An aneuploid DNA stem line has been detected by flow cytometric measurements in 17 (29%) out of 59 children entered in the BFM 83 pilot study for ALL relapse. Of 17 DNA aneuploidies, 15 were hyperdiploid. Euploidy was observed in 28 of 34 patients with an early relapse, whereas 11 of 25 children suffering a late recurrence of disease showed aneuploid DNA stem lines. In contradistinction to ALL relapse, a significantly higher frequency (38%) of pretreatment DNA aneuploidy was measured in 376 newly diagnosed patients of the BFM trials. Our findings may reflect the impact of therapy on leukemic cell clones and their relapse pattern.

Aneuploidy↗

PubMed1987

[High dosage ARA-C in combination with mitoxantrone in therapy of acute myeloid leukemia in childhood. Initial results of the AML BFM-85 recurrence study].

19 children with AML were treated using the combination of high dose cytosine-arabinoside and mitoxantrone. All children were initially treated according to protocol AML-BFM-83. 6 children with refractory AML, 9 children with bone-marrow relapse during or after maintenance therapy and 4 children with residual blasts (5-25%) after remission induction and consolidation therapy AML-BFM 83 were treated with the relapse protocol. 6 of 15 children with refractory AML and all 4 children with residual blasts achieved a complete remission. 2 children died in bone-marrow aplasia and 1 child did not respond. One child died after further mitoxantrone treatment due to toxic cardiomyopathy. All children went into severe bone marrow aplasia, which lasted in median 27 days. These data indicate a high antileukemic activity of HD-ARA C/mitoxantrone in childhood AML.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

Frequency and clinical significance of DNA aneuploidy in acute leukemia.

Analyses of the cellular DNA content were carried out in 446 patients with newly diagnosed acute myeloid (AML) and lymphoblastic (ALL) leukemias in order to assess the frequency of DNA aneuploidies and its relation to immunologic and morphologic subtypes as well as its prognostic relevance. Based on high resolution FCM analyses and standardized reference measurements, DNA aneuploidies were identified at a similar frequency in children and adults with AML (38.0% and 40.0%) and ALL (40.0% and 37.4%). In AML aneuploid DNA stemlines were significantly less frequent in FAB-M 1 cases as compared to the other morphologic subtypes (p less than 0.05), whereas the degree of DNA aneuploidy was significantly lower in M 1 and M 2 leukemias as compared to the M 4 and M 5 subgroups (p less than 0.05). In ALL non-T/non-B and C-ALL revealed a higher frequency of DNA aneuploidies than T- and Null-ALL cases (p less than 0.05). No differences in the response to induction therapy were found between patients with and without DNA aneuploidy in children or adults with AML or ALL. In the childhood ALL trial BFM 79/81, however, a significantly higher frequency of long term remissions was observed in children with DNA aneuploidy (0.91 versus 0.66 at five years, p = 0.053). A similar though not significant tendency was also revealed from the AML studies BFM 78 in children and 78/81 in adults. In the subsequent studies these differences could not be confirmed at present, possibly because of the considerably shorter observation time.

Adult↗

PubMed1986

[Initial results of a study of the treatment of children with ALL recurrences].

Ninety-five children and adolescents with their first relapse of ALL were treated in the multicentric prospective trial ALL-REZ BFM 83. Treatment was stratified with respect to time and site of relapse. The overall remission rate was 86.3%. In the group of patients with early relapse only 44/56 children (78.6%) achieved a second remission, whereas the remission rate was 97.4% (38/39) in patients with late relapse. The 2 year probabilities of a sustained second complete remission are 0.65 +/- 0.10, 0.33 +/- 0.09 and 0.71 +/- 0.14 for patients with late, early and isolated CNS relapses, respectively. The poorest prognosis was observed in children with early marrow relapse (0.16 +/- 0.13 after one year).

Adolescent↗

PubMed1986

[Successful chemotherapy in a primary cerebral centroblastic non-Hodgkin's lymphoma in childhood].

Primary lymphomas of the central nervous system (CNS) are rare diseases. Often these tumors are surrounded by glia cells and may, therefore, be misdiagnosed as 'astrocytomas' with accompanying reactive lymphocytosis. A 15-year old patient was irradiated to the posterior cranial fossa and the brain stem because of a supposed astrocytoma. Five months after completion of radiotherapy he presented two lesions each in the right and left cerebral hemisphere. Repeated biopsy led to a revision of the primary diagnosis in favor of a B-cell Non-Hodgkin lymphoma (centroblastic type). After cyclic polychemotherapy including high-dose methotrexate and cytosine-arabinoside he entered a complete remission. No further radiotherapy was given. So far, 18 months after discontinuating therapy, the patient has been in complete remission and is in an excellent physical condition.

Adolescent↗

PubMed1985

Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.

One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event-free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.

Adolescent↗

PubMed1984

Acute lymphoblastic leukemia: current status of therapy in children.

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Age Factors↗

PubMed1984

Slight impairment of psychomotor skills in children after treatment of acute lymphoblastic leukemia.

Several studies have reported a decline in intelligence and cognitive functions in survivors of childhood acute lymphoblastic leukemia (ALL). Other investigators, however, have found no intellectual impairment in these children. Fifty-one long-term survivors of ALL, having been treated according to the protocols of the BFM Study Group from 1970 to 1979, were assessed retrospectively using neurophysical methods. The results were compared with those obtained from 30 patients with other malignancies, who had received neither radiation therapy to the central nervous system (CRT) nor any methotrexate during chemotherapy. Additionally, neurological examinations and cranial computed tomography (CCT) were performed. neuropsychological examinations included verbal functions, intelligence (performance), psychomotor speed, motor skills and sensory integration. The results of verbal tests and the IQs, tested by nonspeed-related measures, were within normal limits in both groups. About one-third of all patients showed mild disturbances of psychomotor speed and motor skills. Children with leukemia had lower scores than those with solid tumors for nearly all tasks, but only tests for sensory integration revealed significant differences between former ALL patients and tumor patients. Furthermore, the following results were obtained related to different therapeutic modalities: The higher total radiation doses had been during CRT (maximum 24 GY), the more neuropsychological functions were impaired, particularly motor accuracy and sensory integration. These disturbances improved with the length of survival. Widening of subarachnoidal space was found in 33% of the CCT obtained. There was no correlation between the intellectual functions of the survivors and the CCT abnormalities. Neurological findings mainly consisted of slight fine motor disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Achievement↗

PubMed1984

[Childhood B-cell lymphomas and leukemias. Improvement of prognosis by a therapy developed for B-neoplasms by the BFM study group].

In two consecutive therapy studies, the BFM multicenter study group treated 55 children with B-NHL from 1975 until 1981 and another 55 children with B-NHL and 22 with B-ALL since 1981. In the 1975/81 study, a therapeutic regimen which produced excellent results in non-B-NHL and -ALL, emerged to be much less effective in disseminated B-NHL. With this regimen the probability of continuous complete remission (CCR) in advanced disease was 34% only after 7 years. Since 1981, a new therapeutic regimen of higher specificity for B-neoplasias improved the probability of CCR at the present time to 100% in localised B-NHL, to 63% in disseminated B-NHL and even in B-ALL to 49%.

Adolescent↗

PubMed1983

Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.

Adult↗

PubMed1983

Cranial computed tomography of 64 children in continuous complete remission of leukemia I: relations to therapy in modalities.

64 children with acute lymphoblastic leukemia and non Hodgkin's lymphoma in continuous complete remission were studied by cranial computed tomography two months to 7 years after cessation of antileukemic treatment. 17 (27%) patients showed abnormal widening (grade 2) of external cerebrospinal fluid spaces, 20 (31%) minimal widening (grade 1). A significant correlation between grade 2 abnormalities and the duration of maintenance therapy and single cranial radiation dose was found, whereas the correlations with total radiation dose and with intensity of induction protocols were not significant. Widening of external cerebrospinal fluid spaces after cessation of therapy persisted.

Acute Disease↗

PubMed1983

Prognosis of acute lymphoblastic leukemia related to initial findings and treatment.

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Antineoplastic Agents↗

PubMed1982

Successful treatment of pulmonary and cerebral aspergillosis in an immunosuppressed child.

A favourable outcome was observed in a 12 year-old boy who developed invasive pulmonary and cerebral aspergillosis during antineoplastic treatment for central nervous system relapse of acute lymphoblastic leukemia. Combination therapy with amphotericin B and 5-Fluorocytosine led to complete regression of pulmonary infiltrates. Despite enlargement of the cerebral lesion monitored by computerized tomography, no viable fungi were found in the completely resected abscess after a 4 weeks' course of antifungal treatment preceding neurosurgery. Histological examination confirmed the diagnosis of an aspergillotic abscess. The initially severe neurological symptoms disappeared after successful surgery. Aspergillus fumigatus was detected in the soil of a potted ornamental plant in the mother's living room, suggesting that this might have been the source of the infectious agent.

Amphotericin B↗