Morbus Hodgkin as a second malignancy in acute lymphoblastic leukaemia (author's transl)]

19 months after the clinical manifestation of acute lymphoblastic leukaemia, Hodgkin's disease, stage Ia, of the cervical lymphnodes developed in a 10 year old girl during continuous complete remission of leukaemia under chemotherapy. After a regional irradiation and after completing the antileukamic therapy the patient is at present off therapy, healthy and without signs of relapse of both malignant systemic diseases. The coincidence of acute lymphoblastic leukaemia in children with other malignant neoplasias is rare. The expected frequency of second malignancies and the theories concerning oncogenesis are shortly reviewed.     

Clinical significance of cytochemical findings of childhood acute lymphoblastic leukaemia (author's transl)]

The initial bone marrow smeasrs of 821 children with ALL have been cytochemically analysed. (PAS-, acid phosphatase-(SPH), peroxydase-(POX), alpha-N-esterase-(EST)reaction) with regard to presenting clinical data and course of disease. Granular reactions of PAS and SPH were not meaningful in this respect. The paranuclear SPH-reaction was associated with high incidence of mediastinal mass, high peripheral blas count and male preponderance. All 5 patients with histories of more than 12 weeks duration belongs to the PAS-type of ALL (cloddy reaction). The PAS-type showed a higher incidence of CNS-leukaemia and generally a less favorable prognosis as compared to the UND-type. Thereby a high proportion of PAS positive cells, independently of other risk factors, indicates a better prognosis. The highterto neglected weak EST-reaction (Grad I and II according to L?ffler) seems to signalise a clincally distinct subtype of ALL with a younger age distribution maximum as compared to the UND-type, low incidence of risk factors, high rate of remissions lasting more than 2 years but unfavorable endprognosis.     

Unusual skeletal changes in acute lymphoblastic leukemia in children (author's transl)]

During the early phase of their disease three children with acute lymphoblastic leukemia showed unusual skeletal changes radiologically. Mainly osteolysis in the lower jaw, opacity of the sinus, decreased hight of the vertebrae, and a unilateral necrosis of the head of the femur. These skeletal alterations are much more common in other diseases than in acute lymphoblastic leukemia.     

Immunological aspects of acute lymphoblastic leukemia (ALL) in children (author's transl)]

The prognostic significance of the immunological classification of ALL in children is described. While the prognosis of patients with the most frequent O- or common-ALL (frequency 70-85%) is comparatively good, prognosis of patients with T-ALL, which is most probably identical with acid phosphatase positive ALL,and with the rare B-ALL is worse. The therapeutic implications of the immunological classification is discussed.     

Treatment and results of the first relapse of acute lymphatic leukemia in childhood (author's transl)]

In our experience the prognosis of hematological relapse in patients with acute lymphatic leukemia treated according to the Pinkel programme is very bad. It may be a little better for patients in whom relapse occurred after the end of therapy and who were submitted to intensified cytostatic treatment. The chances for achieving a second long-term remission, if the relapse is confined to the CNS, are also better. This is true particularly for those patients who in addition were given radiotherapy. In recurrence in the testes radiotherapy alone will not suffice and additional intensified cytosatic treatment should be considered.     

Necrosis of the caput femoris in complete remission of lymphoblastic leukaemia (author's transl)]

Two cases of necrosis of caput femoris in children are reported. In both of them the lesion developed three years after diagnosis of acute lymphoblastic leukaemia, but during complete remission. Possible relations of the necrosis to ALL, Prednisone-therapy or constitutional factors are discussed.     

Eosinophilia in the preleukaemic phase of acute granulocytic leukaemia (author's transl)]

The pathogenesis of a marked eosinophilia in the preleukaemic phase of an acute granulocytic leukaemia is described and discussed. An otherwise symptom-free girl 4 years of age, presented with a transient increased WBC count with eosinophilia during one year before onset of acute granulocytic leukaemia. All relevant tests for explanation of this eosinophilia proved negative. The phenomenon of transient eosinophilia with successive onset of acute granulocytic leukaemia may fit into the concept of immunological control of tumorgenesis. In the present case it is suggested that the initial eosinophilia was the manifestation of the body's fight against the first malignant leukaemic cells. Finally the immunological defence was overwhelmed and the eosinophilia disappeared with concomitant appearance of leukaemic cells.     

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48+-125+ months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.     

Hodgkin's disease during remission of acute lymphoblastic leukemia (author's transl)]

1 1/2 years after diagnosis of acute lymphoblastic leukemia, Hodgkin's disease, stage IIA of cervical lymphnodes could be verified microscopically in a 7 year old girl in continuous complete remission (of leukemia) and was treated with regional irradiation and combination chemotherapy after exploratory laporotomy with splenectomy. The patient now is off therapy, healthy and without any signs of relapse of the two malignancies.     

Relapse in acute lymphoblastic leukemia of childhood--treatment and results (author's transl)]

Twelve children with their first relapse of acute lymphoblastic leukemia who had the same initial therapy were treated on an out-patient basis. After 28 days all entered second remission. Medium remission duration was 11 months. At the end of the study seven patients were in continuous complete remission. Of the twelve children seven suffered bone marrow, two meningeal, two testicular relapses and one a combined bone marrow and meningeal relapse. Side effects were compatible with an out-patient treatment.     

Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)]

Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leuk?mieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.     

Bone marrow transplantation in a case of acute lymphoblastic leukemia (author's transl)]

In a 6-year-old girl with acute lymphoblastic leukemia, pericardial effusion and mediastinal mass remission lasted for 7 wks. only in spite of intensive chemotherapy. Bone marrow transplantation for a HL-A-identical, MLC-negative sister was attempted after antipleukemic therapy (Cytosin-arabinoside, BCNU, Cyclophosphamide) and total body irradiation, After uneventful course of engraftment complete remission was achieved for 5 1/2 months.     

Malignant mediastinal lymphoblastic lymphoma with t-cell ALL (author's transl)]

29 cases of T-cell derived lymphoblastic lymphoma and T-ALL have been analyzed. There is a striking prevalence of the male sex. In the peripheral blood we often find initially an excessive number of white blood cells combined with normal values for the other constituents in about half of the patients; This may be an expression for the rapid occurrence of leukaemia in T-cell lymphosarcoma. In addition to systemic ALL-therapy we performed X-ray irradiation of the mediastinum in 8 of our patients. This yielded to significantly longer first complete remissions. All patients with T-cell LSA/ALL with or without mediastinal mass should be treated in this manner. Cytochemically a strong focal acid phosphatase reaction was found to be acharacteristic of these cells. It has proved to be a screening method for this disease. The cells are T-cell derived and their pattern of surface markers is similar to that found in fetal thymocytes.     

Corticosteroid therapy in atopic diseases of children? (author's transl)]

Of 416 children suffering from different atopic diseases who were admitted as in-patients in a German aero-biological childrens clinic, 69.2% had previously received corticosteroid therapy. According to dermatological findings, 81.9% of these patients developed undesirable side effects. Of the children whose atopic dermatitis was treated prolonged with topical corticosteroids, also irreversible body changes developed through the transcutaneous absorptive processes, which were more evident and appeared more often in girls than in boys.     

Non-leukemic disease of the central nervous system in children with acute lymphoblastic leukemia. I. Somnolence syndrome (author's transl)]

Prophylactic irradiation of the skull and intrathecal application of methotrexate has proven to be highly effective in preventing central nervous system disease in acute lymphoblastic leukemia or non-Hodgkin-lymphoma. Prophylactic treatment may be complicated by a somnolence syndrome occuring 4--8 weaks after the end of irradiation. The main features of this clinical entity are somnolence, lethargy, dullness, anorexia, headache, and vomiting. EEG frequently displays a distinct slowing of activity. All symptoms are reversible after 3--49 days. The syndrome clearly is consequence of skull irradiation. Its metabolic basis probably is transient disturbance of myelinization.     

Occurrence of thyroid carcinoma after treatment of acute lymphoblastic leukemia (author's transl)]

A 21 month old boy with acute lymphoblastic leukemia diagnosed on 17th September 1971, was treated according to the Memphis Study VII of Pinkel. Bone marrow examination, 39 days after treatment, showed complete remission. The patient has since then been in continuous complete remission. Therapy was suspended twice (29 days and 18 days) because of interstitial pneumonia. The treatment was terminated on 9th October 1974 nearly 3 years after onset of the disease. Because of papillary thyroid carcinoma with metastases in the regional lymph nodes, a total thyreoidectomy with removal of lymphnodes was performed on 30th April 1977. Because of a relapse in the neck lymphnodes, the patient was treated in December 1977 with radioiodine. The prognosis is however not discouraging.     

Longterm therapy with i.v.-gamma-globulin in children (author's transl)]

gamma-Globulin for treatment should be injected by the intravenous route whenever possible. An unsplit molecule would be of great advantage in this context but there is the problem of antigenicity. One possibility to attain a good tolerance for i.v.-gamma-globin is to treat the molecule with beta-propiolactone. The acute tolerance and the efficacy of this preparation are proven. We wanted to find out if the modification of the immunoglobulin by beta-propiolactone would induce new antigene properties, which could lead to antibody production after repeated injections. There were no antibodies to be found neither in vivo nor in vitro in 6 children, which received 8--166 injections of this preparation.     

Complete heart block and pacemaker therapy in children (author's transl)]

The etiology of congenital and acquired complete heart block is discussed. The prognosis is much better in mostly congenital suprabifurcational blocks, than in the infrabifurcational blocks, which are acquired in most instances. Suprabifurcational blocks are characterized by normal QRS complexes, higher heart rates, and adequate frequency adaptation to exercise. Widened and deformed QRS complexes and fixed heart rates as low as 40--50 beats per minute are typical in infrabifurcational blocks. Whereas children with congenital heart blocks only eventually need pacemakers, the immediate implantation of a pacemaker is mandatory in children with acquired heart blocks after a decrease of the heart rate below 30--40 beats per minute and/or after an Adams-Stokes attack. With demand pacemakers being available, fixed rate systems are obsolete for children. Lithium batteries should be preferred for their smallness and their larger life span. A considerable body of surgical and technical problems due to infection, wire damage, and other complications still awaits solution.