Childhood Acute Leukemia Research Articles

Intensified conditioning regimen with fludarabine combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in children with high-risk acute leukemia

ABSTRACTObjective:Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m2), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen.Methods:A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group).Results:The two-year cumulative incidences of grade II–IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P = 0.029).Conclusion:In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS.

Incidence and Outcome of Childhood Acute Leukemia in A Tertiary Care Hospital of Bangladesh Armed Forces

Background: Worldwide cancer is the second leading cause of death in children under 15 years and acute leukemia is the most prevalent cancer among children.
 Objective: The objective of the study was to analyze the incidence and overall outcome of childhood leukemia patients aged 0-12 years in Combined Military Hospital (CMH), Dhaka.
 Methods: It was a retrospective cross-sectional study. Children below 12 years of age with confirmed diagnosis of leukemia and received treatment from the paediatric oncology unit of department of paediatrics of CMH, Dhaka were taken for this study. Data has been collected from Hospital based cancer registry records from 2011 to 2021. There present status has been collected from regular OPD or by phone calls.
 Results: The commonest cancer was found Acute Leukemia (52%), among them Acute Lymphoblastic Leukemia (ALL) 83.15% and Acute Myeloid Leukemia (AML) 16.85%. Morphological (FAB classification) sub-divisions revealed ALL-L2 (31%) was the commonest group for ALL. In case of AML, AML-M3 (APML) was the commonest (27%). Immunophenotyping of cells revealed Pre-B ALL was the commonest. Cytogenetic analysis revealed ETV6-RUNX1 (21%), t(1;19) ((q23,p13) E2A/PBX1 (11%) were two most common genetic abnormalities found in ALL and t(15;17) (q22;q12) M3,M3v PML-RARA was the commonest cytogenetic abnormalities and (8;21) (q22;q22) RUNX1/RUNX1T1 for AML. In case of ALL overall survival was 54% and in case of AML 40%. About 10% of patients reported relapses.
 Conclusion: Incidence of acute leukemia was the highest among all childhood cancer. At the end of the study, overall survival was 52% of cases, and relapses were seen in 10% of cases.
 DS (Child) H J 2021; 38(1): 17-26

Comparison of bone marrow aspiration and biopsy as diagnostic tool in pediatric age group

Objectives: Bone marrow examination is the final endpoint to the diagnosis of many haematological and nonhaematological disorders when all other clinical diagnostic tools have been done with. It consists of two tests each of which has their own role in making a final diagnosis. First bone marrow aspiration and second bone marrow biopsy. They complement each other and together provides a complete picture of the bone marrow. The study aimed to assess the diagnostic accuracy and to observe the degree of correlation (kappa value) between the two procedures. Material and Methods: This retrospective study was conducted in the department of pathology of our institution from July 2021 to August 2022. In 149 cases, both BMA and BMB was performed simultaneously and was included in the study. BMA slides was stained with Leishman Giemsa stain and BMB underwent tissue decalcification and tissue processing followed by staining with haematoxylin and eosin stain. Other special stains such as PAS, Reticulin and Perl’s, ZielNeelson (ZN) stain were also done on all relevant cases. Data were analyzed using Graphpad Instat 3 and Prism 5. Results: The mean age was 8.23±4.37. Of these, the Male: Female ratio was 1.8:1. The most commonly correlated diagnosis in the lower age group were for iron deficiency anemia (100%), Childhood Acute Leukemia (87.2%) and in higher age groups, the most correlated diagnosis were for Chronic myeloid Leukaemia (100%) and Acute Myeloid Leukaemia (72.72%). Kappa value in our study revealed that there was substantial agreement (0.6295) between the two procedures. the diagnostic efficacy of BMA is 77.18% and for BMB is 90.6%. Conclusion: Bone marrow aspiration and biopsy have upperhand over each other in their respective area. Both shows substantial agreement and hence these should be performed together and not in isolation to give a complete diagnosis.

Hyperleukocytosis in Childhood Acute Leukemia: Early Complications and Survival Outcomes

Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan–Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p < 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%, p < 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively, p = 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia.

Fighting against COVID‐19: Innovations and applications

Fighting against <scp>COVID</scp>‐19: Innovations and applications

Precursor B-cell acute lymphoblastic leukemia presenting with isolated skin relapse: a pediatric case report

BackgroundIn childhood acute lymphocytic leukemia (ALL), relapse is most commonly seen in the bone marrow (10–20%), followed by the central nervous system (3–8%). Isolated skin relapse is very rare in ALL. We report an 8-year-old child presented with isolated skin relapse.Case presentationAn eight-year-old female patient presented with swelling on the scalp 3 months after the completion of the ALLIC-BFM 2009 chemotherapy protocol administered due to the diagnosis of precursor B-cell (pre-B) ALL. Physical examination revealed a hard, painless, hyperemic, nodule-shaped lesion measuring 2 × 1 cm on the right parietal bone. Atypical hematopoietic cells with the prominent nucleolus, narrow cytoplasm, and immunohistochemically stained with CD 10, 19, 22, 79-a, and TdT were observed in the histopathological examination of the skin lesion. There was no blast in the bone marrow aspiration smear and cerebrospinal fluid. The patient was diagnosed with aleukemic leukemia cutis (LC) and pre-B ALL, presenting as an isolated relapse.ConclusionAleukemic LC is a very rare finding after leukemia treatment. It may present with various cutaneous lesions, such as a papule, macule, plaque, nodule, palpable purpura, and ulcerative lesions. Leukemia cutis should be considered in the differential diagnosis of skin lesions developing during or after treatment in children with leukemia.

αβ+ /CD19+ -depleted haploidentical stem cell transplantation for children with acute leukemia: Is there a protective effect of increased γδ+ T-cell content in the graft?

Haploidentical hematopoietic stem cell transplantation (HSCT) with depletion of αβ+ T cells and CD19+ B cells has emerged as a viable alternative to traditional donors for treating acute leukemia in children. As the use of this innovative approach continues to grow and more experience is gained, it is essential to identify and comprehend the key factors that contribute to successful transplantation and improved outcomes. We conducted a retrospective analysis of single-center data from 27 children with acute lymphoblastic leukemia and 11 children with acute myeloid leukemia who underwent haploidentical HSCT with depletion of αβ+ T cells and CD19+ B cells between the years 2013 and 2020. Engraftment was successful in 34 out of 38 patients (90%). The 5-year overall survival and event-free survival rates were 51% and 42%, respectively. There were no cases of grade III-IV acute graft-versus-host disease, and only two patients developed chronic graft-versus-host disease. Patients with a higher content of γδ+ T cells in the graft demonstrated a longer event-free survival. αβ+ /CD19+ -depleted haploidentical hematopoietic stem cell transplantation can offer long-term remission for children with acute leukemia with minimal graft-versus-host disease.

Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.

Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.

Du sang et des larmes par Mohamed Condé

Reviewed by: Du sang et des larmes par Mohamed Condé Deborah Gaensbauer CondÉ, Mohamed. Du sang et des larmes. L'Harmattan, 2022. ISBN 978-2-14-027691-0. Pp. 162. This highly political story of a young boy, Sima, who survives acute childhood leukemia to become a contested leader of a Guinean opposition party, reflects the complexity of the author's syncretic Muslim and Malinke background and his broad involvement as an educator, journalist, and government official in Guinea's turbulent politics. Condé's revised edition of his first published novel augments the meticulous cultural, political, and topographical details that contextualize a very broad spectrum of events and relationships, further enhancing its distinct pedagogical value. The first of the novel's three sections, focalized principally through the perceptions of the seven-year-old Sima's father, Madu, depicts with moving attunement to parental anguish the crucial role of tradition and community in Guinean society. Vacillating between revolt and resignation and ambivalent recourse to spiritualism and herbal remedies as well as mainstream medical practices, Madu struggles for roughly a year to obtain a visa permitting Sima's hospitalization in Paris. Emphasis on the obstacles to Madu's quest posed by bureaucracy in Conakry and distrustful French immigration policies serves to introduce the numerous analyses and critiques of clandestine migration that figure as a primary binding theme in the novel. Intensifying critiques of post-independence Guinea in the second and third sections increasingly inflect the story with a didactic political emphasis. Recovered from leukemia in the second section, thanks to extraordinary familial devotion and combined interventions of traditional African healers and French oncologists, Sima becomes immersed in a community of Guinean expatriates in Paris. Condé relays their dissident conversations at length, mobilizing what is a recurrent and sometimes artistically artificial device to incorporate analyses and background material that would otherwise fall outside the immediate development of the narrative. In the most significant change made to the 2022 edition, Condé eliminates this kind of dramatic tension-breaking elaboration to powerful effect at the end of the novel. Sima, having somewhat naively risked accepting the post of Guinean prime minister, is assassinated just as he believes he is about to succeed in imposing democratic reforms. "La soif du pouvoir de l'homme est plus cruelle que le cancer" (159). This reaction from a witness concludes both editions but with significantly different contextualization. In the first edition, a moralizing commentary on Guinean politics prefaces the remark, clearly distinguishing corrupt government officials from the visionary Sima. In the revised version, the comment is not elaborated. Couched in a fraught ambiguity, it becomes interpretable as a warning generalizable to all political ambitions. The novel's multiple exhortations to young Guineans to resist migration and draw strength from what Condé represents as a uniquely African sense of community are thus complicated by a stark acknowledgement of risks inherent in [End Page 228] fighting for life-sustaining conditions in present-day Guinea. (Between the two versions, Condé was abruptly dismissed from his position as Secretary General of the Ministry of Information and Communication.) Written from a perspective as critical of contemporary Guinea as it is of Western cultural and economic hegemony, Du sang et des larmes is a politically courageous and disturbing portrayal of the fragility of democracy. [End Page 229] Deborah Gaensbauer Regis University (CO), emerita Copyright © 2023 American Association of Teachers of French

Synthesis and biological evaluation of dual MDM2/XIAP inhibitors based on the tetrahydroquinoline scaffold

Overexpression of both human murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP) is detected in tumor cells from several cancer types, including childhood acute leukemia lymphoma (ALL), neuroblastoma (NB), and prostate cancer, and is associated with disease progression and treatment resistance. In this report, we described the design and syntheses of a series of dual MDM2/XIAP inhibitors based on the tetrahydroquinoline scaffold from our previously reported lead compound JW-2-107 and tested their cytotoxicity in a panel of human cancer cell lines. The best compound identified in this study is compound 3e. Western blot analyses demonstrated that treatments with 3e decreased MDM2 and XIAP protein levels and increased expression of p53, resulting in cancer cell growth inhibition and cell death. Furthermore, compound 3e effectively inhibited tumor growth in vivo when tested using a human 22Rv1 prostate cancer xenograft model. Collectively, results in this study strongly suggest that the tetrahydroquinoline scaffold, represented by 3e and our earlier lead compound JW-2-107, has abilities to dual target MDM2 and XIAP and is promising for further preclinical development.

Clinical Presentations of Acute Leukemia in Children’s Cancer Units at Al-Kuwait Hospital, Sana’a City: A Cross-Sectional Study

Clinical Presentations of Acute Leukemia in Children’s Cancer Units at Al-Kuwait Hospital, Sana’a City: A Cross-Sectional Study

Impact of TP53 gene variants on prognosis and survival of childhood acute lymphoblastic leukemia

The tumor suppressor protein 53 (TP53) gene is one of the most studied genes in cancer. Although TP53 variants are rare events in acute leukemia, recent observations showed that relapse samples might harbor TP53 variants. Here, we aimed to determine TP53 variants (hotspot region, exon 4–11) in childhood acute lymphoblastic leukemia (B and T-ALL) patients (n = 94) including diagnostic-relapse pairs (n = 15) by amplicon sequencing and evaluate the clinical impact of these variants. In total, nine different (E298*, R283C, R273H, L252F, C229F, I195T, E286G, c.955_956insC, and c.920-1G > C) variants were identified in 17 (18%) childhood ALL patients. c.(920-1G> C) splice site variant and c.(955_956insC) insertion were reported for the first time. In diagnose-relapse pair samples, we identified acquired and/or loss of TP53 variants in the samples at the time of relapse. TP53 variants were found to be more common in T-ALL (37%) than in B-ALL patients (9%). Pathogenic TP53 variants were associated with a shorter overall survival time (p = 0.001).TP53 variants were found to be associated with inferior outcomes in our cohort and can be an independent risk factor for poor prognosis in childhood acute leukemia patients. Identification of low-frequent variants with next-generation sequencing approaches enables better knowledge of the clonal dynamics of ALL.

Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis.

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.

Phosphorylation stabilized TET1 acts as an oncoprotein and therapeutic target in B cell acute lymphoblastic leukemia.

Although the overall survival rate of B cell acute lymphoblastic leukemia (B-ALL) in childhood is more than 80%, it is merely 30% in refractory/relapsed and adult patients with B-ALL. This demonstrates a need for improved therapy targeting this subgroup of B-ALL. Here, we show that the ten-eleven translocation 1 (TET1) protein, a dioxygenase involved in DNA demethylation, is overexpressed and plays a crucial oncogenic role independent of its catalytic activity in B-ALL. Consistent with its oncogenic role in B-ALL, overexpression of TET1 alone in normal precursor B cells is sufficient to transform the cells and cause B-ALL in mice within 3 to 4 months. We found that TET1 protein is stabilized and overexpressed because of its phosphorylation mediated by protein kinase C epsilon (PRKCE) and ATM serine/threonine kinase (ATM), which are also overexpressed in B-ALL. Mechanistically, TET1 recruits STAT5B to the promoters of CD72 and JCHAIN and promotes their transcription, which in turn promotes B-ALL development. Destabilization of TET1 protein by treatment with PKC or ATM inhibitors (staurosporine or AZD0156; both tested in clinical trials), or by pharmacological targeting of STAT5B, greatly decreases B-ALL cell viability and inhibits B-ALL progression in vitro and in vivo. The combination of AZD0156 with staurosporine or vincristine exhibits a synergistic effect on inhibition of refractory/relapsed B-ALL cell survival and leukemia progression in PDX models. Collectively, our study reveals an oncogenic role of the phosphorylated TET1 protein in B-ALL independent of its catalytic activity and highlights the therapeutic potential of targeting TET1 signaling for the treatment of refractory/relapsed B-ALL.

Quantitative cost‑effectiveness index of cancer treatments.

In spite of advancements being made in technology and treatment strategies, which have markedly improved the survival rate of patients, the cost of cancer care worldwide has increased over the past decades. The presence of several cost-effectiveness ratios has provided significant indexes to assess the balance between cost and effectiveness. However, the currently available indexes still fail to provide a comprehensive and objective evaluation of cancer treatment. Therefore, the present study developed a novel approach, namely a quantitative cost-effectiveness index of cancer treatment, based on the calculation of the hospitalization expense index and efficacy evaluation index. The present study used the data of 16 patients with childhood acute myeloid leukemia who received the high-dose chemotherapy as an example, and the quantitative cost-effectiveness index was used to evaluate the value of this approach. As the increasing prevalence of cancer and the rising cost of pharmaceuticals have contributed to the expenditure, the development of this index may help to solve the current dilemma of cancer treatment and may prove to be essential for the development of an effective approach which may be accessible to and affordable by common persons; thus would then lead to a higher cure rate.

The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency.

Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and function of this gene as a result of germinal mutations underlie distinct clinical presentations, including childhood myelodysplastic syndrome and acute myeloid leukemia, in which the acquisition of additional molecular somatic abnormalities can lead to variable outcomes. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation, which should be performed before irreversible organ damage happens. In this review, we will examine the structural characteristics of the GATA2 gene, its physiological and pathological functions, how GATA2 genetic mutations contribute to myeloid neoplasms, and other potential clinical manifestations. Finally, we will provide an overview of current therapeutic options, including recent transplantation strategies.

Role of maternal diet in the risk of childhood acute leukemia: a systematic review and meta-analysis.

Role of maternal diet in the risk of childhood acute leukemia: a systematic review and meta-analysis.

Highly-sensitive chimerism analysis in blood after allogeneic hematopoietic cell transplantation in childhood leukemia: Results from the Nordic Microchimerism Study

Analysis of chimerism in blood post‐HCT using STR‐PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. Real time quantitative PCR (RQ-PCR) chimerism is 10‐ to 100‐fold more sensitive, but clinical studies in children are sparse. In a prospective multicenter study, we analyzed increasing mixed chimerism (IMC) in blood samples following transplantation for leukemia in 64 children. IMC was defined as a minimum increase of either 0.1% or 0.05% recipient DNA between two samples or a ≥10-fold increase. Samples closer than 30 days to diagnosis of relapse were omitted. The risk of relapse was higher in children with IMC of both 0.1% and 0.05% compared to children without IMC (27.8 (95% CI 4.4-175.8; P&amp;lt;.001), and 18.4 (95% CI 2.8-120.5; P=0.002), respectively). From the date of IMC, the 3-year CI of relapse or MRD-positivity was 26.7% (CI 9.4-47.0) and 18.5% (6.4-35.3) for IMC ≥ 0.1% (n=27) and ≥ 0.05% (n= 40), respectively. In the subset of children without an IMC ≥ 0.1% or ≥ 0.05%, CI of relapse or molecular relapse were 16.7% (5.0 -34.1) and 10.8% (3.4 -23.3), respectively. In all cases with a relapse undetectable by IMC, MRD remained undetectable prior to relapse and standard chimerism negative. In a landmark analysis, neither an IMC ≥ 0.1% nor ≥ 0.05% prior to 90 days post‐HCT was significantly associated with an increased relapse incidence. These results indicate that the serial monitoring of RQ‐PCR chimerism in peripheral blood post-HCT may be a valuable supplement to the minimal residual disease analysis for an early detection of relapse in acute childhood leukemia.

Clinical Characteristics and Prognosis of MLL Rearranged Childhood Acute Lymphocyte Leukemia

The clinical data of 1 414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. The clinical characteristics and efficacy of MLL-r+ and MLL-r- subgroup were compared. The prognostic factors of MLL-r ALL were analyzed by COX regression model. Among all children with ALL, the proportion of patients aged less than 1 year old was 1.8%, and the detection rate of MLL-r+ was 3.4% (48/1 414). The positive detection rate of MLL-r in the age groups <1 year old, and ≥1 year old and ≤14 years old was 38.5% (10/26) and 2.7 (38/1 388), respectively, the difference was statistically significant (P<0.000). Compared with MLL-r- group, the MLL-r+ group had a higher proportion of patients with age <1 year, white blood cell (WBC) count ≥50×109/L, combined central nervous system leukemia (CNSL) and testicular leukemia(TL), while MRD <0.01% on d 33 or d 46 of induction chemotherapy was lower (all P<0.05). The expected 10-year event free survival(EFS) rate and overall survival(OS) rate of the MLL-r+ group were significantly lower than those of the MLL-r- group （EFS： 49.9% vs 77.0%； OS: 55.3% vs 82.9%， P<0.05). COX regression model analysis showed that age <1 year, minimal residual disease (MRD) ≥0.01% on d 33 or d 46 of induction chemotherapy were independent risk factors for worse OS and EFS in MLL-r+ ALL patients (all P<0.05). Age <1 year old, high WBC, concomitant CNSL and TL are more common in children with MLL-r+ ALL at initial diagnosis, with poor early treatment response and long-term prognosis. Age <1 year old at initial diagnosis and MRD positive after induction chemotherapy may be risk factors for poor prognosis.

Molecular Cytogenetics and Immunophenotypic Characterization of Childhood Acute Leukaemia Patients in Tertiary Care Center of Bangladesh – An observative study

Background: Childhood leukemia is genetically a heterogeneous disease. Various types of cytogenetic abnormalities and immunophenotypic character are present in leukaemia which are important for risk stratification, treatment and play as significant prognostic factor. Pediatric acute leukaemia presents with varying clinical, morphological, immunological and molecular characteristics. It is very highly curable if diagnosed and treated properly. For detail typing and subtyping of acute leukemia immunophenotyping and cytogenetics are crucial. The aim of this study was to find out the genetic abnormalities and immunophenotypic characterization of childhood acute leukaemia patients in Bangladesh. Material &amp; Methods: This was a retrospective observational study and was conducted in the Department of pediatric hemato-oncology of Combined Military Hospital, Dhaka and Ahsania Mission Cancer Hospital, Mirpur, Dhaka, Bangladesh during the period from February,2014 to March, 2022. There was total 98 cases of acute leukaemia. Results: In total 98 patients completed the study. We found that 79.59% patients were ALL and 20.41% patients were AML. Among ALL 80.64% were B cell type, 6.40% were T cell Type ; 12.82 % had TEL/AML1 or ETV6/RUNX1 t(12;21)(p13;q22), 5.13% patient had TCF3/PBX1 or E2A/PBX1 t(1;19)(q23;p13). In AML30.00% patient had PML/RARAt(15;17)(q22;q21), 10.00% patient had AML1/ETO or RUNX1/CBFA2T1 t(8;21) (q22;q22), 5.00% patient had FLT3/ ITD. In case of B-ALL highest expression of antigen was CD19 (91.64%) followed by CD10 (80.58%), HLADR (67.94%), CD22 (72.68%), CD79a (72.68%), TdT (52.14%) and CD34 (48.98%). In 44.24% cases there was co-expression of CD10 and CD19 and there was 11.6% expression of myeloid marker CD13 and 1.58% expression of T cell marker CD5. In case of T-ALL there was 100% expression of CD3. Expression of other antigen CD4, CD5, CD7, CD8, CD4/8 co-expression, TdT was 60%. There was 40% expression of CD1a and CD2. There was 20% expression of CD10, CD34 and TCRab also. In case of AML highest expression was MPO (93.75%) followed by CD33 (87.50%), CD13 (81.25%), CD117 (75%), HLADR (43.75%) and CD64 (50%). There was 6.25% aberrant expression of B-ALL marker CD19 and T-ALL marker CD3, CD4, CD5, CD7 also. Conclusion: Depending on this study we can say that except few variations distribution of immunophenotypical subtypes and genetic abnormalities of childhood acute leukaemia are almost similar to other literature published from neighboring countries.This study will serve as a guideline for future study in our country in this aspect.