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Biomedical subjects

G Schellong

Publications and source records attributed to G Schellong.

At least 19 recordsLinked to original sources
PubMed1995

Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87.

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.

Acute Disease↗
PubMed1994

Hodgkin's disease in children: combined modality treatment for stages IA, IB, and IIA. Results in 356 patients of the German/Austrian Pediatric Study Group.

UNLABELLED: 356 children below 16 yrs of age with CS/PS IA, IB, and IIA were treated in the studies HD-78, HD-82, HD-85, HD-87, and OEPA-pilot 87 between June 1978 and Sept 1990. All patients received combined modality treatment (CMT) with 2 courses of chemotherapy (CT). In HD-78 and HD-82, the MOPP-derived drug combination OPPA (ADR instead of mechlorethamine) was applied. Extended-field radiotherapy (RT) was given in HD-78 using 36-40 Gy to involved-fields (IF) and 36-40 Gy vs. 18-20 Gy to adjacent fields. In HD-82 only IF-RT was applied using 35 Gy. When gonadotoxic effects of procarbazine (PC) in boys was detected in follow-up examinations, this drug was eliminated in studies HD-85 and HD-87 (OPA). Dosages of IF-RT were 35 Gy in HD-85 and 30 Gy in HD-87. With HD-87 a simultaneous pilot study was initiated to test the new combination OEPA (E = etoposide) together with 25 Gy IF-RT. RESULTS: (May 1993): Rates for event-free survival and survival are HD-78 (73 patients): 0.90 and 0.97 at 10 yrs; HD-82 (100 patients): 0.98 and 1.0 at 10 yrs; HD-85 (53 patients): 0.85 and 0.98 at 8 yrs; HD-87 (104 patients): 0.85 and 0.99 at 6 yrs; OEPA-pilot (26 patients): 0.96 and 0.96 at 5 yrs. No secondary leukemias, MDS, or solid tumors were observed in 14-yr observation time. After 2 OPPA, elevated FSH levels indicating impaired spermatogenesis were found in 29% of male patients. In contrast, after 2 OPA (without PC) only normal FSH levels were observed. In female patients, no gonadal dysfunction was found. Subclinical hypothyroidism was seen only after RT doses of > 30 Gy to the neck. Cardiomyopathies were not observed. CONCLUSION: 2 OPPA plus IF-RT using < 30 Gy can presently be considered optimal therapy for girls with localized HD. 2 OEPA plus 25 Gy IF-RT are being evaluated for boys in a phase III study (HD-90). In summary, there are good reasons to use CMT in early stages of HD in children, provided a highly effective CT of short duration and low long-term toxicity with low-dose IFI is applied.

Adolescent↗
PubMed1993

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

PURPOSE: One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS: Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS: In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION: These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

Adolescent↗
PubMed1992

Tubular function and histological findings in ifosfamide-induced renal Fanconi syndrome--a report of two cases.

Two patients developed renal Fanconi syndrome (RFS) after intensive long-term chemotherapy for metastatic Ewing sarcoma and disseminated neuroblastoma. Whereas RFS was diagnosed in patient 1 before he developed osteomalacia, patient 2 experienced severe rickets and growth retardation. Renal function studies revealed slight glomerular impairment and severe tubular defects leading to increased excretion of glucose, amino acids, inorganic phosphate and low molecular weight proteins, indicating proximal tubular damage. Patient 2 additionally showed distal tubular dysfunction with acidosis and diminished concentrating capacity. Renal biopsy in patient 1 revealed marked proximal tubular defects without interstitial lymphocytic infiltration. In both patients renal damage could most likely be ascribed to previous ifosfamide (IFOS) therapy. Our patients showed no improvement in renal function after cessation of IFOS treatment, indicating a poor prognosis of once established RFS after IFOS therapy. Measurement of tubular reabsorption capacities provides exact information on the extent of tubular toxicity induced by IFOS and may be used to monitor IFOS treated patients.

Adolescent↗
PubMed1992

Treatment of children with Hodgkin's disease--results of the German Pediatric Oncology Group.

Six hundred sixty-seven children under age 16 were enrolled in 4 consecutive studies in West Germany between 1978 and 1990. These trials were mainly designed to reduce the long-term sequelae of high dose extended-field irradiation as well as the late effects of chemotherapy, in the context of combined modality treatment for all stages. Treatment concepts and results of studies HD-82, HD-85 and HD-87 are presented here. Patients with stages IA/B and IIA were treated with 2 cycles of OPPA (HD-82, n = 100) or OPA without procarbazine (HD-85, n = 53; HD-87, n = 104), followed by involved field irradiation (IFI) using 35 Gy (HD-82, HD-85) or 30 Gy (HD-87). Kaplan-Meier estimates (KME) for event-free survival (survival) at 4.5 years are 99% (100%) in HD-82, 85% (98%) in HD-85 and 88% (100%) in HD-87. Thus, 2 x OPPA is a highly effective chemotherapy eradicating occult microfoci in the non-irradiated adjacent fields, whereas 2 x OPA is less efficacious. Reduction of the radiation dose to 30 Gy (IFI) within the combined modality concept does not affect treatment outcome. About 30% of the boys treated with 2 x OPPA, but none of the girls and none of the boys treated without procarbazine (PC) showed elevated FSH-levels indicating gonadal dysfunction. No secondary leukemias and preleukemias were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Acute myelogenous leukaemia in children under 2 years--experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group.

Clinical, morphological, immunological, cytogenetical and prognostic features of 84 children under 2 years of age with AML in studies AML-BFM-78, -83 and -87 were retrospectively analysed. There was a high incidence of acute monoblastic leukaemia (FAB M5) (41 patients--49%) and acute megakaryoblastic leukaemia (FAB M7) (study AML-BFM-87: five patients--13%) in this age group. Acute monoblastic leukaemia was associated with hepatosplenomegaly, extramedullary organ manifestations and chromosomal abnormalities involving 11q23. The probability of an 11-year event-free survival of all patients under 2 years of the three studies combined was 39% (SD 6%). While the event-free survival rates of patients aged 2 years and older could be improved in studies AML-BFM-83 and -87 compared with study AML-BFM-78, overall prognosis in children under 2 years in the three consecutive studies remained unchanged. The event-free survival rate of children with acute monoblastic leukaemia in both age groups was comparable (7 yr-EFS (AML-BFM-83 and -87): much less than 2 years--43% (SD 9%), =/much greater than 2 years--33% (SD 9%); P much greater than 0.5). This also applied to other risk groups. In conclusion, taking the high incidence of acute monoblastic and megakaryoblastic leukaemia in children under 2 years into account, no significant differences between children under 2 years or older children concerning response to therapy and overall prognosis could be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
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↗