Biomedical subjects

J Harbott

Publications and source records attributed to J Harbott.

113 records · Page 7Linked to original sources

PubMedDate not supplied

[Detection of aberrations in the karyotype of children with acute leukemia: a comparative analysis of cytogenetics and flow cytophotometry].

In the present study a comparative analysis of DNA flow cytometry and cytogenetics was performed in 257 children with acute leukemias to evaluate the comparability of both techniques for the detection of karyotype aberrations. DNA aneuploidies were detected in 88 (34%) patients while cytogenetic anomalies were revealed in 96 (37%) cases. From 76 patients (30%) with cytogenetically inevaluable metaphases 26 (35%) expressed aneuploid DNA stemlines. 67 (79%) of the 85 patients with normal karyotypes or normal modal chromosome numbers had a DNA index of 1.0 while DNA aneuploidies were identified in 18 cases (21%). 4 of 30 patients (13%) with pseudodiploid karyotypes revealed aneuploid DNA stemlines. While aberrations of the chromosome number by 1-3 chromosomes were combined with DNA aneuploidies in 9 of 35 cases (26%) only, all 31 patients with higher numeric chromosome changes also had aneuploid DNA stemlines. These data indicate that cytogenetics and DNA flow cytometry are complimentary methods for the detection of karyotype aberrations and should therefore be applied simultaneously.

Child↗

PubMedDate not supplied

[Biclonal leukemia O-ALL/AMoL) with 11;19 translocation and trisomy X in an 8-month-old girl].

Biclonal leukemia was diagnosed in an 8 months old girl, combining lymphoblastic (FAB L1) and monoblastic (FAB M 5) phenotypes which were classified as O-ALL and AMol by immunological examination of surface-antigens. Chemotherapy for one cell type resulted in predominance or relapse of the other one. Chromosomal abnormalities diagnosed in the lymphoblastic clone consisted of translocation t(11;19)(q23;p13) and triple X. The breakpoint 11q23 neighbouring one well known oncogene (ets) is not strictly associated with special leukemic phenotypes. But it is often found in infants and usually correlated with a poor prognosis. The data of 18 patients with hybrid leukemias registered in the BFM studies strongly support the fatal course of the disease. 12 months after diagnosis approximately 1 out of 10 children is expected to survive disease-free.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group.

Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.

Adolescent↗

PubMedDate not supplied

[Acute myeloid leukemia in children with Down syndrome].

Forty-four children, aged between 0.4 and 16.2 years (median 2.0 years) with Down's syndrome and acute myelogenous leukemia (AML) including subacute megakaryoblastic leukemia (M7) were diagnosed between 1980 and 1986 (group 1, n = 16) or between 1987 and 1992 (group 2, n = 28). The leukemic blasts from Down's syndrome patients often proved difficult to classify. In group 1 the most frequent diagnoses were FAB M5 (6 pts.), M6 (3 pts.), in 3 patients the morphological diagnosis of M7 can retrospectively be assumed. In group 2, 15 of 28 patients were classified as M7, in 3 patients based on morphology alone, and in the other 12 patients confirmed by immunophenotyping or biopsy. The other children in group 2 were classified as: FAB M0 (3 pts.), M1 (1 pt.), M4 (2 pts.), M5 (2 pts.), M6 (4 pts.), M6/M7 (1 pt.). Initially, the latter and 10 of the patients with M7 presented with < 30% of blasts in the bone marrow. Karyotyping in 12 of 13 children frequently revealed numeric abnormalities, particularly trisomies involving chromosomes 8 (n = 6), 11 (n = 3), 21 (n = 3) and 14 (n = 1) in addition to the constitutional + 21c. Six patients in group 1 received no specific treatment, while 10 children were treated according to the protocols AML-BFM-78 or -83. Four of them are still alive for more than 5 years, two others died from infections in remission after 1.0 and 3.8 years. Fourteen of the 28 patients in group 2 did not receive any chemotherapy (10 with M7), and subsequently died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

[Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents: the significance of initial therapy response in blood and bone marrow].

In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗