Biomedical subjects

Danuta Sońta-Jakimczyk

Publications and source records attributed to Danuta Sońta-Jakimczyk.

28 records · Page 2Linked to original sources

PubMed2003

[Minimal residual disease in childhood acute lymphoblastic leukemia: diagnosis of the 21 century].

The detection of very low numbers of leukemic cells persisting after treatment, i.e. the monitoring of minimal residual disease (MRD) is of significant clinical value for children with acute lymphoblastic leukemia (ALL). Particularly, the assessment of early response to remission induction treatment has high prognostic value and enables more reliable definition of low-risk and high-risk patient groups. This forms the basis for treatment modification in new treatment protocols. The predictive value of MRD monitoring is particularly clear after first relapse. It enables recognition of low-risk patients with low MRD levels (probability of relapse-free survival (RFS) of 86%), whereas high MRD levels in high-risk patients are predictive of dismal outcome (probability of RFS of 0%). Moreover high MRD positivity before stem cell transplantation is strongly prognostic of relapse after transplantation.

Antineoplastic Agents↗

PubMed2003

[Leukemia in neonates and infants].

Leukemia diagnosed during the first year of life is a rare but highly malignant disease of hematopoietic system. In contrast to leukemias diagnosed after the first year of life, infant leukemia is characterized by distinct biological and genetic features, which influence the clinical course and disease outcome. Approximately 60% of acute leukemias in infants are associated with aberrations of chromosome 11q23 with the rearrangement of the MLL gene. Despite major progress in treatment of childhood leukemias, prognosis of infant leukemia (particularly in acute lymphoblastic leukemia--ALL) remains poor. The most unfavorable prognostic factors in infant ALL are age at diagnosis below 6 months, CD10 negativity, myeloid antigen co-expression, presence of MLL gene rearrangements and in particular poor response to steroids. Long-term event free survival (EFS) in infant ALL ranges from 20 to 40%, depending on treatment protocol. Slightly better results are achieved in infant acute myeloid leukemia.

Acute Disease↗

PubMed2003

[Advances in the treatment of children with high risk acute lymphoblastic leukemia (ALL) treated with modified "NEW YORK" protocols between 1987 and 2002].

From 1981 to 1986, in children with ALL and initial WBC > or = 50,000/mm3, over 6-year disease-free survival was significantly lower (33%) than in children with WBC < 50,000/mm3 (60%). In attempt to improve this unsatisfactory results, three modified American protocols named: "New York", "New York I", and "New York II", "New York I", and "New York II" were introduced consecutively in the centers of Polish Pediatric Leukemia Lymphoma Study Group (respectively, in 1987, 1997, and 1999). The treatment results achieved in three consecutive therapeutic groups of children with ALL and initial WBC > or = 50,000/mm3: group I--213 children (1987-1996), group II--58 children (1997-1999), and group III--52 children (1999-2001) are presented. The observation was completed in December 31, 2002. In three evaluated groups the first complete remissions (CRs) were achieved in 90.6%. 94.8%. and 94.2% of patients, respectively. Relapses occurred in 71 patients of group I (37%), in 9 patients of group II (16%), and in 6 patients of group III (12%). The complications of treatment caused death in 7 children of group I, in 1 child of group II, and in 2 children of group III. Eighty-one (38%), 11 (18.9%), and 9 (17.3%) patients, respectively, died due to progression of disease. The event-free survival (EFS) in three evaluated groups did not depend on age of children and WBC. The rates of 2-, 5-, and 10-year event-free survival (EFS) in group I were: 69.9%, 55.3%, and 53.6%, respectively and the rates of 2- and 5-year EFS in group II were: 80.7% and 72.7%, respectively. The rate of 2-year EFS in group III was 71.6%. The analysis of achieved treatment results in three evaluated groups shows the gradual improvement of the prognosis in children with ALL and initial WBC > or = 50,000/mm3 treated with the use of modified protocols "New York" and "New York I" in comparison with patients treated before 1987. Longer observation is needed for evaluation of efficacy and complications of "New York II" protocol.

Child↗

PubMed2003

[Efficacy of idarubicin in the treatment of childhood acute non-lymphoblastic leukemia: report of Polish Pediatric Leukemia/Lymphoma Study Group].

UNLABELLED: Results of treatment of childhood ANLL remained unsatisfactory for a long time, and introduction of a new drug seemed justified as the EFS achieved in this disease between 1993-97 was 42%. In 1998 a new protocol containing idarubicine in dose 12 mg/m2 (each dose regardless of treatment phase) was introduced. Between 1998 and 2001, 137 children with ANLL were referred to nine participating centers of PPLLSG. Thirty nine were uneligible, so 98 were evaluated. Among them 56 were qualified to standard risk group (SRG) and 35 to high risk group (HRG). In 7 children the risk group was not established due to early death. Remission rate was 79% in the whole group and 98% and 63% in SRG and HRG, respectively. The actuarial 3-year overall survival (OS), 3-year event-free survival (EFS) and 3-year event-free interval (EFI) are respectively: In the whole group 61%, 54% and 67%; in SRG 81%, 70% and 71%; in HRG 40%, 40%, and 53%. CONCLUSIONS: Due to introduction if idarubicine significant improvement of the results was achieved in SRG (better OS, EFS and EFI). Better new treatment methods are required in HRG.

Adolescent↗

PubMed2003

[Tumor lysis syndrome in the course of acute lymphoblastic leukemia as the consequence of prednisone monotherapy].

Authors present the case of 15-year-old girl with diagnosed pre T-acute lymphoblastic leukaemia with hyperleukocytosis--at admission 213 x 10(9)/l. At clinical evaluation a major peripheral and abdominal lymphadenopathy, mediastinal mass, hepatosplenomegaly were revealed. After administration of prednisone for two times--11.4 mg/m2/24 h--the features of tumour lysis syndrome rapidly increased. Hyperphosphatemia, hyperkalemia and hyperuricemia resulted in acute renal failure. Renal replacement therapy was introduced with simultaneous application of cytoreduction phase therapy and induction of remission according to New York protocol. Total number of performed hemodialysis sessions was 12. Obtained haematological remission in 8th week of treatment is still present. Renal function remains normal. Remission supportive treatment has been continued according to above-mentioned protocol.

Adolescent↗

PubMed2002

In vitro activity of oxazaphosphorines in childhood acute leukemia: preliminary report.

Glufosfamide (beta-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n = 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 microM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.

Adolescent↗

PubMed2002

Cross-resistance to five glucocorticoids in childhood acute lymphoblastic and non-lymphoblastic leukemia samples tested by the MTT assay: preliminary report.

In vitro antileukemic activity of five glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and non-lymphoblastic leukemia were determined by means of the MTT assay in 25 leukemia cell samples of childhood acute leukemias. The equivalent antileukemic concentrations of the drugs tested were: 34 microM hydrocortisone (HC), 8 microM prednisolone (PRE), 1.5 microM methylprednisolone (MPR), 0.44 microM dexamethasone (DX) and 0.22 microM betamethasone (BET). In comparison with initial ALL cell samples, the relapsed ALL group was more resistant to PRE (38-fold, p = 0.044), DX (> 34-fold, p = 0.04), MPR (38-fold), BET (45-fold) and HC (33-fold). The AML cell samples were even more resistant to: PRE (> 85-fold, p = 0.001), DX (> 34-fold, p = 0.004), MPR (> 69-fold, p = 0.036), BET (> 69-fold, p = 0.038) and HC (54-fold, p = 0.059) when compared with ALL on initial diagnosis. A significant cross-resistance among all the glucocorticoids used was found. Only in some individual cases the cross-resistance was less pronounced.

Adolescent↗

PubMed2002

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.

Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

[Echocardiographic assessment of circulation system in patients during and 3-5 years after all therapy in childhood].

Circulatory disturbances may occur during and after the treatment of acute lymphoblastic leukemia (ALL). The reasons are: leukemic infiltrations of the heart, anaemia, renal disturbances, infections, cardiotoxic drugs, especially anthracyclines (Atc). The aim of the study was echocardiographic assessment of circulatory system in patients during and 3-5 years after ALL therapy in childhood. The study group (group B) consisted of 20 children, aged 1-16 years, who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and cardioprotective agent--dexrazoxane. In this group echocardiography was performed before the treatment as well as after 1, 6, 12 months and 3 years. The retrospective group (R) consisted of 36 persons aged 12-24 years, examined 3-5 years after the completion of ALL treatment, who had undergone the treatment with Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K) consisted of 28 healthy volunteers, aged 9-25 years. In all subjects echocardiography was performed, standard measurements taken, systolic and diastolic indices of left ventricle (LV) function calculated. In patients during and 3-5 years after the treatment neither LV dilatation nor abnormal wall-thickness was found. The systolic indices remained normal. In the group B echocardiographic indices did not change significantly during 3 years of treatment and did not correlate with growing cumulative Atc doses. In this group isovolumetric relaxation time (IVRT) was significantly longer, what emphasized the need of further clinical and echocardiographic follow-up.

Adolescent↗

PubMed2002

[T lymphocyte alpha/beta and gamma/delta in peripheral blood of children with acute lymphoblastic leukemia].

The improvement in acute lymphoblastic leukemia (ALL) children treatment results in the need of examining their immune system after therapy. The purpose of the research was the immune system evaluation in children with low risk ALL diagnosis, during the treatment and twelve months after therapy. The examined material included 41 children. A group of 16 patients was examined during the above the treatment, immediately after intensive chemotherapy. The other 25 patients were examined twelve months after the completion of therapy. The lymphocyte immune phenotype was examined with FACScan flow cytometer using monoclonal antibodies. The study confirmed the intensive chemotherapy significantly decreases the number of leukocytes, lymphocytes and their subpopulations. The period of 12 months after cessation of the chemotherapy is sufficient to recover the immune system function in all examined low risk ALL children.

Child↗