A case report of pediatric acute lymphoblastic leukemia with e8a2 BCR/ABL1 fusion transcript.

BACKGROUND: Acute lymphoblastic leukemia is the most common type of cancer in children. Most often it affects the age group between 2 and 5 years of age. Studies have shown an improvement in general survivability, more than 90% 5-year overall survival (OS). Current treatment protocols for acute lymphoblastic leukemia require verification of the presence of favorable and unfavorable genetic abnormalities, which help qualify patients to the appropriate risk group and select a more suitable treatment. The presence of the BCR/ABL1 fusion gene stratifies the patient into a high-risk group and requires special treatment with tyrosine kinase inhibitors (TKI). The three dominant mRNA transcripts are e1a2, e13a2, and e14a2. Nevertheless, cases of atypical BCR/ABL1 transcripts have also been reported. CASE PRESENTATION: This paper presents the case of a pediatric patient with Ph + B-cell precursor acute lymphoblastic leukemia with rare atypical e8a2 BCR/ABL1 fusion transcript. Our patient achieved complete remission after 33 days of treatment. Molecular and cytogenetic studies in TP1 did not reveal the presence of the BCR/ABL1 transcript. The PCR-MRD test in TP1b was negative, the patient did not require hematopoietic stem cell transplantation. CONCLUSION: Genetic evaluation of the bone marrow sample is crucial in the initial stage of the diagnosis. Fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction with Sanger sequencing are the appropriate methods used in the detection of rare variants of BCR/ABL1 transcripts.

Intrachromosomal Amplification of Chromosome 21 in Childhood Acute Lymphoblastic Leukemia: Study of 3 Cases.

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. The presence or absence of a characteristic genetic abnormality usually observed in childhood ALL plays a very important role in determining the prognosis and stratification for treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) is an uncommon high-risk chromosomal abnormality than can occur only in 2% of childhood B-cell precursor lymphoblastic leukemia. Molecular genetic analysis and the fluorescence in situ hybridization (FISH) technique are the basic methods used to detect the presence of the most common genetic abnormalities, the presence or absence of which has an impact on the patient's classification into the appropriate risk group. This work presents 3 BCP-ALL iAMP21-positive patients who were detected during routine genetic diagnostics using the FISH method and microarray test. iAMP21 is associated with a poor prognosis and high risk for relapse. Children with B-cell precursor lymphoblastic leukemia with this genetic entity are associated with a delayed treatment response. The FISH method and single-nucleotide polymorphism array provides a useful method to detect characteristic genetic changes.

Impact of early chimerism status on clinical outcome in children with acute lymphoblastic leukaemia after haematopoietic stem cell transplantation.

BACKGROUND: The significance of very early chimerism assessment before day + 28, which is considered the moment of engraftment, is still unclear. In this retrospective study, we evaluated the clinical impact of very early chimerism on the clinical outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukaemia (ALL). METHODS: The study group included 38 boys and 18 girls. Very early chimerism was evaluated on days + 7, + 14, + 21 and + 28 after the transplant. Short tandem repeat polymerase chain reaction (STR PCR) was used to analyse chimerism. RESULTS: Overall survival (OS) and event-free survival (EFS) were 84 and 80%, respectively. The OS in the group of 24 patients with complete donor chimerism on day + 14 was 83%, and it did not differ statistically compared to the 32 patients with mixed chimerism on day + 14 (OS was 84%). In our cohort of patients, the matched unrelated donor, male gender of donor, number of transplanted cells above 4.47 × 106 kg and no serotherapy with anti-thymocyte globulin (ATG) were statistically related to a higher level of donor chimerism. The immunophenotypes of disease, age of patient at time HSCT, recipient sex, stem cell source (peripheral blood/bone marrow) and conditioning regimen had no impact on early chimerism. Acute graft versus host disease grades II-IV was diagnosed in 23 patients who presented with donor chimerism levels above 60% on day 7. CONCLUSIONS: The data presented in this study provide valuable insight into the analysis of very early chimerism in children with ALL treated with HSCT.

Influence of Mixed Chimerism on Outcome in Children With Anaemia After Haematopoietic Stem Cell Transplantation.

BACKGROUND/AIM: In patients with non-malignant diseases, mixed chimerism is not a rare phenomenon. The clinical impacts of chimerism following allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with congenital anaemia (CA) and severe aplastic anaemia (SAA) were analysed. PATIENTS AND METHODS: We studied twenty-seven consecutive children with congenital and acquired anaemia who had undergone allogeneic haematopoietic stem cell transplantations. In the observed group of patients, the median of the follow-up was 6.12 years (2.00-14.8 years). RESULTS: Overall survival (OS) did not depend on the type of disease p=0.1. OS did not significantly differ in patients who received more than 5x106/kg stem cells (91%) and those who received less than 5x106/kg (85%) (p=0.61). Two patterns of stable mixed chimerism (SMC) were observed: SMC (95-97% cells of the donor), and SMC with a fluctuation between 50-90% of the cells of the donor. None of the surviving patients received immunosuppression treatments of chronic Graft-versus-Host Disease (cGvHD). CONCLUSION: Our results showed that mixed chimerism did not influence the survival of children with congenital and aplastic anaemia following allo-HSCT.