Polymyositis--an unusual presentation of cGvHD in children.

Polymyositis is a rare manifestation of cGvHD in adult patients following allogeneic BMT. Here, we report on a 2.1-yr-old girl who presented with a facial swelling and rapidly developing respiratory failure eight months after BMT for severe combined immunodeficiency. Possible infectious agents and autoimmune origin other than cGvHD were excluded. The girl responded promptly to steroid therapy and remains well without other signs of cGvHD four months later.

Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative disorder of early childhood. In all, 21 patients with JMML who received donor leukocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) for either mixed chimerism (MC, n=7) or relapse (n=14) were studied. Six patients had been transplanted from an HLA-matched sibling and 15 from other donors. Six of the 21 patients (MC: 3/7 patients; relapse: 3/14 patients) responded to DLI. Response rate was significantly higher in patients receiving a higher total T-cell dose (> or =1 x 10(7)/kg) and in patients with an abnormal karyotype. None of the six patients receiving DLI from a matched sibling responded. Response was observed in five of six patients who did and in one of 15 children who did not develop acute graft-versus-host disease following DLI (P=0.01). The overall outcome was poor even for the responders. Only one of the responders is alive in remission, two relapsed, and three died of complications. In conclusion, this study shows that some cases of JMML may be sensitive to DLI, this providing evidence for a graft-versus-leukemia effect in JMML. Infusion of a high number of T cells, strategies to reduce toxicity, and cytoreduction prior to DLI may improve the results.

Mucinous cystadenoma of the ovary in a 15-year-old girl.

Benign neoplasms of the ovary originating from epithelial tissue are common tumors in adult women. They are, however, rarely seen in children or adolescent girls. Here the authors present a case of an ovarian mucinous cystadenoma in a premenarchal girl. To our knowledge, there are only 5 other cases reported in the literature.

Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection.

We present two male siblings suffering from recurrent manifestations of B-cell non-Hodgkin's lymphoma (NHL) and recurrent infections of the lower respiratory tract associated with bronchiectasis. Immunodeficiency could not be demonstrated by any laboratory investigation. In both patients, lymphomas developed without evidence for Epstein-Barr virus (EBV) infection, i.e. no antibody response to EBV-specific antigens, negative EBV-PCR (polymerase chain reaction) in peripheral blood cells, and absence of latent membrane protein (LMP) and EBV-encoded RNA (EBER) in lymphoma cells. Molecular analysis of the SH2D1A, the gene for X-linked lymphoproliferative disease (XLP) led to the identification of a deletion in the first exon in both patients. Therefore, we postulate that the genetic defect and the following dysregulation of the B-/T-cell interaction rendered these patients susceptible to the early onset of B-cell NHL and that EBV infection is not an obligate prerequisite.

Haemophagocytosis in early congenital syphilis.

UNLABELLED: A previously healthy male infant developed hepatosplenomegaly, severe anaemia and thrombocytopenia 5 weeks after birth. Marked haemophagocytosis was present in the bone marrow. A typical maculopapular rash suggested early congenital syphilis. The diagnosis was confirmed by serology and by the presence of untreated syphilis in both parents. CONCLUSION: Syphilis needs to be excluded in infants suspected of haemophagocytic lymphohistiocytosis.

Feasibility and response to budesonide as topical corticosteroid therapy for acute intestinal GVHD.

Therapy of acute intestinal GVHD is still one of the main challenges after allogeneic transplantation. Increasing systemic immunosuppression (IS) is the first choice and includes corticosteroids and lymphocyte antibodies, often associated with severe side-effects. In inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, topical steroid therapy is used very successfully. Because of the similarity between these and acute intestinal GVHD we conducted a trial with oral budesonide (Budenofalk), a new topically active glucocorticoid, to treat patients with acute GVHD > or = grade II. After a diagnosis of aGVHD > or = grade II, 22 patients received increased IS, mainly systemic corticosteroids, and additionally budesonide 9 mg/day divided into three doses. Improvement in aGVHD, infectious side-effects, reduction of systemic IS and outcome were documented. Results were compared with the results of 19 control patients, who were treated only by increasing IS dose. In 17/22 patients (70%), treated with budesonide, the acute intestinal GVHD resolved and no relapse occurred after decreasing the systemic IS, while continuing budesonide. In only 8/19 patients in the control group did the acute intestinal GVHD resolve and 2/8 patients had a relapse of intestinal GVHD after decreasing IS, with an overall response of 33%. No severe intestinal infections occurred. We conclude that budesonide may be effective in acute intestinal GVHD as a topical corticosteroid and prospective, randomized studies should demonstrate its efficacy in allowing reduction of systemic immunosuppressive therapy, and its side-effects.

[Bacteremic episodes in pediatric oncologic patients, especially caused by the Streptococcus viridans group]. / Bakteriämie-Episoden bei pädiatrisch-onkologischen Patienten, insbesondere durch Streptokokken der Viridans-Gruppe.

BACKGROUND: The management of infectious complications plays a major role in the care for pediatric cancer patients. The majority of infections in the neutropenic patient present as fever of unknown origin without recovering a pathogen from the blood stream. The careful evaluation of bacteremic episodes is essential, since knowledge of the bacterial spectrum expected is crucial for the successful anti-infective treatment. PATIENTS AND METHODS: From 1985 to 1995 all bacteremic episodes in pediatric oncology patients at the University Children's Hospital Freiburg were retrospectively analyzed with respect to the pathogens encountered, the antibiotic susceptibility profile and the underlying conditions. RESULTS: Overall, 113 bacteremic episodes were encountered in pediatric oncology patients, 68 of them in patients with hematological malignancies, and 45 in patients with solid tumors. In both patient groups, gram-positive bacteria were predominant with 72% and 58%, respectively. In patients with hematological malignancies, viridans streptococci were the most frequently isolated pathogens (35%) with a relevant morbidity (29% of patients developed a severe sepsis syndrome and/or ARDS), but were found only in 9% of patients with solid tumors. In 28% of patients with leukemia or lymphoma, gram-negative rods were cultured, in 6% Pseudomonas spec., in 4% Acinetobacter spec., and in 18% enterobacteria. In patients with solid tumors, in 38% gram-negative rods were isolated, 7% Pseudomonas spec., 16% Acinetobacter spec., 16% enterobacteria. In 3 patients, fungemia was observed. The antibiotic susceptibility profile was quite favorable in both, gram-positive and -negative bacteria: none of the gram-positive isolates was resistant to vancomycin, none of the Staphylococcus aureus isolates was resistant to oxacillin. All gram-negative bacteria were fully susceptible to ceftazidime, imipenem and ciprofloxacin. CONCLUSION: Gram-positive bacteria account for 2/3 of all bacteremic episodes in pediatric oncology patients. Streptococcus viridans was the most important pathogen in hematological malignancies accounting for a significant, pathogen-specific morbidity.

Testicular relapse after 13 years of complete remission of acute lymphoblastic leukemia.

Girls with acute lymphoblastic leukemia appear to have a higher cure rate than boys. This is in part attributable to the reoccurrence of testicular disease in boys. Although the frequency of testicular relapse is less than 5% with current intensive therapy regimens, testicular disease remains of apparent clinical importance. Here we report an unusually late testicular relapse in an 18-year-old male after 12.7 years of continuous complete remission, and review the literature regarding this late failure.

[Kinetics of myelopoietic regeneration and mobilization of CD34-positive cells within the scope of the NB90 Neuroblastoma Therapy Study]. / Kinetik der myelopoetischen Regeneration und Mobilisierung CD34-positiver Zellen im Rahmen der Neuroblastom-Therapiestudie NB90.

Hematological and clinical data of 14 children with neuroblastoma treated according to the German neuroblastoma therapy study NB 90 were analyzed. Therapy included 4 or 8 intensive therapy elements N1 (Etoposide 125 mg/m2 day 1-4, Vindesine 3 mg/m2 day 1, Cisplatin 40 mg/m2 day 1-4) and N2 (Vincristine 1.5 mg/m2 day 1 + 8, Dacarbazine 200 mg/m2 day 1-5, Ifosfamide 1500 mg/ m2 day 1-5, Doxorubicin 30 mg/m2 day 6 + 7) in alternating order. The hematological recovery was studied after 86 therapy elements N1/N2. G-CSF had been given in 23 therapy courses, while no cytokine was administered in 63 therapy courses. Mobilization of CD34+ cells was studied in 13 therapy courses with G-CSF. Severe myelosuppression with an absolute neutrophil count < 500/microL was noted 2-4 weeks after each therapy element. The use of G-CSF did not prevent, but shortened neutropenia. There was no difference in the number of infections nor time delay of therapy between the courses with or without G-CSF. In 11 therapy courses G-CSF was started on the day following the last chemotherapy dose (N1: day 5; N2: day 9). In 12 therapy courses G-CSF was given delayed, starting day 12 after the initiation of therapy. Kinetics of granulocyte recovery was similar in the early or delayed application of G-CSF. Neutrophil recovery after the therapy element N1 was earlier and faster compared to that of therapy element N2. The more rapid rise of the neutrophils after the N1 element was accompanied by an effective mobilization of CD34+ cells. Taking into account the limitations of this retrospective study, the data may help to optimize the application of G-CSF in a very intensive therapy study like NB90.

[Oncologic after-care--a patient-oriented concept. Basic diagnostic plan for pediatric oncology patients]. / Onkologische Nachsorge--ein patientenorientiertes Konzept. Ein Basisdiagnostikplan für pädiatrisch-onkologische Patienten.

With intensive treatment many children and young adults with cancer can be cured of their disease. Therefore, the recognition of late effects of therapy will become increasingly important. Future concepts of follow-up care in pediatric oncology will have to serve two purposes: First, to determine the status of the malignant disease with early diagnosis of relapse and second, to recognize relevant side effects of treatment. We present a comprehensive approach of follow-up care which is primarily based on the definition of risk criteria for the development of relevant organ toxicity after different treatment modalities. For each patient a standardized summary of therapy delivered is documented. According to the definition of the risk criteria an individualized schedule for follow-up is decided upon. We hope that this structured concept will result in appropriate patient care while keeping the diagnostic efforts and costs limited.