[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature]. / Supratentorieller primitiver neuroektodermaler Tumor: Erfahrungen in einem Zentrum im Vergleich zur Literatur.

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT.

Griscelli syndrome is characterized by partial albinism with variable immunodeficiency. Two different gene loci are responsible for this rare, autosomal recessive disease: the myosin Va gene and the RAB27A gene. As recently reported, only patients with mutations of the RAB27A gene suffer from immunodeficiency and hemophagocytic lymphohistiocytosis. Thus, only patients who suffer from the Griscelli syndrome with mutations of the RAB27A gene should receive BMT/PBSCT, which is the only curative therapy. Due to the risk of early relapse or severe infections, BMT/PBSCT should be carried out as soon as possible; if patients do not have HLA-identical family members, valuable time may be lost by searching for an HLA-identical unrelated donor. We report the first peripheral blood stem cell transplant (PBSCT) with T cell depletion in a 6-month-old girl with Griscelli syndrome, and a deletion of the RAB27A gene. The donor was her phenotypically HLA-identical mother. Conditioning included busulfan, VP16 and cyclophosphamide. The patient was transfused with 15.4 x 10(6)CD34-positive cells/kg and 17.6 x 10(3) CD3-positive cells/kg recipient weight. Three months after the transplant, a curable lymphoproliferative syndrome occurred. 26 months after the transplant, the patient is doing well with stable mixed chimerism (52% donor cells).

[Antiviral prophylaxis]. / Antivirale Prophylaxe.

Antiviral prophylaxis in pediatric oncology and pediatric bone marrow transplantation (BMT)/stem cell transplantation (SCT) focuses herpes viruses: herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV) since these viruses cause significant morbidity and mortality due to primary infection or to reactivation in long term latency. The majority of studies on antiviral prophylaxis, especially those on CMV-prophylaxis, have been conducted in adult patients. Recommendations for antiviral prophylaxis have been published recently by the German "Deutsche Gesellschaft für pädiatrische Infektiologie" and by the following American institutions and societies "Centers for Disease Control and Prevention", "Infectious Diseases Society of America", "American Society of Blood and Marrow Transplantation" who published the "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients". Concerning HSV- and VZV-prophylaxis there are almost no differences between recommendations of the german society and the american institutions, however recommendations for preventing CMV-disease and CMV-recurrence do differ considerably. Controversial aspects of antiviral prophylaxis, e.g. VZV vaccination or CMV prevention, should be studied in oncology and infectious diseases working groups to define consensus in the near future.

[Vaccination]. / Impfungen.

Vaccination has been an important part of antiinfectious prophylaxis in pediatric oncology comprising immunizations with special indication like varicella vaccine and follow-up of routine immunizations after chemotherapy and bone marrow transplantation (BMT). Studies from the last decade demonstrate a loss of long term immunity to immunization preventable disease in most patients with chemotherapy and BMT who had received appropriate immunization before. So far routine vaccination programs following intensive chemotherapy have not been studied prospectively. Immunization programs following BMT have shown that immunizations with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine - given at least 12 months after transplantation - are safe and effective. Vaccination with live attenuated trivalent vaccine against measles, mumps and rubella in patients without chronic "graft versus host disease" (GVHD) and without ongoing immunosuppressive therapy, performed 24 months after transplantation, proved to be safe too. Recommendations have been published by 5 different official groups: (1.) "Ständige Impfkommission" (STIKO) and (2.) "Deutsche Gesellschaft für pädiatrische Infektiologie" (DGPI) recommend varicella vaccine für children with leukemia in remission for at least 12 months, for children with solid tumors and for patients getting an organ transplantation. Both societies do not comment on the schedule of booster vaccinations (with live attenuated vaccines) after the end of chemotherapy and after BMT. (3.) "Qualitätssicherungsgruppe" der "Gesellschaft für pädiatrische Onkologie und Hämatologie" (QS-GPOH) recommends immunization with nonliving vaccines when the patient is off therapy for at least 3 months and immunization with live attenuated vaccines when he is off therapy for at least 6 months. This group does not comment on varicella vaccine which has been controversial among pediatric oncologists. (4.) The " Infectious disease working party of the European group for Blood and Marrow Transplantation" (EBMT) recommends immunization with nonliving vaccines when the patient is off transplantation for at least 12 months, without GVHD and without immunosuppressive therapy. (5.) The "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant (HSCT) Recipients" published by the following american institutions and societies: "Centers for Disease Control and Prevention", "Infectious Diseases Society of America" and "American Society of Blood and Marrow Transplantation" recommend that patients should be routinely revaccinated after transplantation if they are off immunosuppressive therapy and do not suffer from GVHD: beginning of vaccinations with nonliving vaccines in the second year after HSCT, beginning of vaccinations with live attenuated vaccines in the third year after HSCT. Life-long seasonal influenza vaccination is recommended for all HSCT candidates and recipients, beginning during the influenza season before HSCT and resuming > 6 months after HSCT. IT would be appreciated if working groups of these societies could find consensus recommendations on open and controversial questions in the near future.

[Antiinfectious prophylaxis in pediatric oncology. Work group "Quality Assurance" of Society for Pediatric Oncology and Hematology (GPOH)]. / Die antiinfektiöse Prophylaxe in der pädiatrischen Onkologie. Arbeitskreis "Qualitätssicherung" der GPOH.

Infections in disease- and/or chemotherapy-related neutropenia are major, often emergency-type problems in the treatment of pediatric oncology patients and explain the ongoing discussion about antiinfectious prophylaxis. The different aspects of prophylaxis and an overview on the literature are presented. Antiinfectious prophylaxis in pediatric oncology includes the following issues: 1. General aspects such as information for patients and parents on neutropenia and risk of infectious diseases and indication and management of reverse isolation and barrier isolation; 2. antibacterial prophylaxis with oral non-absorbable and oral absorbable antibiotics; 3. Pneumocystis carinii (Pc) prophylaxis; 4. antifungal prophylaxis to prevent disseminated candidiasis and aspergillosis; 5. antiviral prophylaxis, especially varicella-zoster-virus (VZV) post-exposure prophylaxis and cytomegalovirus (CMV) prophylaxis; 6. immunoglobulins and hematopoietic growth-factors (HGF); 7. active immunization. An evaluation of those measures leads to the following conclusions: A major controversy exists regarding antibacterial and antifungal prophylaxis. Probably not effective are the use of reverse isolation and of oral, non-absorbable antibiotics. Oral absorbable antibiotics, antifungal prophylaxis using fluconazole and amphotericin B and the use of hematopoietic growth factors are likely to be effective. Clearly effective are strict hand-washing procedures, Pc and CMV prophylaxis and passive vaccination against VZV in case of VZV exposure of a seronegative patient.

Vancomycin-resistant-enterococci--colonization of 24 patients on a pediatric oncology unit.

BACKGROUND: Colonization with multidrug-resistant vancomycin-resistant-enterococci (VRE) could become a serious problem, since there is no proven therapy in case of an infection or in case of transfer of glycopeptid-resistance to other organisms. PATIENTS: Description of 24 from 48 pediatric oncology patients with VRE-colonization. METHODS: Stool samples were taken from all patients of our pediatric oncology unit from March 1996 until June 1997. Barrier isolation was introduced in May 1996, a prudent use of glycopeptid antibiotica in July 1996. RESULTS: 193 stool sample examinations demonstrated that 24 (50%) of the 48 patients were colonized with VRE. 11 (46%) of these 24 patients were VRE-carriers at the time of their first examination; 9 (37%) patients acquired VRE during their therapy and 4 (17%) patients had come from other hospitals and already were VRE-positive when they entered our unit. In March 1997, one year after the outbreak only four patients still were VRE-positive, in June 1997 all of them were VRE-negative. The average time of colonization was 12.5 weeks. 17 (70%) of the 24 colonized patients had received glycopeptide antibiotics, 16 of them within two months before the appearance of VRE in their stool. Five colonized patients died, four of them because of their oncological illness, one because of a sepsis without proof of VRE in his blood. In the end none of our patients suffered from a VRE-infection, and besides that, the transfer of glycopeptid-resistance to other organisms was not observed. CONCLUSION: With barrier isolation and a very restrictive use of glycopeptid-antibiotica, colonization can be decreased and even stopped. Inspite of the high number of colonized patients no VRE-infectious disease occurred.

[The Munich study on the treatment of acute lymphoblastic leukemia in childhood (ALL 77-02)]. / Münchner Studie zur Behandlung der akuten lymphoblastischen Leukämie im Kindesalter (ALL 77-02).

149 children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved by vincristine, daunorubicine, L-asparaginase and prednisone. During consolidation the patients received three intermediate dose methotrexate (MTX) infusions over 24 hours combined with intrathecal MTX, followed by L-asparaginase. High-risk patients were treated in addition with high dose cyclophosphamide and ARA-C over 3 weeks. Standard risk patients received cranial irradiation with 18 Gy, high-risk patients with 24 Gy. Maintenance therapy was performed with 6-mercaptopurine and MTX orally. Immunologic phaenotyping revealed: c-ALL 73%, pre-T or T-ALL 15%, c/T-ALL 4% and undifferentiated leukemia (AUL) 8%. Only 1 patient was nonresponder, 7 patients died during induction therapy, 5 patients during continuous complete remission (CCR). 18 relapses occurred, 12 of which were systemic, 8 CNS and 2 testicular relapses. In the total group the 54 months probability of CCR is 0,68 +/- 0,05 (life-table-analysis), for the reduced group 0,75 +/- 0,05. In the reduced group the probability of CCR at 54 months for standard risk patients is 0,86 +/- 0,06; for high-risk patients 0,60 +/- 0,09; for patients with c-ALL 0,73 +/- 0,08; for patients with c/T-ALL 1,0 +/- 0,0; for patients with pre-T or T-ALL 0,58 +/- 0,2 and for patients with AUL 0,45 +/- 0,25. For the reduced group the CCR probability at 54 months in relation to the leukocytes (WBC) at diagnosis is in patients with WBC less than 25 X 10(3)/mm3: 0,80 +/- 0,06; for patients with WBC greater than 25 X 10(3)/mm3: 0,63 +/- 0,11.