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At least 1,207 records · Page 67Linked to original sources
PubMed1996

P300 abnormalities in long-time survivors of acute lymphoblastic leukemia in childhood--side effects of CNS prophylaxis?

The incidence and the degree of P300 abnormalities in relation to psychometric findings was assessed in two groups of long-term survivors of acute lymphoblastic leukemia (ALL) in childhood. The study was performed as part of a follow-up trial, evaluating CNS late-effects after antileukemic therapy, 7.1 +/- 1.6 years after cessation of antileukemic therapy. Subject groups differed primarily in terms of antileukemic CNS prophylaxis: combined radio- and chemotherapy (n = 8) vs. chemotherapy alone (n = 5). Results were compared with those of a third group of healthy controls (n = 13) matched for age and gender. P300 recordings were obtained during a visual oddball-paradigm using checkerboard reversal stimuli of different pattern sizes as target and background events. Neurophysiological data were correlated with the results of a psychological test battery, which measured general intelligence, non-verbal visual memory functioning and concentration. ERP analysis showed a significant prolongation of the P300 latency in irradiated subjects when compared to healthy controls and non-irradiated long-term survivors. Topographical data comparisons revealed substantial P300 differences in both ALL long-term survivor groups when compared with healthy controls. This demonstrated significantly lower amplitudes over the left frontal derivations, associated with lowered concentration abilities, in the irradiated subject group. Higher amplitudes over the parieto-temporal derivations of the right hemisphere, associated with significantly impaired visual memory capabilities, were seen in both long-term survivor groups.

Adolescent↗
PubMedDate not supplied

Prevention of CNS recurrence in childhood ALL: results with reduced radiotherapy combined with CNS-directed chemotherapy in four consecutive ALL-BFM trials.

BACKGROUND: The introduction of cranial radiotherapy (CRT) has provided efficient control of overt or subclinical meningeosis in acute lymphoblastic leukemia (ALL). Especially due to the long-term toxicity of CRT, reduction or elimination of radiotherapy appeared mandatory after cure rates of more than 70% had been achieved in ALL. The Berlin-Frankfurt-Münster (BFM) Study Group initiated several attempts in certain ALL subgroups to omit or reduce CRT while using more CNS-directed chemotherapy but without extended intrathecal treatment during maintenance therapy. This analysis summarizes the essential results that are in particular relevant because irradiation of the central nervous system (CNS) has been further reduced in the most recent trial ALL-BFM 95. PATIENTS AND METHODS: More than 4000 patients enrolled between 1981 and 1995 in one of the last four ALL-BFM trials have been analyzed to demonstrate the efficiency of intensive systemic and intrathecal chemotherapy with or without reduced CRT in the prevention of CNS relapses. RESULTS: In trial ALL-BFM81, it was shown that only in low-risk (LR) patients preventive radiotherapy can be replaced safely by intermediate dose (0.5 g/m2) methotrexate (MHD-MTX). In intermediate risk (IR) patients this attempt failed: IR pts had 8 times more CNS relapses if treated by MHD-MTX without CRT. In the subsequent trial ALL-BFM 83, all pts received MHD-MTX. IR pts were randomly treated with 12 or 18 Gy of preventive CRT which did not result in a significantly different outcome. The results from the subsequent trial ALL-BFM 86, using a more intensive consolidation with high-dose methotrexate (HD-MTX), demonstrated that the elimination of CRT in low-risk ALL, the reduced CRT of 12 Gy for IR, 18 Gy for medium (MR), and the reduced CRT with 18 Gy for high risk (HR) ALL, respectively, was justified: the incidence of relapses with CNS involvement was reduced to less than 5% (Reiter et al. 1994, Blood 84: 3122). When even less intensive preventive CRT (12 Gy for all medium and high risk patients) was used in trial ALL-BFM 90, the rate of CNS-related relapses was again below 5%. HR patients now treated with more CNS-directed chemotherapy had the lowest rate of CNS-related relapses observed so far in the BFM trials, even though CRT was also reduced to 12 Gy. Patients with T-cell ALL were shown to be protected from CNS recurrence by the combination of CRT (12 Gy) and HD-MTX more effectively than by HD-MTX in consolidation and TIT therapy during maintenance, especially if they presented with high WBC as shown in a joint AIEOP/BFM analysis (Conter et al. 1997, JCO 15: 2786). Patients with overt meningeosis which are characterized by a high leukemic cell load at diagnosis had a rate of recurrences that was comparable to that of patients with high WBC but no CNS disease. CONCLUSION: Low-risk ALL patients can be efficiently prevented from CNS relapse by intensive systemic and intrathecal chemotherapy without CRT. Patients with intermediate or medium risk ALL, including T-cell ALL, did not suffer from more CNS or systemic relapses when CRT was reduced to only 12 Gy. Patients with inadequate response to therapy are at particularly high risk for relapse with CNS involvement. Therefore, more CNS-directed systemic and intrathecal chemotherapy was applied in trial ALL-BFM 90, combined with only 12 Gy cranial irradiation, and improved the control of CNS recurrence. It seems likely that larger subsets of B-precursor ALL can be protected from CNS-related relapse by intensive chemotherapy without extended IT treatment and without CRT. This is being investigated in the ongoing trial ALL-BFM 95.

Adolescent↗
PubMedDate not supplied

[Late sequelae of CNS recurrence of acute lymphoblastic leukemia in childhood].

Study objective was to evaluate retrospectively central nervous system (CNS) morbidity of children with acute lymphoblastic leukemia treated with intensive chemotherapy and cranial radiotherapy for a first isolated or combined CNS relapse. Neurological (Touwen), neuropsychological (CFT 20, Wechsler scales, d2 attention test) and neuromorphological (CT, MRI) assessments were performed in 17 children (9 girls, 8 boys) aged between 7 and 14 years. Patients were off therapy for median 4 years; cranial radiotherapy for CNS relapse (12-24 Gy) was given to all patients 2 to 9 years ago (median 5.5 years). Ten patients had received preventive cranial radiotherapy during front-line treatment, previously. In this group, the cumulative radiation dose ranged between 30 and 39 Gy. Patients received 12 to 30 intrathecal methotrexate doses (median 22). Compared with normative levels for age (100 points) performance IQ (89.9) and full scale IQ (92.0), Culture Fair IQ (88.3) and attention and concentration (90.9) were significantly impaired. Verbal IQ (95.5) was not significantly different from normal expectations. Neurological investigations of 16 patients showed mild signs in 7 (44%) of them, mostly of fine-motor skills and coordination, but no major motor disability. In MRI and CT, white matter changes or ventricular enlargement were noted in 10 of 16 patients (63%). Parent-completed questionnaires indicated problem behaviors in 5 children. Cumulative doses of methotrexate correlated significantly with neuropsychological test results. Children irradiated twice as well as girls had poorer cognitive functions, not being statistically significant. Despite pathological test results, all children attended a normal school and did not exhibit obvious impairment in daily life. In conclusion, CNS relapse and attendant therapy, mostly consisting of a second course of cranial radiotherapy, caused measurable intellectual deficits and CNS morbidity, which did not result in severely impaired performance. Periodic psychological und clinical examinations are recommended for recognition of delayed morbiditiy and early intervention.

Adolescent↗
PubMed1992

Elective testicular biopsy at the end of maintenance treatment for acute lymphoblastic leukemia. A prospective study.

Open testicular wedge biopsy has electively been performed prior to completion of maintenance therapy for acute lymphoblastic leukemia. 25 boys during 6 years were included in this prospective study. Three boys developed testicular enlargement while on maintenance therapy and biopsies confirmed testicular leukemia. The remaining 22 boys were biopsied at termination of maintenance therapy. Occult testicular relapse was revealed on histologic examination in only one boy with normal testicular size. During the follow-up period, one boy developed overt testicular relapse two months after negative biopsy. These results will not justify electively performed routine biopsy prior to termination of chemotherapy. Instead, careful and minute clinical examination of the testicles, estimating their size and consistence, should be performed regularly at short intervals.

Adolescent↗
PubMed1987

[Risk-adapted treatment of immunocytomas].

For 176 patients seen between 1976 and 1984, with a mean age of 65 years, the probability of survival after ten years was 56% for lymphoplasmocytoid (n = 86), lymphoplasmocytic (n = 38) and non-classifiable (n = 10) subtypes, while it was 0% at the end of 6.5 years for the polymorph cell type (n = 42). Patients up to 60 years of age had, at 68%, a generally better prognosis than older ones, at only 30%. Cases with bone-marrow infiltration or leukemic washout (n = 114) were, like chronic lymphoid leukemia cases, classified according to the scheme of Rai and co-workers, while the remaining cases (n = 62) were classified according to the Ann Arbor scheme. There was a three-step prognosis of ten-year probability of 85% for stages I A, Rai 0, Rai I (n = 49), 50% for II A/B, III A, Rai II (n = 43), and 27% for III B/IV B and Rai III/IV (n = 41) of the non-polymorph cell subtypes. For the polymorph cell forms there was also a triple division with 88%, 53% and 14% after only four years. Additional unfavorable factors were rapid lymphoma growth, leukemic course, high paraprotein gradient and autoimmune hemolysis. The flexible employment of polychemotherapy and large-field radiotherapy, adapted to the mentioned unfavorable risk factors and age, contributed to the improved results in this heterogeneous group.

Adult↗
PubMed1992

In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides.

The c-myb protooncogene encodes proteins that are critical for hematopoietic cell proliferation and development. Disrupting c-myb function might, therefore, prove an effective therapeutic strategy for controlling leukemic cell growth. Antisense oligodeoxynucleotides have been utilized for this purpose in vitro, but their in vivo efficacy has not been reported. We therefore established human leukemia-scid mouse chimeras with K562 cells and treated diseased animals with phosphorothioate-modified antisense oligodeoxynucleotides. K562 cells express the c-myb protooncogene, which served as the target for the antisense DNA. They also express the tumor-specific bcr-abl oncogene that was utilized to track the human cells in the mouse host. Once circulating leukemic blast cells had been detected, the survival of untreated control mice was 6 +/- 3 days (mean +/- SD). The survival of animals treated for 7 or 14 days with either sense or scrambled-sequence c-myb oligodeoxynucleotides was not statistically different from the control animals. In distinct contrast, animals treated for similar lengths of time with antisense c-myb oligodeoxynucleotides survived at least 3.5 times longer than the various control animals. In addition, animals receiving antisense c-myb DNA had significantly less disease at the two sites most frequently manifesting leukemic cell infiltration, the central nervous system and the ovary. These results suggest that phosphorothioate-modified antisense DNA may be efficacious for the treatment of human leukemia in vivo, and by analogy, for the treatment of other human neoplasias.

Animals↗
PubMed1999

The characterization of human brain tumor using magnetization transfer technique in magnetic resonance imaging.

The clinical applicability of magnetization transfer (MT) technique in magnetic resonance imaging (MRI) for the estimation of the histological and constitutional feature of brain tumors was investigated. MT effect was evaluated by measuring the MT ratio (MTR). The parameters in 1.5-tesla MRI system were as follows: TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency of off-resonance MT pulse, 1000 Hz. The sequence was performed in 20 normal volunteers and 45 patients with brain tumors which were characterized histologically and surgically. The MTR for brain tumors was significantly lower than that for normal brain tissue (p < 0.05). The MTR for meningioma was higher than that for the other brain tumors (p < 0.05). In the meningiomas, MTR for fibrous type was higher than that for meningothelial type, but there was no statistical significance. Regarding the physical consistency for the brain tumors, as classified by surgery, there was a statistically significant difference in MTR between the soft tumor group (0.22 +/- 0.03, n = 6) and the hard tumor group (0.36 +/- 0.04, n = 10) (p < 0.01). This study suggested that the MT technique for patients with brain tumor may be useful to understand the characteristics of the tumors presurgically, based on the degree of intermolecular interaction of macromolecule such as protein.

Adenoma↗
PubMedDate not supplied

New agents for intrathecal administration.

Intrathecal administration of chemotherapy, with or without radiation therapy, is the primary treatment modality for the prevention and treatment of central nervous system (CNS) metastases in patients with leukemia or lymphoma. Although this treatment strategy has been very effective for patients with hematological malignancies, currently available intrathecal agents are relatively ineffective for patients with neoplastic meningitis resulting from an underlying solid or CNS tumor effective. This article provides an overview of some of the practical considerations and limitations associated with intrathecal chemotherapy, and is followed by a comprehensive review of some of the preclinical and early phase clinical trials of novel anticancer agents and treatment strategies using the intrathecal route.

Animals↗