scholarly journals COMPARISON OF PERIPHERAL BLOOD ACTIVATED NK CELL PERCENTAGE BEFORE AND AFTER INDUCTION PHASE CHEMOTHERAPY IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (Perbandingan Persentase Sel NK Teraktivasi Darah Tepi Sebelum dan Sesudah Kemoterapi Tahap Induksi di Pasien Leukemia Limfoblastik Akut Anak)

2018 ◽  
Vol 23 (3) ◽  
pp. 281
Author(s):  
Syntia TJ ◽  
Endang Retnowati ◽  
Yetti Hernaningsih ◽  
I Dewa Gede Ugrasena ◽  
Soeprapto Ma’at
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Lymphoblastic Leukemia ◽  
Induction Phase ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Cell Percentage ◽  
Activating Receptors ◽  
Signed Rank ◽  
Before And After

Leukemia Limfoblastik Akut (LLA) adalah keganasan sel progenitor limfoid yang berasal dari sumsum tulang dan ditandai proliferasileukosit. Kejadian LLA masih tinggi, sehingga perlu diteliti peran sel NK dalam melawan leukemia. Tujuan penelitian adalah untukmengetahui perbedaan persentase sel NK teraktivasi sebelum dan sesudah pengobatan induksi dan hubungan persentase sel NK teraktivasisebelum pengobatan induksi dengan keluaran kemoterapi pasien LLA anak. Penelitian analitik observasional dengan rancang banguncohort prospektif. Subjek penelitian 27 pasien di Ruang Rawat Inap Hemato-Onkologi Anak RSUD Dr. Soetomo Surabaya, antara bulanMaret–Juli 2016. Metode memeriksa flowcytometry menggunakan alat BD FACS CaliburTM reagen Fast Immune CD56FITC/CD69PE/CD45 Per CP No.katalog.5055879. Analisis statistik dengan uji Wilcoxon Signed Rank dan regresi logistik. Terdapat perbedaan bermaknarerata persentase sel NK teraktivasi sebelum pengobatan induksi 0,57% (SB 0,53%) dan sesudahnya 2,01% (SB 1,86%) p=0,000.Menunjukkan peningkatan bermakna sel NK teraktivasi sesudah pengobatan induksi. Kenasaban sel NK teraktivasi sebelum pengobataninduksi dengan keluaran kemoterapi berkurangnya gejala penyakit (remisi) dan meninggal R=0.723 berarti kenasabannya kuat.Peningkatan persentase sel NK teraktivasi sesudah pengobatan induksi disebabkan kerja kemoterapi meningkatkan hasil MICA/B dankerja activating receptors sel NK (NKG2D) yang bersifat sitotoksik yang kuat. Persentase sel NK teraktivasi sebelum pengobatan induksiyang rendah disebabkan mekanisme menghilangnya tumor di LLA. Terdapat perbedaan bermakna persentase sel NK teraktivasi sebelumdan sesudah pengobatan induksi. Hasilnya dapat menjadi peramal keberhasilan pemberian kemoterapi LLA anak. Persentase sel NKteraktivasi sebelum kemoterapi tahap induksi yang tinggi berpengaruh kuat terhadap keluaran kemoterapi berkurangnya gejala penyakitdan sebaliknya bila rendah berpengaruh terhadap kemungkinan yang bersangkutan meninggal. Diperlukan hasil jangka panjang sampaiselesai dalam pengelolaan pemberian pengobatan terkait.

scholarly journals COMPARISON OF PERCENTAGE PERIPHERAL BLOOD LYMPHOBLAST PROLIFERATION AND APOPTOSIS IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA BEFORE AND AFTER CHEMOTHERAPY INDUCTION PHASE (Perbandingan Persentase Proliferasi dan Apoptosis Limfoblas di Darah Tepi di Pasien Leukemia Limfoblastik Akut Anak Sebelum dan Sesudah Kemoterapi Tahap Induksi)

2018 ◽  
Vol 23 (3) ◽  
pp. 263
Author(s):  
Farida Nur’Aini ◽  
Endang Retnowati ◽  
Yetti Hernaningsih ◽  
Mia Ratwita A
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Annexin V ◽  
Induction Phase ◽  
Maturation Arrest ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Chemotherapy Induction ◽  
Proliferation And Apoptosis ◽  
Before And After

Leukemia Limfoblastik Akut (LLA) adalah penyakit neoplasma yang dihasilkan dari perpindahan somatik multistep progenitorlimfoid di sumsum tulang, ditandai maturation arrest, proliferasi tidak terkendali seri limfoid serta penumpukan limfoblas di sumsumtulang dan darah tepi. Kelainan terkait aktivitas proliferasi sel berkaitan dengan kendali apoptosis. Penelitian ini bertujuan mengetahuiperbandingan persentase proliferasi dan apoptosis limfoblas di darah tepi pasien LLA anak sebelum dan sesudah kemoterapi tahapinduksi. Subjek penelitian sebesar 12 pasien LLA anak kasus baru yang diperiksa sebelum dan sesudah kemoterapi tahap induksi. Jenispenelitian ini cohort prospektif tanpa pembanding. Pemeriksaan proliferasi limfoblas dilakukan menggunakan spesimen darah tepisedangkan pengecatannya menggunakan reagen PI/RNase. Pemeriksaan apoptosis limfoblas dilakukan menggunakan spesimen darahtepi sedangkan pengecatannya menggunakan reagen FITC Annexin V. Pembacaan proliferasi dan apoptosis limfoblas menggunakan alatBD FACSCallibur dengan metode flow cytometry. Rerata persentase proliferasi dan apoptosis limfoblas sebelum kemoterapi tahap induksi7,84%±7,50 dan 11,50%±8,60 sesudah kemoterapi tahap induksi 3,2%±1,89 dan 13,42%±8,10. Persentase proliferasi limfoblas didarah tepi sesudah pemberian kemoterapi tahap induksi terdapat penurunan bermakna, sedangkan pemeriksaan apoptosis limfoblasdidapatkan peningkatan yang tidak bermakna. Persentase proliferasi limfoblas di darah tepi sesudah kemoterapi tahap induksi terdapatpenurunan bermakna, sehingga dapat dipergunakan sebagai peramal keberhasilan pengobatan pasien LLA anak. Pemeriksaan apoptosislimfoblas tidak terdapat perbedaan bermakna sebelum dan sesudah kemoterapi tahap induksi. Perlu penelitian lebih lanjut untukmenganalisis hasil yang didapat.

Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia

2019 ◽  
Vol 19 (6) ◽  
pp. 564-569 ◽  
Author(s):  
Idoia Martin-Guerrero ◽  
Angela Gutierrez-Camino ◽  
Aizpea Echebarria-Barona ◽  
Itziar Astigarraga ◽  
Nagore Garcia de Andoin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Induction Phase ◽  
Pediatric Acute Lymphoblastic Leukemia

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

Blood ◽  
2014 ◽  
Vol 124 (7) ◽  
pp. 1056-1061 ◽  
Author(s):  
David O’Connor ◽  
Jessica Bate ◽  
Rachel Wade ◽  
Rachel Clack ◽  
Sunita Dhir ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Children With Down Syndrome ◽  
Low Intensity ◽  
Key Points ◽  
Treatment Related Mortality ◽  
Related Mortality

Key Points Infection is the major cause of treatment-related mortality in pediatric acute lymphoblastic leukemia and is greatest during the induction phase. Children with Down syndrome are at high risk for infection-related mortality throughout all treatment phases, including the low-intensity maintenance phase.

scholarly journals NK Cells as Possible Prognostic Factor in Childhood Acute Lymphoblastic Leukemia

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Agnieszka Mizia-Malarz ◽  
Grażyna Sobol-Milejska
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Prognostic Factor ◽  
Nk Cells ◽  
Nk Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Percentage ◽  
Group I ◽  
Group Ii ◽  
Cluster Of Differentiation

Deficiency or impaired function natural killer (NK) cells might result in the development of serious infections and promote the development of malignancies. The aim of our study was to assess the prognostic role of NK cell percentage in bone marrow on the day of acute lymphoblastic leukemia (ALL) diagnosis. 84 children (49 males=58%; median age 5 yrs) with ALL were enrolled. The NK cell percentage was assessed using flow cytometry with antibodies against the cluster of differentiation (CD): CD3, CD56, and CD16. We evaluated two groups: group I (NK+), patients with NK cells in the bone marrow (n=74), and group II (NK-), patients without NK cells in the bone marrow (n=10) (cut-off value of negative <1%). In the patients from group I, the prednisone good response on day 8 and the remission on day 15 of treatment were observed significantly more often (p=.01, p=.03). The children from group I had significantly better survival as compared to those from group II (p=.02) (HR 2.59; 95% CI: 1.38-4.85). The presence of NK cells in the bone marrow at diagnosis can be a prognostic factor in children with ALL. The presented results should be the basis for further research.

Artificial Antigen Presenting Cells (aAPC) Expanded NK-Mediated Enhanced Lysis of Allogeneic Tumor Cells Regardless of HLA Class I/KIR Mismatch and Its Implication of Use in Eradicating Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3023-3023
Author(s):  
Hua Zhang ◽  
Bruce Levine ◽  
Nga Voong ◽  
Alan S. Wayne ◽  
Carl H. June ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Nk Cell ◽  
Lymphoblastic Leukemia ◽  
Target Cells ◽  
Activating Receptors

Abstract Abstract 3023 Poster Board II-999 NK Killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands play critical roles in maintaining natural killer (NK) cell tolerance, while providing surveillance against pathogens and malignant transformation. Natural killer (NK) cells have been explored as tools for adoptive anti-tumor or leukemia immunotherapy and current models hold that a mismatch or absence of KIR ligands on target cells is essential for efficient NK cell mediated cytolysis. However, new approaches are now available to activate NK cells and the role for KIR mediated signaling in regulating cytotoxicity of activated NK cells has not been well studied. In this study, aAPCs comprising IL15Ra+K562 cells engineered to express 4-1BBL activated and expanded peripheral NK cells in the presence of exogenous IL15 up to 1000-fold in 3 weeks. Compared to resting NK cells, 4-1BBL/IL15-activated NK cells upregulated TRAIL and NKp30, 44, 46 expression, and showed significantly enhanced cytotoxicity against a multitude of tumor targets including K562, Daudi, Ewing's tumors, osteosarcoma, as well as autologous tumors (50%-90% killing vs. 0%-8% with non-activated NK cells). Meanwhile we could detect little to no influence of KIR signaling in regulating cytotoxicity by aAPC activated NK cells, since sorted CD158a+ and CD158b+ activated NK cells showed similar killing of tumor cells expressing HLA group C1 (CD158b ligand) and/or C2 (CD158a ligand) antigens. In contrast, killer activating receptors (KARs) were indispensable for the cytolysis of solid pediatric tumors by aAPC-activated NK cells, since the killing was significantly inhibited by fusion proteins binding to the ligands of NKG2D, NK p30, p44, p46, p80 (KARs). About 20-40% inhibition of the killing was accomplished when all four activating receptors were blocked, though other activating receptors have not been well defined. Although acute lymphoblastic leukemia (ALL) blasts were refractory to fresh NK cytotoxicity, 4-1BBL/IL15 activated NK cells demonstrated higher lytic activities (20%-50%) against ALL blasts from either patients or cell lines. ALL blast lysis could be completely or partially inhibited by KAR-blocking fusion proteins, indicating that expression levels of KAR ligands vary among ALL cases and other solid tumors. We conclude that KIR ligand mismatch or absence is not essential for effective NK cytotoxicities on either solid tumors or ALL when fully activated NK cells are utilized. This suggests that adoptive therapy with autologous aAPC-activated NK cells may prove effective in some clinical settings, such as ALL, AML, or certain solid tumors. Further studies to assess the impact of KAR ligand expression on aAPC-activated NK killing of ALL blasts are in progress. Percentage of Activated NK Killings vs. Fresh NK's with/without KAR-Ig Fusion Proteins Activated NK (E:T=2.5:1) Fresh NK (E:T=25:1) -KAR-Ig Fc +KAR-Ig Fc SB tumor (Ewing's) 48% 30% 0.5% HOS (Osteo sarcoma) 63% 36% 0.7% Daudi (B. lymphoma) 78% 46% 0.2% REH (ALL) 54% 8% 3% Disclosures No relevant conflicts of interest to declare.

Peripheral blood lymphocyte recovery and overall survival in pediatric acute lymphoblastic leukemia

2013 ◽  
Vol 61 (1) ◽  
pp. 181-183 ◽  
Author(s):  
Emmanuil Hatzipantelis ◽  
Zoe Dorothea Pana ◽  
Maria Vlachou ◽  
Theodotis Papageorgiou ◽  
Athanassios Tragiannidis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood Lymphocyte ◽  
Peripheral Blood ◽  
Blood Lymphocyte ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia
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