with dose and duration changes. Objective To compare outcomes of the ALL-2006 and ALL-2013 protocols, with regards to mortality, remission, relapse, and three-year survival rates. Methods This was retrospective cohort study. Subjects were acute lymphoblastic leukemia (ALL) patients treated from 2011 to 2018 in Mohamad Hoesin Hospital, Palembang, South Sumatera. The three-year survival rates, relapse, remission rates and comparison of ALL-2006 and ALL-2013 protocols were analyzed with Kaplan-Meier method. Results Mortality was significantly correlated with age at diagnosis <1 year and >10 years, hyperleukocytosis, and high-risk disease status. Patients aged 1 to 10 years, with leukocyte count <50,000/mm3 and standard-risk status had significantly higher likelihood of achieving remission. Mortality was not significantly different between the ALL-2006 protocol group [70.6%; mean survival 1,182.15 (SD 176.89) days] and the ALL-2013 protocol group [72.1%; mean survival 764.23 (SD 63.49) days]; (P=0.209). Remission was achieved in 39.2% of the ALL-2006 group and 33% of the ALL-2013 group (P>0.05). Relapse was also not significantly different between the two groups (ALL-2006: 29.4% vs. ALL-2013: 17.9%; P>0.05). Probability of death in the ALL-2006 group was 0.3 times lower than in the ALL-2013 group (P<0.05), while that of the high-risk group was 3 times higher. Remission was 2.19 times higher in those with leukocyte <50,000/mm3 compared to those with hyperleukocytosis. In addition, relapse was significantly more likely in high-risk patients (HR 2.96; 95%CI 1.22 to 7.19). Overall, the 3-year survival rate was 33%, with 41.7% in the ALL-2006 group and 30.7% in the ALL-2013 group. Conclusion Three-year survival rate of ALL-2006 protocol is higher than that of ALL-2013 protocol but is not statistically significant. Age at diagnosis <1 year and >10 years, hyperleukocytosis, and high-risk group are significantly correlated with higher mortality and lower remission rates. However, these three factors are not significantly different in terms of relapse.

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ANALYSIS OF INDUCTION PHASE GLUCOCORTICOID USE ON ADRENAL SUPPRESSION IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Folia Medica Indonesiana ◽

10.20473/fmi.v52i1.5197 ◽

2017 ◽

Vol 52 (1) ◽

pp. 7

Author(s):

Octaviana Simbolon ◽

Yulistiani Yulistiani ◽

I DG Ugrasena ◽

Mariyatul Qibtiyah

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Adrenal Suppression ◽

Induction Phase ◽

Childhood All ◽

Cortisol Levels ◽

Standard Risk

Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL). However, supraphysiological doses may cause suppression of the adrenal. Adrenal suppression resulting in reduced cortisol response may cause an inadequate host defence against infections, which remains a cause of morbidity and mortality in children with ALL. The occurrence of adrenal suppression before and after glucocorticoid therapy for childhood ALL is unclear. The aim of this study is to analysis the effect of glucocorticoid on cortisol levels during induction phase chemotherapy in children with acute lymphoblastic leukemia. A cross-sectional, observational prospective study was conducted to determine the effect of glucocorticoid on cortisol levels in children with acute lymphoblastic leukemia. Patients who met inclusion criteria were given dexamethasone or prednisone therapy for 49 days according to the 2013 Indonesian Chemotherapy ALL Protocol. Cortisol levels were measured on days 0, 14, 28, 42 and 56 of induction phase chemotherapy. There were 24 children, among 31 children recruited, who suffered from acute lymphoblastic leukemia. Before treatment, the means of cortisol levels were 228.95 ng/ml in standard risk group (prednisone) and 199.67 ng/ml in high risk group (dexamethasone). In standard risk group, the adrenal suppression occurs at about day 56. There was a significant decrement of cortisol levels in high risk group in days 14, 28, 42 against days 0 of induction phase (p=0.001). Both groups displayed different peak cortisol levels after 6 week of induction phase (p=0.028). Dexamethasone resulted in lower cortisol levels than prednisone during induction phase chemotherapy in children with acute lymphoblastic leukemia.

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Treatment Outcome of Discontinued L-Asparaginase in Children with Standard-Risk Acute Lymphoblastic Leukemia: Tokyo Children’s Cancer Study Group (TCCSG) Study L99-15.

Blood ◽

10.1182/blood.v106.11.878.878 ◽

2005 ◽

Vol 106 (11) ◽

pp. 878-878 ◽

Cited By ~ 2

Author(s):

Chitose Ogawa ◽

Akira Ohara ◽

Atsushi Manabe ◽

Ryoji Hanada ◽

Hiroyuki Takahashi ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

Risk Groups ◽

High Risk Group ◽

P Value ◽

Group A ◽

Group B ◽

Standard Risk

Abstract BACKGROUND: L-asparaginase (L-asp) is one of the key drugs in the treatment of acute lymphoblastic leukemia (ALL) in children. However, L-asp often produces severe adverse effects including anaphylaxis resulting in its discontinuation. OBJECTIVE: To evaluate retrospectively the outcome of discontinuation of L-asp in patients with ALL. PATIENTS AND METHODS: Children newly diagnosed as ALL between 1999 and 2003 were consecutively enrolled on the TCCSG L99-15 study. Risk stratification was based on the age, initial white blood cell count, immunophenotype, cytogenetics and the response to prednisolone monotherapy. Totally, 267 (35%) out of 770 children were categorized into a standard-risk group (SR), 317 (41%) into a high-risk group (HR) and 186 (24%) into a very high-risk group (HEX). Allogeneic stem cell transplantation was indicated approximately in 50% of the HEX patients. L-asp was used 9 times in the induction phase in all the risk groups. The total number of L-asp administration all through the treatment was 19 in SR, 20 in HR and at least 10 in HEX. Patients were divided into two groups in the analysis: group A patients who received at least 50% of scheduled doses of L-asp and group B patients who received less than 50%. RESULTS: Remission was obtained in 259 (97%) patients in SR, 311 (98%) in HR and 171(92%) in HEX. In the patients who achieved remission and were analyzed, 195 (83.7%) in SR, 223 (78.8%) in HR and 123 (83.7%) in HEX received all the scheduled doses of L-asp. Event-free survival (EFS) (SE) and overall survival (OS) (SE) at 5 years for all the risk groups are shown in the table. Notably, EFS in group A (92.9%) and in group B (74.1%) in SR was significantly different (p=0.025). CONCLUSION: The outcome in patients who received less than 50% of scheduled dose of L-asp was inferior to that in the patients who received more than 50% of the scheduled dose. This suggests that modification or intensification of the treatment should be considered for the patients who discontinued L-asp in SR. EFS and OS in each group Risk group EFS ± SE(%) OS ± SE(%) (No. in A /B) group A group B p value group A group B p value SR (223 /10) 92.9±2.4 74.1±16.1 0.025 97.8±1.1 88.9±10.5 0.066 HR (269 /14) 78.5±3.2 66.7±19.2 0.969 88.9±2.6 50.0±25.0 0.158 HEX (142 /5) 58.2±5.5 75.5±21.7 0.514 75.6±4.3 80.0±17.9 0.873

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Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

Leukemia ◽

10.1038/leu.2008.52 ◽

2008 ◽

Vol 22 (6) ◽

pp. 1154-1160 ◽

Cited By ~ 25

Author(s):

U Baak ◽

◽

N Gökbuget ◽

H Orawa ◽

S Schwartz ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

High Risk ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Study Group ◽

Cell Acute Lymphoblastic Leukemia

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ANALISIS KADAR KREATININ PADA ANAK DENGAN LEUKEMIA LIMFOBLASTIK AKUT DI PUSAT KANKER ANAK ESTELLA BLU RSUP PROF DR RD KANDOU

e-CliniC ◽

10.35790/ecl.2.1.2014.3662 ◽

2014 ◽

Vol 2 (1) ◽

Author(s):

Fajrul Falakh Tamsil

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Good Effect ◽

Result Show ◽

The Impact ◽

Standard Risk ◽

Common Malignancy

Abstract: Malignant disease in children is one cause of death in the age group of children. Characteristic of the spread and prognosis of malignancy in children is very different with malignancy in adult. Acute Lymphoblastic Leukemia is the most common malignancy in children. Treatment with chemotherapy gifts a good effect in recent years, characterized by a decrease in mortality. How ever, as a vital organ that has function to stabilizer and organ disposal of substances that are not useful and toxic, surely chemotherapy effect on the health of kidney function. The impact of chemotherapy on renal function can be determined by examination of creatinne levels in children undergoing chemotherapy. The purpose of this study is to determine the levels of creatinine in children with acute lymphoblastic leukemia undergoing therapy in Estella Room BLU RSUP Prof Dr RD Kandou Manado. Characteristic of this study is descriptive analytic with retrospectional approach, this case done by taking patient’s medical record data from September 2012-2013. Samples were 30. Conclusion:The result obtained from 30 samples contain as many as 16 samples had normal creatinine levels, and 14 samples had not normal creatinine levels, which consisted of 15 samples with a high risk group, an 15 sample with standard risk group. Bivariat analysis result show the value of P=0.642. From this result, it can be concluded that there is no differences between creatinine levels in children with high risk group and children with standard risk group. Keywords: Acute Lymphoblastic Leukemia, Creatinine, Child Abstrak:Penyakit keganasan pada anak merupakan salah satu penyebab utama kematian pada kelompok umur anak.Kanker pada anak sangat berbeda dengan keganasan pada orang dewasa dalam sifat, penyebaran dan prognosis.Leukimia Limfoblastik Akut merupakan keganasan yang paling sering terjadi pada anak.Penanganan dengan kemoterapi memberikan efek yang baik dalam beberapa tahun terakhir, ditandai dengan penurunan angka mortalitas.Namun sebagai organ vital yang memiliki fungsi sebagai pengatur keseimbangan dan organ pembuangan zat-zat yang tidak berguna serta bersifat toksik, tentunya kemoterapi memberikan efek terhadap kesehatan fungsi ginjal. Dampak kemoterapi terhadap fungsi ginjal dapat diketahui dengan pemeriksaan kadar kreatinin pada anak yang menjalani kemoterapi. Tujuan penelitian ini untuk mengetahui kadar kreatinin pada anak dengan leukemia limfoblastik akut yang menjalani terapi di Ruang Estella BLU RSUP Prof. DR. R.D Kandou.Penelitian ini bersifat deskriptif analitik dengan pendekatan retrospektional, dalam hal ini dilakukan dengan pengambilan data rekam medik pasien sejak September 2012-2013. Sampel berjumlah 30 orang. Simpulan : Hasilyang didapatkan dari 30 orang sampel, terdapat sebanyak 16 sampel yang memiliki kadar kreatinin yang normal, dan 14 sampel yang memiliki kadar kreatinin yang tidak normal, yang terdiri dari 15 sampel dengan kelompok resiko tinggi(High Risk), dan 15 sampel dengan kelompok resiko standar (Standard Risk). Hasil analisis bivariat menunjukkan nilai p=0,642. Dari hasil penelitian ini dapat disimpulkan bahwa tidak adaperbedaan kadar kreatinin pada anak kelompok resiko tinggi (High Risk) LLA, dengan resiko standard (Standard Risk) LLA Kata Kunci: Leukemia Limfoblastik Akut, Kadar Kreatinin, Anak.

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Correlative Study Between Nutritional Status and Remission Outcome in Childhood Acute Lymphoblastic Leukemia in Dr. Soetomo General Hospital Surabaya

Biomolecular and Health Science Journal ◽

10.20473/bhsj.v2i1.12723 ◽

2019 ◽

Vol 2 (1) ◽

pp. 27

Author(s):

Asma' Athifah ◽

Siti Nurul Hidayati ◽

Sulistiawati Sulistiawati

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Nutritional Status ◽

General Hospital ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Childhood Acute Lymphoblastic Leukemia ◽

Induction Phase ◽

Cross Sectional ◽

Term Survival

Introduction: The most common malignancy that is diagnosed in children is acute lymphoblastic leukemia. Undernourished children tend to have poorer long term survival. This descriptive analytic study is aimed towards analyzing the correlation between nutritional status at diagnosis and outcomes of induction phase therapy in childhood acute lymphoblastic leukemia at the Department of Pediatrics Dr. Soetomo General Hospital Surabaya in 2014.Methods: A cross-sectional method using the medical records of patients is used in this study. The nutritional statuses of patients are calculated using weight for length/height trough curves of WHO 2006 or CDC 2000.Results: The results show that from 45 children diagnosed with ALL, 53% are of the age ≤ 5 years old, with 58% males and 42% females. 13% of the patients are in the high risk group and 87% are in the standard risk group. Nutritional statuses of patients are 2% of them obese experienced remission after induction phase therapy, 56% normal with 80% of them experienced remission. 40% underweight with 89% of them experienced remission and 11% not experienced remission, 2% malnutrition and experienced remission. There is no correlation between the nutritional status of children with acute lymphoblastic leukemia with the outcome of induction phase (p = 0.798).Conclusion: In conclusion, there is no correlation between nutritional status and remission outcome of patients with ALL in the induction phase of therapy. However, high percentage of underweight patients shows nutrition needs special attention to improve therapy outcomes.

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Evaluation of VEGF-A in relation to childhood acute lymphoblastic leukemia (in Basrah/Iraq)

Iraqi National Journal of Medicine ◽

10.37319/iqnjm.3.1.4 ◽

2021 ◽

Vol 3 (1) ◽

pp. 39-44

Author(s):

Zainab Badr ◽

Wijdan AL-Moosawi ◽

Sadiq Ali

Keyword(s):

Vascular Endothelial Growth Factor ◽

Acute Lymphoblastic Leukemia ◽

Growth Factor ◽

Risk Group ◽

Lymphoblastic Leukemia ◽

High Risk Group ◽

Childhood Acute Lymphoblastic Leukemia ◽

Healthy Children ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Background: Cancer angiogenesis demonstrates an important role in the progression and pathogenesis of blood malignant disorders including acute lymphoblastic leukemia (ALL). Vascular endothelial growth factor (VEGF)-A is one of the most effective elements of endothelial cell growth; it promotes vascular permeability of endothelial cells and provides the new vasculature with oxygen and nutrients. Higher VEGF-A levels in childhood acute lymphoblastic leukemia (ALL) is associated with poorer patient outcomes. Aim of the study: to assess the level of VEGF-A in plasma of children with ALL. Subject and method: Forty children with ALL and 40 healthy children as control were enrolled in this study conducted at the Oncology Unit in Basrah Children’s Hospital from Oct 2019 to March 2020. Plasma VEGF-A level was evaluated using ELISA assay. Results: The plasma level of VEGF-A is higher in ALL children than those in the control (p < 0.001). Moreover, the plasma VEGF-A level in the high-risk group (HRG) is higher than that in the standard risk group (SRG). Conclusion: The significantly higher level of plasma VEGF-A in ALL children compared to the healthy ones may demonstrate the role of VEGF-A in stimulating angiogenesis in pediatric ALL. Keywords: Angiogenesis, vascular endothelial growth factor-A, childhood acute lymphoblastic leukemia, acute lymphoblastic risk groups.

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