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Biomedical subjects

G Schellong

Publications and source records attributed to G Schellong.

At least 37 records · Page 2Linked to original sources
PubMed1992

Treatment results of three consecutive German childhood AML trials: BFM-78, -83, and -87. AML-BFM-Group.

Acute myelogenous leukemia (AML) represents a heterogenous group of leukemias in adults as well as in children. The BFM group initiated 3 consecutive studies on the treatment of this disease. Between December 1978 and April 1991, 543 children under the age of 17 years entered the 3 consecutive multicenter studies, AML-BFM-78 (n = 151), AML-BFM-83 (n = 182), and the still ongoing study AML-BFM-87 (n = 210). The treatment strategy of BFM-78 consisted of an eight week induction/-consolidation regimen employing 7 different drugs together with cranial irradiation, followed by continuous maintenance for two years. The main alteration in the second study BFM-83 was the addition of an intensive 8-day ADE induction course (cytosine arabinoside, daunorubicin, etoposide). In the ongoing trial BFM-87 two courses of HD-ARA-C and etoposide are given after consolidation. CR rates were 80% in trials I and II, and 78% in trial III. The probability of a 4.5-year event-free survival was 35%, SD 4% in study I; 49%, SD 4% in study II, and 45%, SD 4% in study III. The probability of a 4.5-year event-free interval (EFI) was increased from 45%, SD 5% in study I to 61%, SD 4% in study II, it is in the same range in study III (58%, SD 5%). Seven of 10 children which underwent bone marrow transplantation (BMT) in 1. CR are still in first CR after a maximum follow-up time of 3.5 yrs. In summary, the addition of HD-ARA-C together with etoposide given after induction/consolidation treatment did not further reduce the incidence of relapses in childhood AML. So far, the results of study BFM-87 are in the same range than those of study BFM-83.

Adolescent↗
PubMed1991

Urinary excretion of the enantiomers of ifosfamide and its inactive metabolites in children.

The precondition for the antineoplastic effect of ifosfamide (ifo) is the oxidation of the oxazaphosphorine ring system, which contains a chiral centre at the phosphorous atom. This "ring oxidation" leads to the formation of alkylating mustard via several steps. A second metabolic pathway produces the cytostatically inactive metabolites 2- and 3-dechloroethyl-ifosfamide (2-d- and 3-d-ifo). The urinary excretion of the optical isomers of unmetabolised ifo and of 2- and 3-d-ifo, which represents the amount of ifo that has not been activated, was investigated by capillary gas chromatography for 18 treatment cycles in 14 children on various therapeutic schedules. The total cumulative excretion in 12 completely sampled cycles ranged from 27% to 50% of the ifo dose. Between 14% and 34% of the dose could be detected as ifo; 9% to 29%, as 3-d-ifo; and 2% to 8%, as 2-d-ifo. At 24 h after the end of therapy, excretion was nearly complete. Without exception, slightly more R-ifo (53%-61%) than S-ifo was excreted. S-2-d-ifo (50%-73%) was the main 2-d-metabolite. S-3-d-ifo (deriving from R-ifo) predominated in 6 of 14 children and R-3-d-ifo, in 8. Enantiomer-specific excretion increased after the end of infusion (up to 73% for R-ifo and 27% for S-ifo). We demonstrated stereospecific metabolism of ifo in children, with two different patterns of side-chain oxidation being observed. There was no evidence of important stereospecific ring oxidation in most children. A benefit should not be expected from the therapeutic application of pure enantiomers.

Adolescent↗
PubMed1990

Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group.

The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM-83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group.

Adolescent↗
PubMed1990

The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence.

Testicular function was evaluated in 75 boys after treatment for Hodgkin's disease with involved-field or extended-field irradiation and stage-dependent chemotherapy (vincristine, prednisone, procarbazine, Adriamycin [doxorubicin], and cyclophosphamide [OPPA/COPP]). Although pubertal development and testosterone levels were normal in all patients, 18 of 75 (24.0%) had elevated basal and 65/74 (87.8%) elevated stimulated luteinizing hormone (LH) levels, demonstrating chemotherapy-induced Leydig cell damage. In addition, there was a 40.5% and 53.4% incidence of elevated basal and stimulated FSH values, respectively, indicating severe impairment of spermatogenesis as confirmed by azoospermia in four patients. Testicular dysfunction was observed in patients treated before as well as during puberty. The incidence of elevated basal follicle stimulating hormone (FSH) and LH values was significantly higher in patients who had received higher cumulative doses of chemotherapy, i.e., 28.9% and 13.2% with two OPPA, 45.5% and 36.4% with two OPPA/two COPP, and 62.5% and 43.8% with two OPPA/four to six COPP, respectively. Chemotherapy for Hodgkin's disease causes a high and apparently dose-related incidence of testicular dysfunction in prepubertal as well as in pubertal boys affecting Leydig cell function as well as spermatogenesis. Circumstantial evidence indicates that procarbazine is the major gonadotoxic agent involved.

Adolescent↗
PubMed1990

Central nervous system relapse prevention in 1165 standard-risk children with acute lymphoblastic leukemia in five BFM trials.

In treatment of childhood ALL, prevention of CNS relapse by cranial irradiation is followed by considerable long-term sequelae. In the three ALL-BFM (Berlin-Frankfurt-Münster) trials 70, 76, and 79, employing radiotherapy (8.5 Gy craniospinal, 18 or 24 Gy cranial irradiation) in all arms, the incidence of CNS relapses (isolated and combined) in standard-risk patients (SR, 60% of all children) was consistently less than 6%. A risk factor (RF) calculated from absolute blast number, liver, and spleen size at diagnosis was used to stratify patients in the subsequent trials ALL-BFM 81 and 83. In ALL-BFM 81, SR patients (RF less than 1.2) were randomized to receive 18 Gy cranial irradiation or intermediate-dose i.v. methotrexate (ID-MTX) (4 x 0.5 g/m2). In ALL-BFM 83, the SR group was further subdivided into group SR low (SR-L, RF less than 0.8) and group SR high (SR-H, RF 0.8 - less than 1.2). SR-L patients received no irradiation, and were tested by randomization for the effectiveness of an intensive reinduction regimen (protocol III). SR-H patients were randomized for 12 or 18 Gy. The results were as follows: In patients of both trials with RF less than 0.8, radiotherapy could be replaced by ID-MTX plus protocol III. Without protocol III, relapses increased from 15.7% to 31.7%. Concomitantly, the fraction of relapses with CNS involvement increased from 26.7% to 36.4%. However, SR patients with RF between 0.8 and 1.2 could not be protected by reinduction alone (isolated/overall CNS relapse rate with irradiation, 4%/5%; without irradiation, 11%/22%). Dosages of 12 and 18 Gy were found to be equally protective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction.

To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height.

Adolescent↗
PubMed1989

Prognostic significance of Auer rods in childhood acute myelogenous leukemia: results of the studies AML-BFM-78 and -83.

The prognostic significance of Auer rods in predicting response rate and remission duration was investigated in 257 patients of the two West German acute myelogenous leukemia (AML) studies BFM-78 and -83. Auer rods were found in 129 children (50%) in the initial bone marrow smear. The incidence was higher in myeloid subtypes M1 (63%) and M2 (78%) compared with subtypes M4 (47%) and M5 (5%) with monocytic differentiation. In both studies, the remission rate was significantly higher in patients with Auer rods (P = 0.01), and in the study AML-BFM-83 a significantly longer remission duration was evaluated for Auer rod-positive patients (P = 0.007). In the M1 type, Auer rods were of high prognostic significance regarding both the induction success (P = 0.003) and the remission duration (P = 0.004), whereas no significant differences between Auer rod-positive and -negative patients in other subtypes were found. Occurrence of Auer rods was independent of hyperleukocytosis, the most powerful prognostic parameter in the studies AML-BFM-78 and -83, whereas absence of Auer rods was associated with the AML risk group M5. In the M1 type, Auer rod-negative leukemias appears to represent cases of poorly differentiated AML. Auer rods were therefore useful in differentiating between patients with a poor and a more favorable prognosis, particularly in the M1 type.

Adolescent↗