Dikshat Gopal GUPTA ,
Neelam VARMA ,
Shano NASEEM ,
Man Updesh Singh SACHDEVA , Parveen BOSE, Jogeshwar BİNOTA,
Ashish KUMAR , Minakshi GUPTA, Palak RANA, Preeti SONAM,
Pankaj MALHOTRA ,
Amita TREHAN ,
Alka KHADWAL ,
Subhash VARMA
Objective: Based on the immunophenotype, acute lymphoblastic
leukemia (ALL) can be categorized into B-cell or T-cell lineages.
B-cell precursor ALL (BCP-ALL) cases show various genetic/molecular
abnormalities, and varying frequencies of chimeric fusion transcripts
in BCP-ALL cases are reported from different parts of the world. We
studied the immunophenotypic aberrancy profiles of a large number
of BCP-ALL cases with respect to various common chimeric fusion
transcripts.
Materials and Methods: Flow cytometric immunophenotyping and
multiplex reverse-transcription polymerase chain reaction assays were
performed for 986 BCP-ALL cases.
Results: Among 986 BCP-ALL cases, the incidence of various fusion
transcripts was 38.36% in adult cases and 20.68% in pediatric cases.
Adult BCP-ALL patients with t(9;22)(BCR-ABL1) fusion transcripts
and expression of aberrant myeloid markers were significantly older
at presentation (p=0.0218) with male preponderance (p=0.0246)
compared to those without aberrant myeloid expression. In pediatric
patients with the t(12;21)(ETV6-RUNX1) chimeric fusion transcript,
aberrant expression of CD13 was observed in 39.13%, CD33 in
36.95%, and CD117 in 8.69% of patients, respectively. Pediatric BCPALL
patients with the ETV6-RUNX1 fusion transcript and expression of
aberrant myeloid markers were not significantly different compared to
those without with respect to demographic and clinical/hematological
characteristics (p=0.5955). Aberrant myeloid markers were rarely or
never expressed in pediatric and adult BCP-ALL patients with the
t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts.
Conclusion: Aberrant myeloid markers were frequently expressed
among BCP-ALL patients with the t(9;22)(BCR-ABL1) and t(12;21)
(ETV6-RUNX1) fusion transcripts. However, BCP-ALL patients with the t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts
rarely or never expressed aberrant myeloid markers. Aberrant myeloid
CD markers can be used in predicting chimeric fusion transcripts at
baseline so as to plan appropriate tyrosine kinase inhibitor therapy in
cases of BCP-ALL with specific chimeric fusion transcripts. This study
has delineated the relationship of chimeric fusion transcripts with the
aberrant expression of myeloid markers in a large cohort of BCP-ALL
cases.
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Objective: The present study investigated immune disorders and
chemokine C receptor 7 (CCR7) expression in primary immune
thrombocytopenia (ITP) patients and analyzed their changes and
clinical significance before and after treatments.
Materials and Methods: Flow cytometry was used to detect the
proportion of different immune cell subsets in the peripheral blood
of 42 patients with ITP and 20 healthy controls at different time
points. Treatments included first-line drugs, such as glucocorticoids
and intravenous immunoglobulin, and second-line therapy, such as
interleukin-11 and thrombopoietin receptor agonists.
Results: An elevated CD4/CD8 ratio and decreased natural killer (NK)
cells and CD4+CD25+CD127low regulatory T-cells (Tregs) were found in
pretreatment ITP patients compared to healthy controls. The newly
diagnosed group had a higher CD4/CD8 ratio and more NK cells than
the relapsed group. Treg levels of the remission group were higher
than those of the recurrence group. The CD4+CCR7+, CD8+CCR7+, and
CCR7+ subsets of B cells and NK cells showed higher increases in the
newly diagnosed and relapsed group compared to controls and the
remission group. The values for the CD4+CCR7+ and CD8+CCR7+ subsets
in the relapsed group were slightly higher than those in the newly
diagnosed group. The CCR7+ subsets of CD4+ T-cells, CD8+ T-cells, NK
cells, and B cells had lower values in the remission group compared to
the relapsed group. Higher levels of the CD8+CCR7+ subset and lower
levels of NK cells were found in the remission group compared to
the controls. The ratio between the CD4+CCR7+ subset and CD8+CCR7+
subset was lower in ITP patients than in healthy controls. There was
a negative correlation between the CD8+CCR7+ subset and platelet
count in the ITP patients.
Conclusion: ITP patients with CCR7 had immune disorders and high
heterogeneity, and CCR7 was found to be involved in the pathogenesis
of ITP. Further studies are needed to investigate effective treatments
for ITP by targeted regulation of CCR7.
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Melike SEZGİN EVİM ,
Özlem TÜFEKÇİ ,
Birol BAYTAN ,
Hale ÖREN ,
Solmaz ÇELEBİ ,
Beyza ENER ,
Kevser ÜSTÜN ELMAS , Şebnem YILMAZ, Melek ERDEM, Mustafa Kemal HACIMUSTAFAOĞLU,
ADALET MERAL GÜNEŞ
Objective: The incidence of invasive fungal infections (IFIs) has
increased due to intensive chemotherapy in childhood leukemia. The
aim of this study was to evaluate the incidence, risk factors, causative
pathogens, and impact on survival of IFIs among pediatric leukemia
patients.
Materials and Methods: The hospital records of 307 children with
acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia
(AML, n=51), and relapsed leukemia (n=18) between January 2010 and
December 2015 were retrospectively evaluated.
Results: A total of 1213 febrile neutropenia episodes were recorded
and 127 (10.4%) of them were related to an IFI. Of 307 children, 121
(39.4%) developed IFIs. The mean age was significantly older in the IFI
group compared to children without IFIs (p<0.001). IFIs were defined
as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of
the attacks, respectively. Invasive aspergillosis (81.9%) was the most
frequent infection, followed by invasive candidiasis (13.4%) and rare
fungal diseases (4.8%). The majority of IFI attacks in both ALL and
AML occurred during the induction phase. In total, the death rate was
24% and the IFI-related mortality rate was 18%. The mortality rate
among children with IFIs was found to be significantly higher than
that of children without IFIs (p<0.001). Overall and event-free survival
rates at 5 years were also found to be significantly lower in the IFI
group (p<0.001). Relapse (odds ratio: 8.49) was the most effective risk
factor for mortality, followed by developing an IFI episode (odds ratio:
3.2) and AML (odds ratio: 2.33) according to multivariate regression
analysis.
Conclusion: Our data showed that IFIs were more common in older
children. Although proven and probable IFI episodes were more
frequently diagnosed in cases of relapse and AML, children with ALL
and AML had similar frequencies of experiencing at least one episode of IFI. Rare fungal diseases were also identified as a major problem.
Despite success in treatment, IFIs increased the rate of mortality in
children with acute leukemia.
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