Primary intestinal aspergillosis after high-dose chemotherapy and autologous stem cell rescue.

Primary invasive aspergillosis of the gut is a rare event and is associated with high mortality. We report for the first time on a patient who had isolated aspergillosis of the small bowel after autologous stem cell transplantation. Diagnosis of invasive aspergillosis of the gut was based on abdominal pain, galactomannan antigenemia and isolation of Aspergillus fumigatus from the stool and was later confirmed by pathohistologic examination.

Diagnostic approaches for immunocompromised paediatric patients with pulmonary infiltrates.

Pulmonary infiltrates in immunocompromised children often pose problems in terms of deciding on further diagnostic and therapeutic procedures, but few studies have evaluated the value of non-invasive and invasive diagnostic methods in paediatric populations. Both galactomannan ELISA and PCR protocols appear to be less useful in children than in adults. Invasive procedures, such as bronchoalveolar lavage or lung biopsy, can yield a pathohistological diagnosis and/or the isolation of a pathogen.

Quantification of chimerism within peripheral blood, bone marrow and purified leukocyte subsets: comparison of singleplex and multiplex PCR amplification of short tandem repeat (STR) loci.

Objective And Methods: Chimerism analysis has become a routine diagnostic procedure after haematopoietic allogeneic stem cell transplantation for early detection of relapse of disease or graft failure. Whereas some centres developed individual in-house short tandem repeat (STR) systems, others prefer commercial multiplex PCR systems. However, little is known about inter-assay variation, which could have a significant impact on treatment decision.

Treatment with caspofungin in immunocompromised paediatric patients: a multicentre survey.

Objectives: Although a paediatric dosage has not been established, caspofungin is occasionally used in paediatric patients. We conducted a multicentre retrospective survey to obtain data on immunocompromised paediatric patients considered to require caspofungin therapy.

Methods: The survey identified 64 patients (median age: 11.

Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus.

Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation (SCT). Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-gamma secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus.

[Diagnostic procedures and management of Fever in pediatric cancer patients].

The rapid institution of empirical broad-spectrum antibiotics has become the gold standard of treatment for febrile neutropenic children undergoing therapy for cancer. With this approach, morbidity and mortality have dropped significantly but have not been eliminated altogether. In recent randomized studies evaluating different drug combinations, there is still a 3-10 % mortality reported in febrile, neutropenic cancer events.

[Infectious complications in pediatric cancer patients].

Infectious complications are still a major cause of morbidity and mortality in pediatric patients undergoing therapy for malignancy. Therapy-induced neutropenia is the most important risk factor for infectious risk in pediatric patients with cancer, but other factors, such as alterations in skin/mucosal barriers, and defects in cell-mediated or humoral immunity also contribute to the risk for infection. In most centers, about two thirds of bacteremic isolates are gram-positive pathogens, whereas gram-negative organisms are isolated less frequently, but are associated with considerably higher mortality rates.

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia.

Infectious complications represent a substantial cause of morbidity and mortality in children undergoing therapy for acute myeloid leukemia (AML). Since it has been shown that alterations in innate immune pathways contribute to the risk for serious infections, we analyzed well-characterized variants in innate immune genes (TNF, IL6, IL8, MPO, CHIT, FCGR2A, TLR2, and TLR4) to determine their possible contribution to infectious complications during therapy for pediatric AML. The study population consisted of 168 North European Caucasian children enrolled on the clinical trial AML-BFM 93.

New antifungal drugs and the pediatric cancer patient: current status of clinical development.

Invasive mycoses are important causes for treatment related morbidity and mortality in severely immunocompromised pediatric patients with hematological malignancies or hematopoietic stem cell transplantation. The past decade has witnessed a major expansion of antifungal drug research, which has resulted in the development of the novel class of echinocandin lipopeptides (anidulafungin, micafungin, caspofungin) and a new generation of antifungal triazoles with improved pharmacological properties (posaconazole, ravuconazole, voriconazole). Whereas caspofungin and voriconazole have been licensed in the European Union, the United States, Canada and several other countries throughout the world, posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory review or in advanced stages of clinical development.

Pheochromocytoma in childhood: implication for further diagnostic procedures.

Unlabelled: We report on our experience with two patients with pheochromocytoma. One patient underwent surgery of pheochromocytoma at the age of 30 y; 18 y later, medullary thyroid carcinoma (MTC) was detected in his son. Subsequently, multiple endocrine neoplasia (MEN) type 2A was diagnosed by genetic examination in both father and son.

Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98.

Purpose: The rates of early death (ED) and treatment-related mortality (TRM) are unacceptably high in children undergoing intensive chemotherapy for acute myeloid leukemia (AML). Better strategies of supportive care might help to improve overall survival in these children.

Patients And Methods: In a retrospective study, we analyzed incidence, clinical features, and risk factors for lethal complications of 901 children enrolled onto the multicenter trials Acute Myeloid Leukemia-Berlin-Frankfurt-Muenster (AML-BFM) 93 and AML-BFM 98.

Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93.

Infections still remain a major cause of therapy-associated morbidity and mortality in children with acute myeloid leukemia (AML). To improve supportive care measurements, detailed information on frequency and characteristic features of infectious complications is needed. We retrospectively analyzed the medical charts of 304 children, treated in 30 hospitals according to the multi-institutional clinical trial AML-BFM 93.

Mediastinal T-cell lymphoma in a boy 7 years after treatment of supratentorial primitive neuroectodermal tumor.

Medulloblastoma/primitive neuroectodermal tumor (PNET) is one of the most common central nervous system tumors in children and requires aggressive multimodality therapy. The authors describe a patient who developed mediastinal T-cell lymphoma 7 years after treatment of supratentorial PNET. Despite a good tumor response, the patient died during induction therapy because of invasive pulmonary aspergillosis.

Combination therapy with caspofungin and liposomal amphotericin B for invasive aspergillosis.

Ina 24-month-old girl with acute lymphoblastic leukemia and invasive aspergillosis, only combination therapy with liposomal amphotericin B and caspofungin achieved a good response. Combination therapy could be a useful treatment option in children with invasive fungal disease, but before it can be routinely recommended, carefully controlled in vivo studies and well-designed randomized clinical trials are needed.

[Analysis of causes of death during intensive chemotherapy according to treatment protocol AML-BFM 93].

Background: During intensive chemotherapy for AML, more than 10% of patients die because of treatment complications but not because of progression of their underlying disease. In order to improve supportive care and to decrease mortality, we analysed the causes of death and their relationship to the cycles of chemotherapy in children undergoing treatment for AML according to the study AML-BFM 93.

Results: Thirty-five (7.

B-Cell lymphoproliferative disorder not associated with Epstein-Barr Virus in a child with relapsed acute lymphoblastic leukemia.

Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein-Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL).

A second look at anorectal infections in cancer patients in a large cancer institute: the success of early intervention with antibiotics and surgery.

Background: Infection of anorectal region represents a significant complication of anti-cancer therapy. Anorectal infection occurs in patients receiving aggressive chemotherapy. Untreated infection leads to substantial morbidity and in the past, mortality.

Short courses of intravenous empirical antibiotic treatment in selected febrile neutropenic children with cancer.

Background: Since the optimal duration of antibiotic therapy in febrile neutropenic patients is not clear, we evaluated the safety and efficacy of short courses of intravenous antibiotic treatment in selected pediatric cancer patients admitted for fever and neutropenia.

Patients And Methods: We retrospectively analyzed the clinical course of children with chemotherapy-induced neutropenia and fever. All patients were treated with empirical intravenous antibiotics.

[Hematopoietic growth factors in prevention and therapy of infectious complications in premature and newborn infants].

Bacterial sepsis continues to be an important cause of morbidity and mortality in neonates. Neutropenia in the newborn, as a result of decreased bone marrow neutrophil storage pool reserves and myeloid committed progenitor cells, increases the risk of sepsis and is associated with a poor prognosis. The hematopoietic colony-stimulating factors G-CSF (granulocyte colony stimulating factor) and GM-CSF (granulocyte-macrophage colony stimulating factor) increase the number of circulating neutrophil number by stimulating neutrophil precursors proliferation.

[Intravenous immunoglobulins in the prevention of infection in children with hematologic-oncologic diseases].

Treatment with intensive myelosuppressive therapy results in decreased levels of immunoglobulins. Whereas pediatric cancer patients undergoing chemotherapy do not benefit from the routine administration of intravenous immunoglobulins, prophylactic intravenous immunoglobulins given after bone marrow transplantation or after peripheral stem cell transplantation reduce infectious complications. Still, prospective clinical trials are needed to define specific treatment groups who can benefit from immunoglobulin support.

[Hematopoietic growth factors in the prevention of infections complications in children with hematologic-oncologic diseases].

The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors.

[Hematopoietic growth factors in prophylaxis and therapy of infections complications in children with neutropenia].

Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the corpus of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors.