Clinical characteristics and analysis of treatment result in children with Ph-positive acute lymphoblastic leukaemia in Poland between 2005 and 2017.

OBJECTIVE: The aim of this study was to analyse the clinical characteristics and outcome of children diagnosed with Ph+ ALL. MATERIAL AND METHODS: A total of 2591 newly diagnosed ALL children were treated in Poland between the years 2005 and 2017. Of those, 44 were diagnosed with Ph(+) ALL. The patients were treated according to protocols: ALL IC-BFM 2002 and 2009 (26 patients), EsPhALL (12 patients), initially ALL IC-BFM and then EsPhALL (6 patients). RESULTS: The median of follow-up in the observed group was 3 years. Overall survival (OS) and event-free survival (EFS) of Ph+ ALL group were 0.73 and 0.64. OS and EFS of patients after HSCT were 0.78 and 0.66, while without HSCT were 0.6 and 0.6, P = 0.27 and 0.63. OS was 0.8 for patients treated with chemotherapy plus imatinib and 0.61 for chemotherapy alone, P = 0.22, while EFS was 0.66 (imatinib therapy) and 0. 61 (without imatinib), P = 0.41. CONCLUSION: Our study suggests that adding imatinib to intensive chemotherapy seems to improve outcome. However, this study was limited by a small number of patients and a variety of chemotherapy regimens with or without imatinib.

Expression of chemokine receptors on peripheral blood T cells in children with chronic kidney disease.

Chemokine receptors play a role in leukocyte recruitment, activation, and maintaining effector functions and regulate adaptive immune response and angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptor combination in peripheral blood of children with chronic kidney disease (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+ lymphocytes was lower after HD session as compared to 15 min of session duration. During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3, and CXCR4 was constant. The alteration of chemokine receptors expression in children with CKD occurs early in the development. Diminished expression of CXCR3, CXCR4 on T cells in patients with CKD on HD might result in impaired inflammatory response. Increased CCR7+ T cell percentage could be responsible for the alteration of migration of cells into secondary lymphatic organs.

Chemokine receptors on peripheral blood T lymphocytes in children on peritoneal dialysis.

BACKGROUND: Immune cell dysfunction is listed among complications resulting from chronic kidney disease (CKD). It could be associated with T-cells, which play a role in the lymphocytic migration and infiltration. However, the data on chemokine receptors expression on T-cells in patients with CKD particularly treated with peritoneal dialysis (PD) are still limited. METHODS: The study aimed at multiparameter flow-cytometric analysis of the absolute numbers and percentage of T-cell subsets with surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptors' combinations in 47 children treated with PD. RESULTS: We found lower absolute numbers of total T lymphocytes, lymphocytes with surface CCR5, CXCR4+CCR5, CXCR3+CCR5 antigens and T-cells with CCR4, CCR4+CD4, CXCR3, CXCR3+CD4, and CD8 receptors. Lymphocytes T with CD4, CCR7, CD28+CCR7, CXCR3+CD8 antigens showed higher percentage in children on PD as compared to healthy children and opposite percentage values of CCR4+, CCR4+CD4+, CXCR3+ T lymphocytes were diminished. Mean fluorescent intensity for CCR7+, CCR7+CD45RO+, CCR7+CD28+, CXCR4+CD4+, CCR5+CD4+, CCR4+, CCR4+CD4+ T-cells was lower in the PD group than in healthy children. The analysis of correlation between T lymphocyte subpopulations with chemokine receptors and other parameters revealed positive correlation of CCR7+ and CCR7+CD28+ T-cells and weekly creatinine clearance, negative correlation between the percentage of CD45RO+CCR7 antigen positive T-cells and KT/Vurea. SUMMARY: In conclusion, we could not confirm the phenomenon of earlier senescence of T-cells in children with CKD on PD treatment. This still requires further investigation. The higher percentage of T-cells with CCR7 surface receptor could be responsible for the increase of proliferation activity in this group of children.

First-line treatment failure in childhood acute lymphoblastic leukemia: The polish pediatric leukemia and lymphoma study group experience.

The aim of this study was to evaluate the risk factors of relapse and treatment-related deaths in acute lymphoblastic leukemia (ALL) in children residing in Poland.A total of 1872 patients with newly diagnosed ALL, treated according to the ALL IC-BFM 2002 protocol in 14 Polish pediatric hematology centers from 2002 to 2012 were included in the study. Three-hundred eighty-four patients experienced treatment failure. The last follow-up was 31 December, 2016.Univariate analysis identified factors in each risk group that were significantly different between children whose treatment failed and those who remained in the first remission. Multivariate analysis demonstrated that only the age of 10 years or over at primary diagnosis in the high-risk group was an adverse prognostic factor. To facilitate the analysis, patients were divided into three groups: relapsed children who survived; relapsed children who died; children without relapse who died due to toxicity.Our analysis showed that age older than 10 years is a particular risk factor for the failure of first-line of treatment, both in terms of relapse and treatment-related mortality.

Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group.

The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: The risk factors, clinical features and non-hematological toxicity profiles during chemotherapy in acute lymphoblastic leukemia (ALL) patients treated in pediatric hematology centres were analysed. MATERIALS AND METHODS: A total of 902/1872 children were reported as having grade 3 or 4 toxicity. RESULTS: Among the analysed toxicities, infection and gastrointestinal and liver toxicities were the most common. The median follow-up was 6.8 years. Overall survival and event-free survival rates for the analysed group were lower than those reported for the group without grade ≥3 toxicity. In univariate analysis, we identified the number of toxic episodes, the risk group and remission status that had a significant impact on the outcome. Multivariate analysis demonstrated the risk group and the number of toxic episodes ≥3 to be statistically significant for the results. CONCLUSION: The toxic profiles investigated in our report should be used in future efforts to decrease the burden of side effects during chemotherapy.

[Comparative analysis of blast immunophenotype between the diagnosis and relapse of childhood acute lymphoblastic leukaemia - implications for monitoring of minimal residual disease]. / Analiza zmian immunofenotypu komorek bialaczkowych przy diagnozie oraz wznowie w dzieciecej ostrej bialaczce limfoblastycznej oraz ich wplywu na wykrywanie minimalnej choroby resztkowej.

PURPOSE: The aim of the present study was to compare the blast immunophenotype of acute lymphoblastic leukaemia (ALL) at diagnosis and at relapse and to define the most frequent shifts in marker expression. PATIENTS AND METHODS: Bone marrow samples from 14 patients were analyzed by flow cytometry both at diagnosis and at relapse - in 12 patients with B-cell precursor (BCP)-ALL and in 2 patients with T-ALL. RESULTS: The conversion in blast immunophenotype was observed in 12 out of 14 patients (86%). Antigen CD34 turned out to be the most unstable antigen - the shift in the signal expression was present in 57% of BCP-ALL and in both T-ALL cases. Regarding B-lineage markers, the shifts most frequently concerned CD20 (shifts present in 41.5% of cases) and CD22 (27%). Among the T-lineage markers: CD3, CD4 and CD8 demonstrated the highest incidence of altered signal expression. On the other hand, the most stable antigen included CD19 and CD10 for the BCP-ALL group and CD1a, CD2, CD5, CD7 for T-ALL patients. Expression of HLA-DR, TdT and CD45 antigens remained unchanged in both BCP-ALL and T-ALL groups. CONCLUSIONS: The results of the present study support the requirement to monitor at least two different leukaemia specific antigen combinations for detection of MRD to prevent a false-negative result and to increase the effectiveness of monitoring minimal residual disease.