Childhood biphenotypic leukemia: detection of mixed lymphoid and myeloid populations in bone marrow specimens.

In a retrospective study, consecutive bone marrow biopsies and smears from 104 children with leukemia were analyzed for expression of lymphoid and myeloid lineage-associated features. Eighty-six cases were diagnosed as acute lymphoblastic leukemia (ALL), 14 cases as acute non-lymphocytic leukemia (ANLL), and one case as chronic myelogenous leukemia (CML). Finally, three children were classified as biphenotypic leukemia demonstrating mixed populations of lymphoid and myeloid blast cells from the onset of the disease. Thus, leukemia with a dual phenotype was assessed in 2.9% of all cases examined. The recognition of bilineage origin even by conventional methods such as morphology, cytochemistry and marker studies may be important for the selection of an effective treatment.

[Primary intracranial germinoma. Problems in determining the diagnosis exemplified by 4 cases]. / Das primäre intrakranielle Germinom. Probleme der Diagnosefindung am Beispiel von vier Fällen.

Primary intracranial germinoma is a possible cause of "idiopathic" diabetes insipidus in childhood and adolescence. The histopathologic appearance can be similar to inflammation, and may delay the final diagnosis. Further diagnostic difficulties are demonstrated by the use of anamnestic and clinical data as well as diagnostic imaging findings in four children with histologically proven primary intracranial germinoma.

Pancreatoblastoma in children. Case report and review of the literature.

Pancreatolblastomas are rare embryonal malignancies in childhood. We report a 3-year-old girl with a tumor of the head of pancreas. Staging by bone scintigraphy and CT scans of abdomen and chest did not show evidence of metastatic disease. Tumor markers showed elevated levels of alpha-1 fetoprotein (64 ng/ml; normal 0-10 ng/ml) and lactate dehydrogenase (423 U/l; normal range below 300 U/l). The tumor was macroscopically completely removed by local resection. Postoperative tumor grading was pT1, NO, MO. The child recovered very soon after surgery without severe complications. Tumor markers dropped to normal values, indicating complete remission (follow-up time 12 months). According to the biological growth characteristics of pancreatoblastomas and to the literature, localized and non-metastatic tumors should be completely resected without radical pancreatoduodenectomy and without adjuvant chemotherapy. This is the most conservative therapy with a good prognosis. However, metastatic disease, primarily inoperable conditions or local relapses are indications for chemotherapy combined with radiotherapy and followed by resection of the tumor. At present, the prognosis of such cases is rather poor.

[A child-centered management concept for families of children with cancer in the terminal phase. Cooperation with the established physician]. / Kindzentriertes Betreuungskonzept für Familien krebskranker Kinder in der Sterbephase. Zusammenarbeit mit dem niedergelassenen Arzt.

For a period of more than a year children with incurable diseases and their families we observed at home during the final stage of the children's illness. The psychological assistance and the necessary medical care were guaranteed by the staff of the district attending clinic, the family doctors and the district home nurses. The results of this project show that the concept which takes into account the child's welfare at home, was practicable in all cases even in very serious disease right up to death.

[High-dose chemotherapy: principles, indications and complications]. / Hochdosierte Chemotherapie: Grundlagen, Indikationen, Komplikationen.

Cure rates of children and adolescents with malignant diseases have improved since the introduction of systemic chemotherapy in cooperative trials in the recent 10 to 15 years. Tumors resistant to conventional doses have responded to high dose regimens. The rationale for the use of high dose regimens is discussed as well as adequate methods of protecting against severe and often lifethreatening complications.

Myositis ossificans traumatica in young children: report of three cases and review of the literature.

Myositis ossificans traumatica (MOT) is a rare musculoskeletal disorder in young children. Clinical and imaging presentation in the early stage of disease makes it difficult to differentiate between infection and musculoskeletal neoplasms, particularly in the absence of a history of trauma. Three cases of MOT in children under the age of 10 years, two with inferential trauma, are presented and the findings on different imaging modalities are discussed with reference to the existing literature. While findings based on a single imaging technique, including MRI, may be rather non-specific and even misleading, the combination of different modalities can assist in the consideration of MOT as a possible diagnosis. For example, the demonstration of soft-tissue haematoma on US would suggest the traumatic origin. A rational imaging approach is proposed.

[Clinical experiences with polyethylene glycol-bound E. coli L-asparaginase in patients with multiple recurrences of acute lymphoblastic leukemia]. / Klinische Erfahrungen mit polyäthylenglykol-gekoppelter E. coli-L-Asparaginase bei Patienten mit ALL-Mehrfachrezidiv.

The efficiency and toxicity of E. coli-L-Asparaginase coupled to polyethyleneglycol (PEG-ASP) was investigated in 5 patients with second relapse of acute lymphoblastic leukemia. PEG-ASP was administered at a dose of 2000 U/m2 as infusion over 2 hrs. every 2 weeks. Following an initial single agent phase, PEG-ASP was combined with prednisone, vincristine, adriamycin and methotrexate i.t. Following induction, all 5 patients were in third remission. The remissions lasted from 3 to 9 months, median 4 months. The toxicity was transient and mild. Also in patients sensitized against native L-Asparaginase no anaphylactic reactions were observed.

(11; 14) translocation in three boys with acute lymphoblastic leukemia of T-cell immunophenotype.

Three boys, 12, 15 and 5 years old are presented with acute lymphoblastic leukemia resp. Non-Hodgkin's lymphoma with leukemic transformation. Blast cells could be characterized as being of T-cell origin. Hand mirror variant was the predominant morphologic feature of the blast cells in two patients. Chromosome analysis of the leukemic blast cells revealed a pseudodiploid (modal chromosome number = 46) karyotype in two patients and a pseudotetraploid (modal chromosome number = 92) in one patient. A chromosome translocation (11; 14) with breakpoints at (p 13; q 13) (within the human T-cell receptor alpha chain locus!) was found in the leukemic cells of all three cases plus an additional t (7; 9) (q 22; p 13) in one patient.

[Hepatitis B infections in cytostatically treated children]. / Hepatitis-B-Infektionen bei zytostatisch behandelten Kindern.

Between Nov. 83 and Oct. 84 15 children under chemotherapy for malignant diseases, 2 relatives and 2 nurses developed hepatitis-B antigen seropositivity. Epidemiological studies gave evidence for non-parenteral spread of the infection. The course of the disease was usually asymptomatic or mild. Amongst the patients who developed hepatitis-B there was a considerable number of children who had presented with a recurrence of their malignant disease. Two characteristic cases of hepatitis B are presented showing the wide range of clinical manifestations of this disease in immunocompromised children with ALL.

[Cellular immunity using skin tests in children with malignant diseases at the time of diagnosis and after therapy]. / Untersuchungen zur zellulären Immunität mittels kutaner Reaktion bei Kindern mit bösartigen Erkrankungen zum Diagnosezeitpunkt und Therapieende.

Patients with cancer often have disturbances of cellular immunity. Changes of cellular immunity are frequently associated with tumor progression or an increased risk of a relapse. Cellular immunity is studied with an in vivo test system using 7 different recall antigens. We studied the cutaneous reaction of 80 children with various malignant diseases at time of diagnosis, at the end of the chemotherapy or prior to a relapse of the disease using the multitest Merieux. Before starting treatment patients with systemic diseases showed only a little response to the recall antigens. Patients with solid tumors had normal responses. No prognostic meaning of the multitest results were seen, if it was done before starting the treatment. At time of a relapse, these patients mostly had negative skin reactions using the multitest. It has to be studied if these results show a new systemic disease or if they are expression of an ongoing disturbance of cellular immunity of these patients.

Microbial spectrum of blood and body cultures in febrile episodes of children under chemotherapy for treatment of malignant diseases.

One hundred thirty-five febrile episodes in 111 children with malignancies were reviewed. In 50 of 125 episodes blood cultures were positive; gram-positive bacteremia was detected in 40 episodes and gram-negative bacteremia in 10 episodes. The predominant gram-positive bacteria were coagulase-negative staphylococci, the predominant gram-negative bacteria were Escherichia coli. The possible role of coagulase-negative staphylococci in causing septicemia in immunocompromised hosts is discussed with conclusions that influence designing a primary antibiotic regimen to treat febrile episodes in leukopenic children.

[Experiences with the combination carboplatin/VP 16 in the treatment of recurrent tumors in children]. / Erfahrungen mit der Kombination Carboplatin/VP16 in der Behandlung rezidivierter Tumoren im Kindesalter.

The efficiency and toxicity of Carboplatin, a derivate of cisplatin in clinical use since 1981, was investigated in combination with VP16 in 11 children with recurrent or refractory tumors. 10 patients received therapy as outpatients without hydration. 160 mg/m2/day of Carboplatin were administered days 1 to 3, or days 1 to 5 as one hour infusion, combined with VP16 100 mg/m2/day, days 1 to 3, or days 1 to 5 as one hour infusion. One patient received Carboplatin, 600 mg/m2, as 24 hrs. continuous infusion in combination with VM26, 150 mg/m2/day as one hour infusion, 8 hours after Carboplatin. 9 of the treated children had measurable disease. 3 of 9 patients achieved a tumor response of more than 50% (partial remission). 5 of 9 children showed tumor response of less than 50% (stable disease). 1 out of 9 patients had progressive disease. 8 of 9 patients reported improvement or disappearance of clinical symptoms after the first course. All patients had severe myelosuppression with different times to recover. The WBC nadir was 14 days after Carboplatin/VP16. The nadir platelet counts occurred 21 days after therapy with fast recovery. Non-hematological side effects were minimal.

[Immune stimulation with interleukin-2 after autologous stem cell transplantation in children and adolescents with solid tumors]. / Immunstimulation durch Interleukin 2 nach autologer Stammzelltransplantation bei Kindern und Jugendlichen mit soliden Tumoren.

Children with solid tumors of poor prognosis have benefitted from autologous bone marrow transplantation as a treatment modality. Adjuvant interleukin-2 (IL2) therapy has previously been shown to improve prognosis in adults with some solid tumors. In this setting improved survival probability has been attributed to IL2-mediated augmentation of antineoplastic activity of the immune system. In this study 8 pediatric patients in complete remission after autologous stem cell transplantation were treated with recombinant IL2 administered in 3 cycles of 5 days continuous intravenous infusions and a two week rest in between. We demonstrated that IL2 therapy increased transplantation-related activation of the immune system both on cellular and humoral levels. Peripheral blood T and NK cell number increased by the factors 1.7 and 6.0 respectively. NK and T cell activation were further enhanced as indicated by elevated levels of soluble IL2 receptor. The production of tumor cytotoxic cytokines like alpha TNF and gamma INF was stimulated. The elevated aTNF and gamma INF cytokine synthesis seemed to be mainly related to the activation and proliferation of NK cells, as T cells obtained from patients after IL2 therapy showed a definite cytokine production deficiency after T cell specific stimulation.

[Thrombosis in children with acute lymphoblastic leukemia treated with the COALL protocol]. / Thrombosen bei Kindern mit akuter lymphoblastischer Leukämie unter dem COALL-Protokoll.

To see whether the clinical manifestation of thrombotic events or hemorrhagic infarctions appears as a relevant problem when treating children with acute lymphoblastic leukemia (ALL) concerning the COALL therapy-protocol, we started an inquiry of the participating hospitals. The mentioned protocol was designed by the German Society for Pediatric Oncology and Hematology to treat ALL in childhood. All participants gave us information about the treatment period from January 1989 to December 1992. In 6 from 286 treated patients a thromboses appeared in clinical terms. None of them was connected with a lethal outcome. There was no observation of a hemorrhagic infarction. The overall thromboses frequency was 2.1%. In 1.4% patients "symptomatic" thrombosis developed close to a continuous venous catheter, which can be considered as a thrombogene risk factor. About 0.6% (2/286) of the patients developed the thrombotic events without another risk factor. They can be regarded as "idiopathic". 1/2 idiopathic thromboses led to a life threatening situation. There are two important factors that can enhance thromboses: 1) the therapy period, especially induction therapy and application of asparaginase and 2) a continuous venous catheter. The fact that asparaginase is not used during the induction therapy is a characteristic of the COALL protocol. It seems to be useful to differentiate between "idiopathic" and "symptomatic" thrombotic events, because "symptomatic" thromboses appear also in non-leukemic diseases quite frequently.

T-cell acute childhood lymphoblastic leukemia with chromosome 14 q 11 anomaly: a morphologic, immunologic, and cytogenetic analysis of 10 patients.

Ten patients with T-cell acute lymphoblastic leukemia (ALL) and a chromosome anomaly involving band 14 q 11 are described. Mitotic index of bone marrow blasts was high in all patients (average 3.0%). Lymphoid morphology of the leukemic blasts, however, varied somewhat among the patients. The leukemic cells of 5 patients showed an immunophenotypic profile corresponding to early or common thymic differentiation stages whereas 5 children showed strong expression of CD 3 suggesting a more mature thymic phenotype. Leukemic karyotypes revealed a modal chromosome number of 46 in 9 cases, 92 in one case. A chromosome translocation t(11; 14) (p 13; q 11) was found in 5 cases, a t(1; 14) (p 32; q 11) in 2 cases, a t(10; 14) (q 24; q 11) in one case, a (hitherto undescribed) t(12; 14) (q 22; q 11) in one case, and an inv (14) (q 11 q 32) in one patient. Additional abnormalities were t(3; 10), t(7; 9), dup(7 q), del(6 q), del(10 q), and del(1 q). Of 32 cases with T-cell ALL successfully karyotyped in our laboratory 15 (= 47%) had structural aberrations involving chromosomes 1, 3, 6, 7, 9, 10, 12, 14. Ten of these 15 patients (= 67%) had a chromosome 14 q 11 anomaly. It is concluded that chromosome band 14 q 11, the gene locus of the T-cell receptor alpha-chain, is the most common site for structural chromosome aberrations in T-cell ALL.