[Treatment of hemophagocytic lymphohistiocytosis, HLH, with bone marrow transplantation]. / Behandlung der Hämophagozytischen Lymphohistiozytose, HLH, mit Knochenmarktransplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of infancy and young childhood. The clinical presentation includes recurrent unexplained fever with hepatosplenomegaly. Cytopenia, hypofibrinogenemia and/or hypertriglyceridemia and hemophagocytosis in bone marrow, spleen and lymphnode confirm the diagnosis. Hemophagocytosis may not be present at the beginning. In these cases, diagnosis is facilitated by a positive family history, a relapsing course of the disease, the frequent involvement of the central nervous system and positive findings on immunological work-up. Treatment by chemotherapy and immunosuppressants can achieve sustained remissions in most patients and reinduction of remission after relapse is possible. Most children however, eventually die from progressive disease. At present, allogeneic bone marrow transplantation is the only curative therapeutic option. Between August 1992 and May 1997 eleven consecutive patients with HLH received bone marrow from unrelated (n = 7) or matched sibling donors (n = 4). The conditioning regimen consisted of busulfan, VP-16 and cyclophosphamide. Patients engrafted after a median time of 16 days (13-43). Only one patient developed grade III acute GVHD, another patient, grade II acute GVHD. Although regimen-related toxicity was extensive, all patients have survived without signs of HLH after a median follow up of 20 months (8-63). One patient suffers from chronic GVHD, three patients reveal psychomotoric retardation and one patient has severe impairment with spastic tetraparesis, amaurosis and seizures. Our experience shows that HLH can be successfully treated by allogeneic BMT from unrelated donors.

Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Münster Group.

Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Münster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P=0.04), presented predominantly with the common while lacking the T immunophenotype (P=0.005), had a lower frequency of hyperdiploidy (P=0.004) and tended to have a better initial steroid response (P=0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58+/-8% vs 70+/-1%, P=0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65+9% vs 70+/-1%, P=0.66) or were <6 years of age, irrespectively of therapy modifications (73+/-9% vs 74+/-1%, P=0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P=0.0107), but was not prognostic at diagnosis (P=0.103). Age > or = 6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.

[Malignant melanoma in the child--2 case reports]. / Malignes Melanom beim Kind--2 Fallberichte.

Case histories of two infants with malignant melanoma are presented. Both tumors had developed from a congenital mole to advanced disease with lymph node metastasis at time of diagnosis, findings which are commonly correlated with poor outcome. Initially, both patients were surgically treated. From the experience with few described cases of melanoma in childhood and with a large number of adult patients, neither chemotherapy and conventional BCG immunotherapy nor irradiation seem to be an effective treatment and are accompanied by many adverse side effects. Therefore in one patient therapy was limited to surgery alone. In the other child it was followed by treatment with high-dose recombinant alpha-2-interferon (1 Mill. i.u./Kg X d) plus an H2-receptor antagonist. Unexpectedly this girl developed neurological side effects, characterized by spastic paraparesis, indicating damage to the first motoneuron. All symptoms completely resolved after discontinuation of drugs within three months. Both children have been in complete remission for 18+ and 32+ months, respectively.

[Which is the best methotrexate schedule for maintenance therapy of childhood ALL? A randomized study]. / Randomisierte Studie zur Methotrexatapplikation in der Erhaltungstherapie der akuten lymphoblastischen Leukämie im Kindesalter.

58 children were admitted to a prospective randomized leukemia induction and CNS-prophylaxis three different protocols were followed for maintenance. A (n = 20): 6-MP (50 mg/m2) p.o. daily + MTX (20-30 mg/m2) p.o. weekly; B (n = 20): 6-MP (50 mg/m2) p.o. daily + MTX (75-150 mg/m2) i.v. every two weeks; C (n = 18): 6-MP (50 mg/m2) p.o. daily + alternating 8-week-courses of four biweekly i.v. injections of MTX (75-150 mg/m2) and four biweekly i.v. injections of Cyclo (600 mg/m2). After all patients have been followed for at least 48 months, the rates of continuous complete remission are 42% in protocol A, 63% in protocol B, and 29% in protocol C. No encephalopathies have been observed with regimen B.

[Intestinal yersiniosis: 25 cases of infections with Yersinia pseudotuberculosis and Yersinia enterocolitica (author's transl)]. / Enterale Yersiniose: 25 Beobachtungen von Infektionen mit Yersinia pseudotuberculosis und Yersinia enterocolitica.

Yersinia infections in 16 adults and 9 children are reported. 15 cases were caused by Yersinia pseudotuberculosis, 8 of them were proved by serological findings. In 4 cases the infection by Yersinia pseudotuberculosis was likely, in 3 other cases possible only. Real infections caused by serotype IV are demonstrated too. Furthermore there were 10 cases caused by Yersinia enterocolitica, 3 of them were proved by bacterial, the other ones by serological findings. Both germs caused identical symptoms: fever (80%), abdominal pains (56%), diarrhoea (52%), erythema nodosum (44%), arthritis (40%), vomiting (16%), weight loss (16%), lymphoma (12%) and others. In children 50% of erythema nodosum was produced by intestinal yersiniosis. The beginning with gastroenteritis and fever mostly was followed by a second phase with returning fever, abdominal pains, erythema nodosum and/or arthritis. Antibiotic therapy had a definite effect only in the first phase of gastroenteritis and in the two possibly relapsing cases. In two of 5 patients with long standing arthritis the HL-AB 27 was present.