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G Schellong

Publications and source records attributed to G Schellong.

At least 19 recordsLinked to original sources
PubMed2005

Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials.

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Münster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 50+/-2, 61+/-3 and 57+/-2%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapy-related death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with >70 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.

Adolescent↗
PubMed2000

Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report.

The purpose of our study was to investigate the efficacy of an acute lymphoblastic leukemia (ALL)-type treatment with moderate-dose, prophylactic cranial irradiation and without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). From April 1990 to March 1995, 105 evaluable patients, 1.1 to 16.4 years of age, with T-LBL were enrolled in study NHL-BFM 90 (non-Hodgkin's lymphoma-Berlin-Frankfurt-Munster 90). They received an 8-drug induction over 9 weeks followed by an 8-week consolidation including methotrexate (MTX) 5 g/m(2) x 4. Patients with stage I (n = 2) and II (n = 2) continued with maintenance therapy (6-mercaptopurine daily and MTX weekly, both orally) until a total therapy duration of 24 months. Patients with stage III (n = 82) and IV (n = 19) received an 8-drug intensification over 7 weeks and cranial radiotherapy (12 Gy for prophylaxis) after consolidation, followed by maintenance. Residual tumor after induction had to be resected. Patients received intensified chemotherapy if tumor regression on day 33 of induction was less than 70% or when vital residual tumor was present after the complete induction phase. With a median follow-up of 4.5 years, the estimated event-free survival at 5 years is 90% (95% confidence interval, 82%-100%). Events were 1 early death, 8 tumor failures, and 1 secondary acute myeloid leukemia. A total of 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to less than 70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. We conclude that, with intensive ALL-type chemotherapy including moderate cumulative doses of anthracyclines 240 mg/m(2) and cyclophosphamide (3 g/m(2)) and moderate-dose prophylactic cranial irradiation but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. (Blood. 2000;95:416-421)

Adolescent↗
PubMed1999

Definition of a standard-risk group in children with AML.

To define paediatric AML patients with a favourable outcome in order to design a risk-adapted therapy, we analysed 489 children under 17 years of age treated similarly in studies AML-BFM 83 and 87. 369 patients (75.4%) achieved remission. Estimated probabilities of survival, event-free survival (EFS) and disease-free survival (DFS) at 5 years were 50% (SE 2%), 43% (SE 2%) and 58% (SE 3%), respectively. Multivariate analysis revealed bone marrow blasts on day 15, morphologically defined risk groups and hyperleucocytosis to be of prognostic value. EFS at 5 years estimated for patients with < or = 5% and >5% blasts on day 15 were 56% (SE 3%) v 27% (SE 4%); for the favourable morphological subgroups (M1/M2 with Auer rods, M3 and M4eo) it was 60% (SE 4%) compared with other patients (33%, SE 3%), P (Kaplan-Meier) = 0.0001 each. Hyperleucocytosis proved to be an independent prognostic factor, indicating a high risk, especially for early failure. The specific karyotypes t(8;21), t(15;17) and inv16 were closely related to the favourable morphology and outcome was in the same range. We conclude that for the definition of a standard-risk group a combination of morphological and response criteria may be sufficient. The standard-risk group defined by favourable morphology and a blast cell reduction on day 15 (not required for M3) comprises 31% of all patients, P survival, pEFS and pDFS at 5 years were 73% (SE 4%), 68% (SE 5%) and 76% (SE 4%), respectively.

Acute Disease↗
PubMed1999

High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group.

PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.

Adolescent↗
PubMed1998

The effects of etoposide on testicular function in boys treated for Hodgkin's disease.

BACKGROUND: Testicular dysfunction with elevated follicle-stimulating hormone (FSH) levels (indicating oligospermia and/or azoospermia) is a major late sequelae after treatment for Hodgkin's disease (HD) with high cumulative doses of procarbazine, cyclophosphamide, or chlorambucil. Etoposide is a newer antineoplastic agent that is effective in the treatment of HD. However, little is known regarding its testicular toxicity, especially in the pediatric age group. METHODS: The authors evaluated testicular function in 46 young adults in first continuous complete remission after stage-dependent treatment for HD with the vincristine, etoposide, prednisone, and doxorubicin (OEPA) or OEPA/cyclophosphamide, vincristine, procarbazine, and prednisone [COPP] chemotherapy regimens and involved field irradiation, excluding patients with ilioinguinal radiotherapy. Pubertal development was documented and a standardized intravenous gonadotropin-releasing hormone test was performed measuring testosterone and basal and stimulated levels of FSH and luteinizing hormone (LH). RESULTS: Testicular volumes, Tanner stages of pubic hair, and genital development were found to be appropriate or slightly delayed for the patients' chronologic age. All 27 patients had normal basal levels of FSH and LH after treatment of Ann Arbor Stage I-IIA HD with 2 courses of OEPA. Stimulated FSH and LH levels were found to be elevated only in rare patients, thus indicating normal endocrine function and spermatogenesis. However, basal and stimulated FSH levels were outside the +2 standard deviation range in 37.5% and 83.3% of patients receiving 2 cycles of OEPA and 2 cycles of COPP chemotherapy, and in 36.4% and 66.7% of patients receiving 2 cycles of OEPA and 4 cycles of COPP chemotherapy, demonstrating a high risk of oligospermia or azoospermia with these regimens. Basal LH levels essentially were normal, whereas stimulated LH levels frequently were elevated. CONCLUSIONS: Testicular function was found to be normal in patients with Stage I-IIA HD when etoposide was used in combination with vincristine, prednisone, and doxorubicin (2 cycles of OEPA). Additional chemotherapy with cyclophosphamide and procarbazine (2 cycles of OEPA and 2 or 4 cycles of COPP) negatively affected spermatogenesis and possibly Leydig cell function in a considerable number of patients. This major gonadotoxic effect most likely is due to procarbazine, although an additional effect of etoposide and cyclophosphamide cannot be excluded.

Adolescent↗
PubMed1998

Pediatric Hodgkin's disease: treatment in the late 1990s.

BACKGROUND: For two decades now combined chemo-radiotherapy has been preferred in most of the studies on childhood Hodgkin's disease (HD), because combined modality is the precondition for (1) reducing the radiation dose, (2) reducing the radiation fields, (3) shortening chemotherapy, (4) omitting splenectomy and laparotomy, and thus, for optimizing the benefit/risk ratio between cure rates and late effects. Recently, the rationale for this approach was strengthened by worrisome data about the increasing incidence of secondary breast cancer in women treated for HD in childhood, adolescence or adult age < 30 years. Nearly all breast cancers were localized in the former radiation field, and the relative risk was much higher after doses > 40 Gy than after lower doses. These findings suggest that pediatric therapy approaches abandoning radiotherapy alone with its high doses and large fields should be extended to adolescents treated outside of pediatric studies and to adults younger than 30. The risk of chemotherapy-related secondary leukemias can be limited to < 1% by omitting mechlorethamine and restricting the cumulative doses of other drugs with leukemogenic potential, as demonstrated by the experience with ABVD and the recently published data of the German-Austrian pediatric group. PATIENTS AND METHODS: The updated results of the German-Austrian multicenter study HD-90 are presented in this paper (578 patients < 18 years, follow-up: median 4 years, maximum 7 years). Patients were allocated to three treatment groups (TG) according to disease stage. In all three TG, induction procarbazine, prednisone, adriamycin) for girls and two cycles of OEPA (etoposide instead of procarbazine) for boys. Patients of TG 2 and 3 additionally received two or four cycles of COPP (C, cyclophosphamide), respectively. CT was followed by radiotherapy to the involved sites (reduced fields if possible) of 25, 25 and 20 Gy in the 3 TG, respectively. PRELIMINARY RESULTS: For the total group of 578 pats, overall survival (OS) at 5 years is 98% and event-free survival (EFS) 91%. In TG 1, EFS for girls (2 OPPA) is 96%, and for boys (OEPA), 94%, in TG 2 and 3 (combined), 92% and 86%, respectively. Secondary leukemias were not observed so far, thirty-one male patients of TG 1 who were tested endocrinologically showed normal FSH levels. CONCLUSIONS: The especially high efficacy of OPPA and OPPA/COPP could be confirmed in study HD-90 with reduced radiation doses and fields. OEPA and OEPA/COPP CT also produced very favorable results, not significantly different from those with OPPA and OPPA/COPP. It may be anticipated that the ratio between cure rates and risks of late effects of study HD-90 will compare favorably to approaches of other groups. It would be useful for the future continued optimization of HD therapy to attain a rough consensus at an international level about principles which should be considered for pediatric approaches. Some proposals have been made for treatment of early stages.

Adolescent↗
PubMed1997

Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group.

BACKGROUND: In the last two decades, it has become evident that secondary leukemias after Hodgkin's disease (HD) are mainly caused by the treatment with alkylating agents, especially mechlorethamine. Since 1978, the German-Austrian trials for childhood HD have used combined chemoradiotherapy without mechlorethamine. PATIENTS AND METHODS: The risk of secondary hematologic malignancies (SHM) was assessed in the total cohort of 667 children treated in four consecutive German-Austrian trials between 1978 and 1990. Primary chemotherapy for stages IA/B and IIA consisted of two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) or OPA (without procarbazine) and, for more advanced stages, of two cycles of OPPA or OPA plus two, four, or six cycles of COPP or COMP (C, cyclophosphamide; M, methotrexate). Radiotherapy was given in the first study to extended fields, and in later trials to involved fields only. In 591 patients, only primary therapy was given; 76 patients (11%) needed additional salvage therapy. The actuarial survival rate at 15 years is 94%. RESULTS: SHM developed in 5 of 667 patients: four acute myeloid leukemias (AMLs) and one myelodysplastic syndrome (MDS). The estimated cumulative risk for SHM at 15 years is 1.1% (95% CI, 0.0% to 2.2%). Salvage therapy was a significant risk factor for SHM (relative risk, 7.25; P = .03), whereas age, sex, stage of HD, splenectomy, and amount of alkylating agents were not. CONCLUSION: The observed risk of SHM is smaller than in other studies (adults and children) in which chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was given. This difference can be attributed to the lower cumulative doses of alkylating agents, the absence of mechlorethamine in the chemotherapy, and the small number of patients who needed salvage therapy in the presented cohort. In general, differences in the incidence of SHM after HD reflect complex differences between treatment strategies.

Adolescent↗
PubMed1996

Treatment of children and adolescents with Hodgkin's disease: the experience of the German-Austrian Paediatric Study Group.

In treatment strategies adapted to the specific problems in children with Hodgkin's disease (HD) high priority has been given to the reduction of late effects caused by radio- and chemotherapy, without sacrificing high survival rates. Combined modality treatment, as a standard option, has enabled reduced doses and fields of radiotherapy and lower cumulative total doses of critical cytotoxic agents. In Germany and Austria 1242 children and adolescents with HD have been treated in five consecutive multicentre studies since 1978. The main general objectives were to determine the extent to which radio- and chemotherapy can be reduced within a combined modality treatment concept and to find an effective chemotherapy of low long-term toxicity. Mechlorethamine in MOPP was replaced by adriamycin (OPPA) in the first 2 cycles of CT and by cyclophosphamide (COPP) in the additional cycles. The total number of cycles was reduced for early and intermediate stages. From the second study (HD-82) onward, patients were allocated to three treatment groups (2, 4 or 6 cycles, respectively) according to disease stage, and involved-field instead of extended-field irradiation was given. With radiation doses of 35, 30 and 25 Gy, high rates for event-free survival (97, 92 and 85%, respectively) at 14 years were achieved, demonstrating that microfoci in adjacent fields are safely eradicated by the chemotherapy used. Late effects of OPPA and OPPA/COPP: the cumulative risk of secondary leukaemias in 686 patients after 15 years was 0.9% for all patients and 0.8% for those who remained in first remission. Cardiomyopathies have not been observed (cumulative total dose of adriamycin 160 mg/m2). Increased FSH-levels indicating impaired spermatogenesis were found in 40% of the male patients without relapse. The prevalence was related to the number of procarbazine containing cycles (29% after 2 cycles, 46% after 4, and 63% after 6). In study HD-90, procarbazine in OPPA was replaced by etoposide (OEPA) for the boys (cumulative dose 1000 mg/m2), whereas girls received OPPA again. In TGs 2 and 3, both boys and girls received an additional 2 or 4 COPP cycles. Standard doses of involved-field irradiation were reduced to 25, 25 and 20 Gy. The preliminary evaluation after nearly 5 years reveals that the reduction in radiation doses did not affect the results with OPPA and OPPA/COPP chemotherapy. In localized stages, 2 OEPA (boys) and 2 OPPA (girls) cycles produced identical results. An additional objective of the German-Austrian trials was to re-evaluate the relevance of exploratory laparotomy and splenectomy within a combined modality treatment concept for all patients. While all children were laparotomized and splenectomized in the first study, the frequency of splenectomy and laparotomy was reduced step by step on the basis of retrospective analyses of the study data regarding infra-diaphragmatic involvement. Splenectomy has been completely abandoned since 1990. In conclusion, the ratio of cure rates and late effects has been favourably balanced with OPPA and OPPA/COPP plus low-dose involved-field irradiation, especially in female patients. In boys, the risk of testicular dysfunction can be further reduced by substituting OEPA for OPPA. Age up to 18 years does not appear to bear any prognostic significance for the treatment results under the conditions of the therapy concept described.

Adolescent↗
PubMed1996

The balance between cure and late effects in childhood Hodgkin's lymphoma: the experience of the German-Austrian Study-Group since 1978. German-Austrian Pediatric Hodgkin's Disease Study Group.

BACKGROUND: For more than 20 years now treatment strategies geared to the specific problems in children with Hodgkin's disease (HD) have been tested by different pediatric oncologic groups. In these approaches high priority was given to the reduction of late effects caused by radio- and chemotherapy, next to the goal of achieving high survival rates. Combined modality treatment as a standard option has enabled reduced dosages and fields of radiotherapy and lowered cumulative total doses of critical cytotoxic agents. METHODS: In Germany and Austria more than 1,200 children and adolescents with HD have been treated in 5 consecutive multicenter studies since 1978. The main general objectives were to determine the extent to which radio- and chemotherapy can be reduced within a combined treatment concept and to find an effective chemotherapy (CT) of low long-term toxicity. Nitrogen-mustard in MOPP was replaced by adriamycin (OPPA) in the first 2 cycles of CT and by cyclophosphamide (COPP) in the additional cycles. The total number of cycles was reduced for early and intermediate stages. From the second study (HD-82) onward, patients were allocated to 3 treatment groups (2, 4, 6 cycles, respectively) according to disease stage, and involved-field irradiation (IFI) was given instead of extended-field irradiation (EFI). RESULTS: In study HD-82 standard doses of IFI in the 3 treatment groups (TG) after 2, 4, or 6 cycles of CT were 35, 30, or 25 Gy. In a total of 203 patients probabilities for event-free survival (pEFS) and survival (pSV) were 95% and 93% at 13 years. In the 3 TG pEFS was 97%, 92% and 85%. In an international study (SIOP-HD IV-87) 65 stage IV patients were treated according to the TG 3 schedule of HD-82 (2 OPPA, 4 COPP, 20 Gy IFI). After 7 years pEFS is 77% and pSV 93%. Late effects of OPPA respectively, OPPA/ COPP: The cumulative risk for secondary leukemias after 10 years is 0.5% for all patients and 0.3% for those who remained in first remission. Cardiomyopathies have not been observed (cumulative total dose of adriamycin 160 mg/m2). Increased FSH-levels indicating impaired spermatogenesis were found in 40% of the male patients without relapse. The frequency was related to the number of procarbazine containing cycles (29% after 2 cycles, 46% after 4, and 63% after 6). In study HD-90, procarbazine in OPPA was replaced by etoposide (OEPA) for the boys (cumulative dose 1,000 mg/ m2), whereas girls received OPPA again. In TG2 and 3, both boys and girls received COPP. Standard doses of IFI were reduced to 25, 25, and 20 Gy. The preliminary evaluation after nearly 5 years reveals that the reduction of radiation doses did not impair the results after OPPA and OPPA/ COPP. In localized stages 2 OEPA (boys) and 2 OPPA (girls) produced the same results. In the 15-18 years age group compared to the younger patients identical values for pEFS were achieved. CONCLUSIONS: The ratio between cure rates and late effects has been favourably balanced with OPPA, respectively, OPPA/COPP plus low-dose IFI, especially in female patients. In boys the risk of testicular dysfunction can be further reduced by substituting OEPA for OPPA. Age up to 18 years does not appear to be of any significance for the treatment results with our therapy concept.

Antineoplastic Combined Chemotherapy Protocols↗
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↗