Late-onset idiopathic thrombocytopenic purpura correlates with rapid B-cell recovery after allogeneic T-cell-depleted peripheral blood progenitor cell transplantation in children.
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Biomedical subjects
Publications and source records attributed to J Boguslawska-Jaworska.
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OBJECTIVE: The purpose of the present work was estimation of liver function using the phenazone test and commonly used biochemical tests in children with acute lymphoblastic leukemia (ALL) during anticancer treatment. METHODS: Observations were carried out in the same 21 patients with ALL before the beginning of chemotherapy, after Protocol I and after Protocol M of the antileukemic treatment carried out according to the program BFM 86. RESULTS: The applied chemotherapy inhibited phenazone elimination. Both phenazone half-life and metabolic clearance rate were significantly different in patients after treatment with anticancer drugs, especially with high-dose of methotrexate (MTX), from those in patients before the beginning of chemotherapy (p < 0.001). Moreover, after MTX administration transaminases activity and serum bilirubin concentration were significantly higher than before treatment (p < 0.05). CONCLUSION: Our results showed that in children with acute lymphoblastic leukemia, anticancer chemotherapy decreased liver metabolic capacity. Particularly, high-dose methotrexate treatment altered the elimination of phenazone by inhibiting the activity of hepatic mixed function oxidase system. This change may lead to an increase in toxicity of active drugs which are metabolized by this enzyme system. In addition, altered activity of liver metabolic function can impair transformation of prodrugs to active forms. It should be considered in selection of individual drug dosages. The objective estimation of the type and degree of liver dysfunction can only be achieved by the combination of a quantitative phenazone dynamic test and static biochemical tests.
The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed.
Intensive chemotherapy programme in children with cancer may result in psychological mal adjustment. Treatment facilities as well as psychological support are of great importance to minimize these side effects. In 1998 the programme of psychological support was introduced in 7 Polish paediatric haematology / oncology centres. Psychological adjustment of patients treated in each centre was examined 5 yrs after the termination of therapy. At the same time children with new diagnosis of cancer were monitored psychologically along with the psychological support programme. Psychological status of each patient was examined with the following tests: Cattell's questionnaires (CPQ, HSPQ), Manifest Anxiety Scale, Spielberger's inventories (STAI, STAIC), Wechsler Intelligence Scale. The programme of psychological support was based on guidelines of SIOP Psychosocial Committee and included such elements as informing about diagnosis and treatment, explaining any doubt, maintaining an open communication, educational care in the periods of treatment, encouraging to activity even during periods of discomfort. The analysis showed that most of the participating centres could only provide some elements of the support programme. The main problem was to convince medical staff to inform children on diagnosis and treatment plans. Preliminary results of the study indicate that full psychological support for children with cancer and their families from the beginning of therapy can result in improvement in psychological adjustment. During the ensuing period, patients and their parents appreciate the possibilities to contact a psychologist.
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A total of 527 children with acute lymphoblastic leukaemia (ALL) from the most frequent risk groups: standard risk group (SRG) and intermediate risk group (IRG) were treated between 1987 and 1991 according to an intensified treatment program (based on the BFM protocol) including the use of an intermediate dose of methotrexate in the IRG. A comparison of the treatment results in this group from 513 children treated between 1981 and 1987 indicates that the chance for a 6 year event-free survival has increased to 73% (previously 55%).
The subject of analysis is a group of 111 children with acute lymphoid leukemia (ALL) whose remission has lasted at least 4 years since stopping treatment. Patients were observed from 4 to 18 years after ALL therapy. No symptoms of disease were observed in 110 children; one child had leukemic infiltration of the testes during the fifth year after stopping treatment. In this group of children no changes in physical development have been recorded, but a growth deficiency is sometimes noted. No symptoms of intrinsic organ lesions have been ascertained in most of the patients. All of the patients, except one with schizophrenia, lead normal lives and either attend school or go to work. Seven patients have healthy children, who were born 6-24 years after the beginning of the disease and 3-16 years after cessation of therapy.
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A 12-year-old boy with myelodysplastic syndrome underwent a double transplantation of hematopoietic progenitor cells from his haploidentical brother. After conditioning with busulfan, cyclophosphamide, and Vepesid, the first bone marrow transplantation was performed using 3.53 x 10(6)/kg of CD34+ cells. Initial engraftment was followed by graft rejection. The second conditioning consisted of melphalan and anti-thymocyte globulin. The boy was then transplanted with 5.15 x 10(6)/kg of CD34+ cells, harvested from bone marrow (BM) and peripheral blood. Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine A + short methotrexate. Hematological recovery was rapid and stable. Acute GvHD 1 degree (skin) resolved after 2 weeks of steroid treatment. A relapse occurred on day +140. At that time NK cells decreased from 20 to 7% with the lowest CD4+/CD8+ ratio, 0.07. Just after relapse, the percentage of cytokine-induced killer cells (CIK-CD3+CD56+) dropped from 3.34 to 0.1%. CsA treatment was stopped and the patient received T cell (CD3+ cells) add-back four times on days +146, +199, +234, and +262 in doses of 0.5 x 10(5), 1.0 x 10(5), 2.0 x 10(5), and 4.0 x 10(5)/kg, respectively. No acute GvHD occurred. Additionally, bone marrow biopsy before the second add-back showed complete remission. Analysis of lymphocyte subsets before the fourth add-back showed the highest values of CD4+, NK, and CIK cells and also the highest CD4+/CD8+ ratio.