Igor Olejnik

Assessment of Chosen Parameters of the Immune System in Children with Acute Lymphoblastic Leukemia

The immunosuppressive effect of cytostatics, basic therapeutic agents in the treatment of proliferative diseases of the hematopoietic system, and the rising number of children cured from acute leukaemias form together a need to monitor the status of the immune system following cessation of therapy. Surface antigens in lymphocytes from peripheral blood were assessed in 16 children directly after intensive chemotherapy (i.e., after protocol II of the BMF program) and in 25 children 12-13 months following conclusion of acute lymphoblastic leukemia treatment. The results were compared to data obtained from children never afflicted with neoplastic disease. A significant decrease in the average number of lymphocyte subpopulations was noted in the case of the treated children directly after intensive chemotherapy. The average values of lymphocyte subpopulations in children with concluded treatment are within the norm, with the exception of NK and TS lymphocytes.

Serum soluble L-selectin in childhood acute lymphoblastic leukemia

Abstract Background: Determination of the serum level of soluble (s)L‐selectin has been advocated for monitoring patient response to treatment in leukemia. The aim of the present study was to find out whether serum levels of sL‐selectin correlated with treatment for acute lymphoblastic leukemia (ALL) in children.

SIALIC ACID CONCENTRATION IN DIFFERENT STAGES OF MALIGNANT LYMPHOMA AND LEUKEMIA IN CHILDREN

Sialic acid concentration in the blood serum of 104 children suffering from leukemia and malignant lymphomas was determined. A significant higher concentration of sialic acid was found at the onset of the disease, compared to the controls. In the group of children suffering from acute lymphoblastic leukemia a dependence was noted between the stage of the disease and the concentration of sialic acid in the serum. The high concentration of sialic acid at the onset of the disease, although decreasing during treatment, rose again during relapses of the disease. It seems that determination of sialic acid concentration may be useful in monitoring treatment.

Individualized tumor response testing profile has a prognostic value in childhood acute leukemias: multicenter non-interventional long-term follow-up study

Abstract A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.

Acute lymphoblastic leukaemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation.

Objective. Production of cytokines that support T‐cell activation and proliferation and migration to lymph nodes is one of the most important terms of cancer vaccine development. In previous studies we and others used CD40 ligation to obtain higher expression of co‐stimulatory and adhesion molecules on leukaemic cells from children with acute lymphoblastic leukaemia (ALL). This time we assess the cytokine and chemokine gene expression profile in CD40‐stimulated ALL cells. Material and methods. Malignant cells from 25 children with BCP‐ALL were stimulated (or not) with huCD40LT and rIL‐4 for 96 h. Eleven different molecule, cytokine and chemokine mRNAs levels (CCR7, IL‐23, TGF‐β‐IP, IFN‐γ, IL‐10, CD1a, CD40, CD54, CD80, CD83, CD86) were determined using the real‐time PCR technique with TaqMan chemistry using ready‐to‐use low‐density arrays for gene expression by Applied Biosystems. Results. 1) Increases in mRNA levels for CD40, CD54 and CD80 after CD40L and IL‐4 stimulation were observed, 2) CCR7 mRNA expression was higher after CD40 ligation than before the culture (p = 0.002), 3) IL‐10 mRNA expression was higher after the culture with medium than before the culture (p = 0.01). Conclusions. The results show that leukaemia‐derived dendritic cells obtained with CD40 ligation express CCR7 – chemokine is involved in migration to lymph nodes and does not produce higher amounts of IL‐10, a potent immunosuppressive cytokine. Our preclinical findings could be used in the design of immunotherapy trials for the treatment of children with ALL.

Wzrost ekspresji mRNA dla MDC i TARC – chemokin biorących udział w migracji komórek dendrytycznych do węzłów chłonnych w komórkach ostrej białaczki limfoblastycznej po stymulacji CD40L – raport wstępny

Immunoterapia jest jednym z najnowszych kierunkow w leczeniu nowotworow. W ostrej bialaczce limfoblastycznej (ALL) u dzieci mozliwe jest przeksztalcenie komorek nowotworowych w komorki dendrytyczne prezentujące antygeny bialaczkowe limfocytom T gospodarza. W ten sposob, byc moze, bedzie mozna uzyskac eliminacje klonu bialaczkowego, tym samym wyleczenie pacjenta. Celem pracy byla ocena ekspresji genow dla wybranych chemokin w komorkach ALL po przeksztalceniu ich w komorki dendrytyczne. Material i metoda Do badania zakwalifikowano 25 dzieci leczonych w ośrodkach hematologii i onkologii dzieciecej w Polsce. Komorki ALL stymulowano za pomocą CD40L i IL-4. Ocene fenotypu komorek nowotworowych przed i po hodowli wykonano z uzyciem cytometrii przeplywowej (cząsteczki kostymulujące i adhezyjne), natomiast ekspresje genow chemokin na poziomie mRNA badano lancuchową reakcją polimerazową czasu rzeczywistego (real-time PCR). Wyniki 1. potwierdzono mozliwośc uzyskania fenotypu komorek dendrytycznych przez komorki ALL po stymulacji CD40L, 2. wykazano wzrost ekspresji chemokin MDC i TARC w komorkach ALL po przeksztalceniu do komorek dendrytycznych. Wniosek Wzrost wytwarzania chemokin MDC i TARC, biorących udzial w przyciąganiu limfocytow T do ognisk nowotworzenia, moze byc przydatny w konstruowaniu schematow immunoterapii u dzieci z bialaczkami.