scholarly journals A method for the detection of abnormal leukocytes using cytochemical criteria.

1981 ◽  
Vol 29 (12) ◽  
pp. 1382-1386
Author(s):  
P Winkel ◽  
T Olesen
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Healthy Subjects ◽  
Lymphoblastic Leukemia ◽  
Cell Number ◽  
Reference Intervals ◽  
Blast Cell ◽  
The Other ◽  
Alarm System ◽  
Cutoff Value ◽  
Blood Specimens

An alarm system for the detection of abnormal leukocytes using off-line data processing of the image of the peroxidase channel oscilloscope picture of the Hemalog-D is presented. The basic idea is that areas on the oscilloscope picture where more than a negligible number of nonpathological leukocytes may be depicted are delimited from the remaining area, which is divided into three alarm zones. The corresponding alarm quantities are the large unstained cells (LUC) or the unstained alarm (UA), the intermediate alarm (IA), and the stained alarm (SA). Reference intervals for these alarms were established using blood specimens from 15 healthy subjects. The system was tested using blood specimens from four patients with acute lymphoblastic leukemia (ALL) and 11 patients with acute myeloblastic leukemia (AML). The UA was the best alarm overall, but for seven of the AML specimens the IA or the SA alarm was superior. The high peroxidase (HPX) and the remainder alarms were inferior to the other alarms. Using the reference mean plus two standard deviations as a cutoff value, the smallest blast cell number fraction detectable by the best alarm was calculated to be smaller than 2% for each of the AML specimens, while it ranged from 7 to 2.9% for the ALL specimens.

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Maha Saleh ◽  
Mohamed Khalil ◽  
Mona S. Abdellateif ◽  
Emad Ebeid ◽  
Eman Z. Kandeel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Count ◽  
Cancer Progression ◽  
Lymphoblastic Leukemia ◽  
Multivariate Logistic Regression Analysis ◽  
Blast Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

scholarly journals Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 166-173 ◽  
Author(s):  
JJ Shuster ◽  
JM Falletta ◽  
DJ Pullen ◽  
WM Crist ◽  
GB Humphrey ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Recursive Partitioning ◽  
Blast Cell ◽  
Recursive Partitioning Analysis ◽  
Important Predictor ◽  
Massive Splenomegaly ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Cell Expression

Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Mature B-Cell Acute Lymphoblastic Leukemia With Associated Translocations (14;18)(q32;q21) and (8;9)(q24;p13)

2003 ◽  
Vol 127 (5) ◽  
pp. 610-613
Author(s):  
Cherie H. Dunphy ◽  
Hendrik W. van Deventer ◽  
Kathryn J. Carder ◽  
Kathleen W. Rao ◽  
Georgette A. Dent
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Review Of The Literature ◽  
Marker Chromosomes ◽  
Cell Acute Lymphoblastic Leukemia

Abstract The translocation t(14;18)(q32;q21) is most commonly associated with follicular lymphoma but has also been described in acute lymphoblastic leukemia (ALL) of B-cell origin. Although these ALL cases have had a pre-pre-B, pre-B, or mature B-cell immunophenotype and L2 or L3 morphology, all have been associated with an abnormality of 8q24. In fact, 91% (10 of 11) have been associated with t(8;22) or t(8;14), marker chromosomes for Burkitt-type ALL. The other case was associated with del(8)(q24). Thus, Burkitt-type ALL may have various immunophenotypes and morphology when associated with t(14;18). We describe a case of mature B-cell ALL associated with t(14;18) and t(8;9)(q24;p13). The morphology was suggestive but not entirely characteristic of the L3 subtype. However, on the basis of the cytogenetic findings and the review of the literature, perhaps this case represents a variant of Burkitt-type ALL, which would be important to recognize for prognostic and therapeutic purposes. We describe our findings and review the literature to heighten awareness of this group of ALLs associated with t(14;18). Additional cases need to be accrued and documented to determine the significance of an associated abnormality of 8q24 in this setting.

scholarly journals Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 166-173 ◽  
Author(s):  
JJ Shuster ◽  
JM Falletta ◽  
DJ Pullen ◽  
WM Crist ◽  
GB Humphrey ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Recursive Partitioning ◽  
Blast Cell ◽  
Recursive Partitioning Analysis ◽  
Important Predictor ◽  
Massive Splenomegaly ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Cell Expression

Abstract Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1036-1040 ◽  
Author(s):  
R Mastrangelo ◽  
R Malandrino ◽  
R Riccardi ◽  
P Longo ◽  
FO Ranelletti ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Glucocorticoid Receptor ◽  
Glucocorticoid Receptors ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
The Other ◽  
Clinical Implications ◽  
Short Term

Abstract We have performed in parallel, in 19 children with acute lymphoblastic leukemia, a quantitative determination of glucocorticoid levels, in vitro steroid induced inhibition of nucleic acid precursors, and a short-term clinical trial of corticosteroids alone, before the treatment was given, which included corticosteroids and other drugs. From our results it appears that high glucocorticoid receptor levels in acute lymphoblastic leukemia of children do not guarantee a clinical response to corticosteroids. On the other hand, glucocorticoid receptors may turn out to be of value in predicting a poor response to corticosteroids only if their levels are considerably low.

New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2543-2549 ◽  
Author(s):  
Nancy R. Schneider ◽  
Andrew J. Carroll ◽  
Jonathan J. Shuster ◽  
D. Jeanette Pullen ◽  
Michael P. Link ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Blast Cell ◽  
Derivative Chromosome ◽  
Oncology Group ◽  
Pediatric Oncology Group ◽  
B Lineage

Abstract To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

Cytokine Gene Polymorphisms in Turkish Patients with Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4441-4441
Author(s):  
Kursat Ozdilli ◽  
Fatma Oguz ◽  
Hulya Bilgen ◽  
Yeliz Duvarci ◽  
Halim Issever ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Control Group ◽  
Target Cells ◽  
Cytokine Gene ◽  
Chi Square ◽  
Other Hand ◽  
Ifn Γ

Abstract Cytokines are chemical mediators between cells and they bind on their own specific receptors on the target cells. Cytokine gene polymorphism may be implicated in the pathogenesis of infections autoimmun disease and malignancies via their effect on cytokine production and regulation. Leukemic cells proliferate under the influence of cytokines. It is known that acute lymphoblastic leukemia (ALL) which is sensitive to some cytokine gene is one of the hematological malignances derived from lymphoid tissue. Our aim is to determined frequencies of selected cytokines (TNF-α, TGF-β, IL-10, IL-6, IFN-γ) in childhood ALL patients and unrelated healthy control groups. We also investigated weather these polymorphism might contribute to the pathogenesis of ALL. Method: Genotyping was performed by polymerase chain reaction with sequence specific primers (PCR-SSP) using “ One lamda” kit in 44 ALL patients and 50 unrelated healthy individuals. Allelic frequencies were determined 24 polymorphism located within 16 cytokine genes. Genotype frequencies between ALL patients and controls were compared using Chi-Square Yates, Fisher’s Exact Tests and Stepwise Logistic Regression Analysis (SLRA). Results: The frequency of TGF-β(TT/GG) allel (29,5% versus 8%, respectively;in chi-square p=0,007,odds ratio=4,82, 95% confidence interval (CI) 1,49–16,16; in SLRA p=0,002, OR=15,26,95% CI 2,77–84,05), TGF-β(TC/GG) allel (36,4% versus 10%, respectively; in chi-square p=0,002,odds ratio=5,14, 95% CI 1,69–15,59; in SLRA p=0,005,OR=10,21, 95% CI 2,02–51,61), IL-6(GC) allel (38,6% versus 8%, respectively; in chi-square p<0,001; odds ratio 7,24; 95% CI 2,20–23,76; in SLRA p=0,02,OR=6,37, 95% CI 1,22–33,15), IL-10(GCC/ATA) allel (36,4% versus 8%, respectively; in chi-square p=0,001, odds ratio 6,57, 95% CI 1,99–21,64; in SLRA p=0,01,OR=8,04, 95% CI 1,40–46,04), IFN-γ(TA) allel (54,5% versus 10%, respectively; in chi-square p<0,001, odds ratio 10,8, 95% CI 3,60–32,40; in SLRA p<0,001,OR=29,43, 95% CI 5,47–158,35) frequencies were found higher in patients with ALL compared to the control group. On the other hand IFN-γ(TT) allel (20% versus 48%, respectively; p=0,005; odds ratio 0,27; 95% CI 0,11–0,70), IFN-γ(AT)(0% versus 22%, respectively; p=0,001; odds ratio 1,28; 95%CI 1,10–1,48; fisher’s exact=0,001) and IL-6(CA)(0% versus 22%, respectively; in chi-square p<0,001; odds ratio 1,28; 95% CI 1,10–1,28; fisher’s exact=0,001) allel frequencies were found higher in the control group compared to the patients with ALL.TNF-α(GG) allel frequency was higher both in patients with ALL and in the control group (72% versus 85%). As a conclusion higher frequency in TGF-b(TT/GG),TGF-b(TC/GG),IL-6(GC), IL-10(GCC/ATA) and IFN-g(TA) allels may predispose to ALL.On the other hand IFN-g(TT), IFN-g(AT) and IL-6(CA) allels might be the preventive factor for ALL The present study is rather significant that it is the study which assessed the relation of the cytokines in patients with ALL compared to the control group taken from the genetic pool of The Turkish population but larger groups of studies must be done in future.

JAK2 mutations and CRLF2 rearrangements in Down Syndrome-Associated Acute Lymphoblastic Leukemia in Japan

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1451-1451
Author(s):  
Isamu Hanada ◽  
Kiminori Terui ◽  
Tsutomu Toki ◽  
Ko Kudo ◽  
Tomohiko Sato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Down Syndrome ◽  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Pseudoautosomal Region ◽  
Rt Pcr ◽  
Childhood All ◽  
Western Countries

Abstract Abstract 1451 Children with Down syndrome (DS) have a 10- to 20-fold increased risk of developing acute lymphoblastic leukemia (ALL). In DS-associated ALL (DS-ALL), the chromosome aberrations which are generally common in childhood ALL, such as hyperdiploidy and t(12;21), are less frequent. Recent studies have shown that activating JAK2 mutations and overexpression of cytokine receptor-like factor 2 (CRLF2) gene are identified in approximately 20% and 50–60% of DS-ALL in Western countries, respectively. Most of the patients with CRLF2 overexpression have been reported to be associated with interstitial deletions of the pseudoautosomal region 1 (PAR1) of the sex chromosomes and the P2RY8-CRLF2 fusion gene. In addition, one report showed that the activating CRLF2 F232C mutation was identified in about 10% of DS-ALL. However, there have been no studies to determine the incidence of these genetic aberrations in Asian patients with DS-ALL. In this study, 23 patients with DS-ALL in Japan were screened for mutations in the pseudokinase domain of the JAK2 gene, the P2RY8-CRLF2 fusion gene, and the CRLF2 F232C mutation by PCR/RT-PCR and direct sequencing. Fourteen patients, whose bone marrow RNAs were available, were also screened for CRLF2 overexpression by real-time quantitative RT-PCR. We identified the JAK2 R683G mutation in 2 patients (9%) and the P2RY8-CRLF2 fusion gene in 4 patients (17%). The CRLF2 F232C mutation was not detected in any patient. CRLF2 overexpression was observed in 2 of 14 patients examined (14%). Although bone marrow RNA was available in only 1 of 4 patients positive for P2RY8-CRLF2, high-level expression of CRLF2 was confirmed in this patient. The other patient with CRLF2 overexpression was negative for P2RY8-CRLF2, indicating the involvement of the other type of CRLF2 rearrangement, IGH@-CRLF2 in this patient. We also performed a preliminary study on JAK1, JAK3, and Interleukin-7 receptor-α (IL7R) mutations, and 14, 11, and 12 patients were screened for mutations in the pseudokinase domain of JAK1, JAK3, and exon 5 and 6 of IL7R, respectively. However, no mutations were identified in any patient. Our results show the lower incidence of CRLF2 rearrangements in DS-ALL patients in Japan than that in Western countries. Gene alterations other than CRLF2 rearrangements may contribute to leukemogenesis in Japanese patients with DS-ALL. To clarify if the incidences of the mutations in JAK1-3, CRLF2, and IL7R are also lower in DS-ALL patients in Japan than those in Western counties, more patients need to be studied. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Capture Sequencing Is a Useful Method for Comprehensive Clonality Analysis Based on Ig/TCR Gene Rearrangements in Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1543-1543
Author(s):  
Dai Nishijima ◽  
Mitsuko Akaihata ◽  
Yuka Iijima-Yamashita ◽  
Tomomi Yamada ◽  
Yuichi Shiraishi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Throughput ◽  
Lymphoblastic Leukemia ◽  
The Other ◽  
Gene Rearrangements ◽  
Clonal Architecture ◽  
Target Capture ◽  
Target Capture Sequencing ◽  
Capture Sequencing

Abstract Introduction Immunoglobulin (Ig)/ T-cell receptor (TCR) gene rearrangements are the most widely used clonal marker to detect residual leukemic cells in patients with Acute Lymphoblastic Leukemia (ALL). Ig/TCR gene rearrangements based molecular minimum residual disease (MRD) monitoring has become one of the most powerful prognostic indicators for patients with ALL. Although the standard method of real-time quantitative PCR (RQ-PCR) provides very good sensitivity in MRD measurement, the workflow is very complicated and time-consuming, requiring expert technique and much work for operation, which limits the number of patients to be examined for MRD monitoring and the number of testable markers per patient. Material and methods To reveal clonal architecture and detect appropriate MRD marker, we designed capture probes covering the coding and recognition signal sequences of V, D, J genes of the Ig/TCR loci. We performed high-throughput target-capture sequencing in 208 pediatric cases with BCP-ALL and 35 pediatric cases with T-cell ALL, including 20 relapsed cases and 14 MRD marker negative cases. Extracted DNA samples were enriched with about 420 capture probes (Agilent Technology) and sequenced by HiSeq2500 platform (Illumina) in order to obtain enough sequence coverage (> 500 mean depth). Sequenced data were analyzed with Ig/TCR recombination analysis tool Vidjil (Giraud et al, 2014) and V(D)J recombination clones were listed according to a number of detected read for each clone. Results Total 2379 clonal Ig/TCR gene rearrangements (median 9 per patient, range 0-82) were detected by capture sequencing among 236 (97%) cases. A clonal IGH sequence with V(D)J recombination was identified in 91% of BCP-ALL cases, followed by TRG (68 %), IGK (67 %), TRA+D (66%), TRD (59 %), TRB (49%), and IGL (15 %), respectively. On the other hand, clonal TRG V(D)J recombination was detected in 74% of T-ALL cases, followed by TRB (69%), TRD (57%), IGH (26%), and TRA+D (6%), respectively. About half of BCP-ALL cases were identified two independent IGH rearrangements. These frequencies agree with previous reports obtained by PCR based experiments. In the cases in this study with well-characterized clonal Ig/TCR gene rearrangements by PCR and Sanger sequencing, our capture sequencing was able to detect all rearrangements used in MRD measurements. Although 8 BCP-ALL cases in this study were marker-negative in standard PCR-MRD diagnostics, clonal Ig/TCR gene rearrangements were identified for 5 out of 8 cases by capture sequencing. Some of the hidden clonal rearrangements showed specific and good quantitative amplification by RQ-PCR and can be used as sensitive PCR-MRD targets. On the other hand, all the MRD marker negative 6 T-ALL cases were not detected clonal Ig/TCR gene rearrangements. Finally, we compared the clonal architecture based on Ig/TCR gene rearrangements between diagnosis and relapse in relapsed B-ALL patients. Changes in the clonal architecture were associated with remission duration. In very early relapse cases, detected Ig/TCR rearrangements and their proportion at relapse are very similar to those at diagnosis. In early to late relapse cases, some major Ig/TCR gene rearrangements were lost at relapse and other minor rearrangements expanded at relapse. Most of the identified Ig/TCR gene rearrangements were different between at diagnosis and at relapse in a case relapsed after more than 10 years. Loss of rearrangements were commonly seen in TRA, TRB, and IgL, while most of the IgK and TRD rearrangements were steady during disease course. Conclusion Introducing target capture sequencing enables to high throughput sample preparation and automated data analysis. Capture sequencing is a useful method for comprehensive detection of Ig/TCR gene rearrangements and contributes to better understanding clonal architecture and detecting appropriate MRD markers in ALL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effectiveness of Dexamethasone compared with Prednisolone in Induction Therapy of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 6 (1) ◽  
pp. 3-9
Author(s):  
Tofazzal Hossain ◽  
MA Mannan ◽  
Shamsoon Nahar ◽  
AKM Amirul Morshed ◽  
Shahnoor Islam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group A ◽  
Bone Marrow Study ◽  
Group B

Background: Corticosteroids are an essential component of treatment for acute lymphoblastic leukemia (ALL). Prednisolone is the most commonly used steroid. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of central nervous system compared with prednisolone.Objectives: To determine the effect of dexamethasone and prednisolone and to compare them in induction therapy of ALL in Children.Material & Methods: A total of 60 newly diagnosed cases of ALL confirmed by bone marrow study, children of either sex with age >1 year were included in this study. Variables studied were age, sex, presenting features, neutrophil count, blast cell count, platelet count, bone marrow status at diagnosis, on D15 & D29 of induction and side effects.Results: Mean age of the patients of group A was 6.28 years & that of group B was 7.2 years. Out of all patients of group A 19 (63.3%) were male and 11 (36.7%) were female. In group B 21 (70.0%) patients were male and rests 9 (30.3%) were female. No statistically significant difference was observed in both groups in terms of age, sex & presenting features. After induction significant difference was observed in liver & spleen size at day 7 and day 15. All patients of both groups had M3 marrow status at diagnosis. Overall, in group A 93.3% patients achieved M1 marrow status (fewer than 5% blasts) and 6.7% had M2 marrow status (5-25% blasts) at day 15 of induction. On the other side 66.7% patients of group B achieved M1 status and 33.3% M2 status at day 15. Statistically significant difference was observed between groups on day 15 in term of achieved marrow status (p<0.05). No statistically significant difference was observed between groups in term of infection in difference days of induction. On day 16 of induction maximum incidence of infection was observed in both groups.Conclusion: Dexamethasone may be an effective alternative option to prednisolone for the treatment of acute lymphoblastic leukemia in children.J. Paediatr. Surg. Bangladesh 6(1): 3-9, 2015 (Jan)

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