[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.

Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.

PURPOSE: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. PATIENTS AND METHODS: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. RESULTS: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P

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.

[Improved treatment results in children with AML: Results of study AML-BFM 93]. / Verbesserung der Prognose bei Kindern mit AML: Ergebnisse der Studie AML-BFM 931.

BACKGROUND: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with cytarabine and etoposide. After induction all patients were stratified to the standard or high risk group. To improve outcome in high risk patients high dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the efficacy and toxicity accordingly. PATIENTS AND METHODS: 471 children with de novo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk). RESULTS: Overall, 387 of 471 (82 %) patients achieved remission, 5-year survival, event free survival (EFS), and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 % blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19 % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction reduction after induction occurred in 6 % patients in both arms. In the total group of patients probabilities of five years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin. However, in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome in high risk patients was superior in study 93 compared to study 87 (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %, p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM. CONCLUSION: Compared to study AML-BFM 87 treatment results in study AML 93 improved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.

[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.

MR angiography versus color Doppler sonography in the evaluation of renal vessels and the inferior vena cava in abdominal masses of pediatric patients.

OBJECTIVE: Involvement of renal vessels and the inferior vena cava (IVC) plays a decisive role during operative planning for removal of abdominal masses in pediatric patients. Advantages and limitations of MR angiography and color Doppler sonography for determining these factors were evaluated. MATERIALS AND METHODS: MR angiography and color Doppler sonography were performed preoperatively in 42 neonates, infants, and children with abdominal masses and were compared with spin-echo MR imaging and with surgical findings. Variables evaluated were anatomic variants, vessel displacement, patency of vessels, collateral circulation, and intravascular tumor extension. Quality of vessel visualization was assessed in vessels not affected by tumor. RESULTS: In 88% of unaffected renal vessels, the entire vessel course could be visualized on MR angiography compared with 58% on color Doppler sonography and 43% on spin-echo MR imaging. In four of nine cases, color Doppler sonography revealed an accessory renal artery, whereas MR angiography revealed these variants in seven of nine cases. MR angiography showed 79% and color Doppler sonography 66% of displaced vessels. Unlike MR angiography, color Doppler sonography did not reveal five stenotic renal veins because they could not be completely imaged. In two cases, however, MR angiography falsely indicated an occlusion of the IVC, whereas color Doppler sonography showed residual flow. CONCLUSION: Anatomic variants, vessel displacement, collateral circulation, and neoplastic vessel infiltration were revealed more accurately by MR angiography than by color Doppler sonography. In cases in which patency of the IVC is unclear on MR angiography, color Doppler sonography should also be performed.

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.

Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood--follow up after 9 years. Coall Study Group.

UNLABELLED: A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (each combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year event-free survival (EFS) rate for the whole group is 69% +/- 3%, and the survival rate 75% +/- 3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12% +/- 7% vs. 75% +/- 3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged < 1 year (6/6 relapses) or aged > or = 10 years had a worse prognosis (EFS 64% +/- 5% vs. 77% +/- 4% in patients 1-10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC > or = 100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72% +/- 5% vs. RR 67 +/- 5%). CONCLUSION: The COALL 85/89 treatment protocol with early intensive therapy and rotation of different drug combinations offers longterm disease-free survival for children with high-risk ALL. a continuous 4-week exposure to one drug combination may be necessary to achieve optimal results, especially in children with a high leukaemic cell burden.

[Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study]. / Einfluss von Dosisintensität und therapiebedingter Leukozytopenie in der Intensivtherapie auf die Prognose bei akuter lymphatischer Leukämie im Kindesalter. Untersuchungen bei 213 Patienten der Studie COALL-85. COALL-Studiengruppe.

Dose intensity (DI) plays an important role in the treatment of neoplastic diseases. The individual DI within a protocol may vary considerably and thus may be an important prognostic factor. In 213/305 patients treated in the cooperative study COALL-85 for childhood acute lymphoblastic leukemia the following parameters of individual therapy intensity were analyzed: Total time for intensive treatment, cumulative doses of single drugs, mean relative dose (= relation between received and prescribed doses of all drugs), mean relative dose intensity ( = mean relative dose/time) as well as frequency and duration of leukocytopenia. Therapy for LR (low-risk) and HR (high-risk) patients were separately analyzed by both life-table method and multivariate regression analysis. Neither length of time, mean relative dose intensity nor the other parameters had any significant influence on prognosis within the HR protocol. The only significant prognostic factor was the remission status on day 28 (p less than 0.001 in multivariate analysis). In contrast patients treated with the LR protocol had significantly fewer relapses if treatment resulted in leukocytopenic episodes (probability for event free survival (EFS) = 0.76 in patients with one or two leukocytopenic episodes compared to 0.52 in patients with none). Patients with a mean relative dose greater than 0.9 showed a higher EFS of borderline significance than patients with mean relative dose less than = 0.9 (0.72 vs 0.49, p = 0.09). We would like to conclude, that treatment protocols with very intensive and prolonged combination chemotherapy have a certain margin of safety in DI without disadvantage for the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

[Initial response to therapy as an important prognostic factor in acute lymphoblastic leukemia in childhood. COALL study group]. / Initiales Ansprechen auf die Therapie als wichtigster prognostischer Faktor bei der akuten lymphoblastischen Leukämie im Kindesalter. COALL-Studiengruppe.

Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL-ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS)

[The COALL-85 cooperative study for risk patients with acute lymphatic leukemia: initial results]. / Kooperative Studie COALL-85 für Risikopatienten mit akuter lymphatischer Leukämie: Erste Ergebnisse.

A frequent change of non-crossresistant drug combinations might obviate the problem of multiple resistant cell lines in malignant diseases and thus increase cure rates. In a multicenter cooperative study for childhood acute lymphoblastic leukemia (ALL) 109 high-risk patients were randomized to receive 5-6 different drug combinations either in slow rotation (change of drugs every 4-6 weeks) or in rapid rotation (change of drugs every 2-3 weeks) for early intensive treatment. Both groups received the same total amount of drugs within the same period of time. 108/109 patients achieved complete remission. One child failed to enter remission and one was lost in remission due to viral infection. Patients in the rapid rotation arm required 2-3 weeks less time to complete the intensive therapy due to fewer episodes of prolonged myelosuppression. Toxic side effects and infectious complications were comparable in both groups. 9/109 patients relapsed, 6 in the bone marrow and 3 in the central nervous system. As yet none of the 31 patients with an initial white blood count of greater than or equal to 100/nl has relapsed. The probability of relapse-free survival is 88% in the rapid rotation arm and 86% in the slow rotation arm at 2 1/2 years. The results compare favourably with other protocols for high-risk patients but have still to be considered as preliminary because of the short median observation time of 18 months.

[Active chickenpox vaccination of children with acute leukemia or other neoplastic diseases]. / Aktive Varizellenimpfung bei Kindern mit akuter Leukämie oder anderen neoplastischen Erkrankungen.

26 patients with acute leukemia and other malignancies susceptible to varicella were vaccinated during maintenance chemotherapy. Vaccination was done with OKA strain of live attenuated varicella vaccine developed by Takahashi 1974. All recipients showed no adverse clinical reactions. There was no spread of vaccine virus to others. Seroconversion was 94% in seronegative patients. In those having low antibody titers before vaccination in 56% booster effect was demonstrable. None of the seroconverted recipients contracted varicella in spite of documented contact exposure. Vaccine zoster was not observed. The results suggest that in immunocompromised children live varicella vaccination has a protective effect against varicella infection which has a described mortality rate up 7% in this patients.

[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.