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Purpose: Intensive care unit (ICU) admission of allogeneic hematopoietic stem cell transplant (HSCT) recipients is associated with relatively poor outcome. Since longitudinal data on this topic remains scarce, we analyzed reasons for ICU admission as well as short- and long-term outcome of critically ill HSCT recipients., Methods: A total of 942 consecutive adult patients were transplanted at Hannover Medical School from 2000 to 2013. Of those, 330 patients were at least admitted once to the ICU and included in this retrospective study. To analyze time-dependent improvements, we separately compared patient characteristics as well as reasons and outcome of ICU admission for the periods 2000-2006 and 2007-2013., Results: The main reasons for ICU admission were acute respiratory failure (ARF) in 35%, severe sepsis/septic shock in 23%, and cardiac problems in 18%. ICU admission was clearly associated with shortened survival (p < 0.001), but survival of ICU patients after hospital discharge reached 44% up to 5 years and was comparable to that of non-ICU HSCT patients. When ICU admission periods were compared, patients were older (48 vs. 52 years; p < 0.005) and the percentage of ARF as leading cause for ICU admission decreased from 43% in the first to 30% in the second period. Over time ICU and hospital survival improved from 44 to 60% (p < 0.01) and from 26 to 43% (p < 0.01), respectively. The 1- and 3-year survival rate after ICU admission increased significantly from 14 to 32% and from 11 to 23% (p < 0.01)., Conclusions: Besides ARF and septic shock, cardiac events were especially a major reason for ICU admission. Both short- and long-term survival of critically ill HSCT patients has improved significantly in recent years, and survival of HSCT recipients discharged from hospital is not significantly affected by a former ICU stay.

Cancer registries collect data about the occurrence and temporal changes of the occurrence of all types of cancer. This information is an important basis for health administration as well as for the evaluation of possible cancer causes. Cancer clusters can be detected by analysis of registry data according to place or district of residence of diseased persons. Cancer registries frequently receive enquiries from concerned citizens asking for investigation of the causes of suspected cancer clusters. The management of suspected cancer clusters can be described as crisis management due to the mixing of medical, biological, political, and psychological factors. In this article, we present an overview of current guidelines and methods for handling suspected cancer clusters by cancer registries. Moreover, the numerical analysis of small-scale cancer registry data is illustrated using two examples from the Bavarian Cancer Registry.

Reactivation of viral infections is common in patients with solid tumour or haematological malignancy. Incidence and severity depend on the extent of cellular immunosuppression. Antiviral prophylaxis may be effective to prevent viral reactivation. In 2006, the Infectious Diseases Working Party of German Society for Hematology and Medical Oncology (DGHO) published guidelines for antiviral prophylaxis in these patient populations. Here, we present an update of these guidelines for patients with solid and haematological malignancies undergoing antineoplastic treatment but not allogeneic stem cell transplantation. Relevant literature for reactivation of different viruses (herpes simplex virus (HSV), varicella zoster virus (VZV), hepatitis B virus (HBV) and respiratory viruses) is discussed to provide evidence-based recommendations for clinicians taking care of this patient population. We recommend a risk-adapted approach with (val)acyclovir against HSV and VZV in patients treated with alemtuzumab, bortezomib or purine analogues. Seasonal vaccination against influenza is recommended for all patients with solid or haematological malignancies regardless of antineoplastic therapy. Hepatitis B screening is recommended in lymphoproliferative disorders, acute leukaemia, and breast cancer, and during treatment with monoclonal anti-B-cell antibodies, anthracyclines, steroids and in autologous stem cell transplantation. In those with a history of hepatitis B prophylactic lamivudine, entecavir or nucleotide analogues as adefovir are recommended to prevent reactivation.

Purpose: The aim of this sequential mixed methods study was to develop a PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events)-based measure of the symptom experience of late effects in German speaking long-term survivors of allogeneic stem cell transplantation (SCT), and to examine its content validity., Methods: The US National Cancer Institute's PRO-CTAE item library was translated into German and linguistically validated. PRO-CTCAE symptoms prevalent in ≥50% of survivors (n = 15) and recognized in its importance by SCT experts (n = 9) were identified. Additional concepts relevant to the symptom experience and its consequences were elicited. Content validity of the PROVIVO (Patient-Reported Outcomes of long-term survivors after allogeneic SCT) instrument was assessed through an additional round of cognitive debriefing in 15 patients, and item and scale content validity indices by 9 experts., Results: PROVIVO is comprised of a total of 49 items capturing the experience of physical, emotional and cognitive symptoms. To improve the instrument's utility for clinical decision-making, questions soliciting limitations in activities of daily living, frequent infections, and overall well-being were added. Cognitive debriefings demonstrated that items were well understood and relevant to the SCT survivor experience. Scale Content Validity Index (CVI) (0.94) and item CVI (median = 1; range 0.75-1) were very high., Conclusions: Qualitative and quantitative data provide preliminary evidence supporting the content validity of PROVIVO and identify a PRO-CTCAE item bundle for use in SCT survivors. A study to evaluate the measurement properties of PROVIVO and to examine its capacity to improve survivorship care planning is underway., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Patients with prolonged neutropenia or immunosuppression after stem cell transplantation are at a high risk of developing invasive fungal infections. Antimycotic prophylaxis is used to reduce the associated morbidity and mortality. The following classes of antimycotic agents are currently available: azoles (e.g., fluconazole, itraconazole, posaconazole), echinocandins (caspofungin, micafungin), and amphotericin B.

Stem cell transplantation in pediatric patients with leukemia has been a matter of debate since the first successful transplantation in a child with aplastic anemia in Germany in 1975. Since then, there has been a long way to implement fully stem cell transplantation strategies into the treatment studies organized within BFM Groups for first line or second line treatment of acute and chronic leukemias and myelodysplastic syndrome. The role of different risk groups, different donors, stem cell sources and alternative approaches as haploidentical transplantation as well have been studied as the impact of chimerism and minimal residual disease. Finally, for all leukemias and myelodysplastic syndromes integrated treatment pathways have been developed, which integrate stem cell transplantation on an evidence base into the treatment of the patient., (© Georg Thieme Verlag KG Stuttgart · New York.)

To assess the level of graduation, the wish to have children and the course of pregnancy among former patients with childhood leukemia in comparison to the general German population and depending on gender, a nationwide survey was conducted in 2008. In total 63.6% (1476/2319) of the contacted survivors of childhood leukemia participated (mean age 25.7 years, range 19-43 years). Survivors graduated at higher levels of school compared to the general population, with 48.6% (female) versus 38.0% and 52.6% (male) versus 35.8% (p < 0.001). Also, 93.3% of female and 89.3% of male survivors indicated a similar general wish to have children compared to the general population. Survivors reported parenthood less frequently compared to the general population (p < 0.001). The course of pregnancy in survivors was characterized by fewer abortions (p < 0.001). Having leukemia in childhood and adolescence impairs the likelihood of becoming a parent but reduces neither the wish to have children nor the level of graduation.

Background: With improved cure rates of cancer in children and adolescents, the long-term effects of oncological treatment, including impaired fertility, have become an important clinical issue., Methods: In 2008, we conducted a nationwide survey in Germany in which we asked 4689 female and male patients who had been treated for cancer in childhood or adolescence for information on menstruation, previous fertility testing (if any), attempts to conceive, and pregnancies. In a complementary study carried out in 2009, 748 former cancer patients in Berlin were offered hormone testing and sperm analysis. The defined criteria for suspected infertility were, in women, anti-muellerian hormone levels below 0.1 ng/mL; in men, FSH levels above 10 IU/L and inhibin B levels below 80 pg/mL, or azoospermia., Results: The respondents to the nationwide survey included 1476 leukemia survivors and 1278 persons who had had a solid tumor. 104 former leukemia patients and 96 former solid tumor patients had already undergone fertility testing, leading to the suspicion of infertility in 26% and 34% of the persons in these respective groups (95% confidence intervals [CI], 18%-34% and 25%-43%). The patients who were tested in the Berlin study included 59 leukemia survivors and 104 persons who had had a solid tumor. The frequency of suspected infertility in these two groups was 25% and 27%, respectively (95% CI, 14%-36% and 18%-36%)., Conclusion: Up to one-third of adults who undergo fertility testing after having been treated for cancer in childhood or adolescence have suspected infertility. Patients and their parents should be counseled about the possibility of infertility and about fertility-preserving measures.

During the past 25 years a highly effective infrastructure for clinical trials was developed in hematology. Following initial funding by the BMFT (Ministry for Research and Technology) a number of large multicenter study groups for leukemia and lymphoma were developed. Treatment results from these studies often represent the"gold standard". However, since no standard therapy is defined for these diseases, the study groups aim to treat all patients within treatment optimization trials (TOT) to combine research and care. They contribute considerably to quality control in therapy and diagnostics, e.g., by establishing central reference laboratories. The regulatory requirements for clinical trials were extended considerably after the activation of the 12th drug law and TOTs now have to fulfill requirements similar to registration trials in the pharmaceutical industry. Due to the considerable bureaucratic effort and increased costs, only few large multicenter trials could thereafter be initiated and a substantial disadvantage for independent academic research becomes clearly evident.

Background: Leukemias are a challenge and a cost factor to society because of their frequency in all age groups. They also serve as a model for a variety of diseases and possess exemplary relevance for basic research and patient care. Leukemia research and therapy have achieved high standards and even a leading position in Germany with regard to clinical trials, standardization of diagnostics and molecular studies of prognostic factors, signal transduction and gene expression. Progress is hampered, however, by fragmentation of leukemia trial groups, diagnostic approaches and treatment research activities., Goals: A network was therefore created to integrate the leading leukemia trial groups on chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphatic leukemia (ALL), myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (CMPD) and their interdisciplinary partners (diagnostics, treatment research, biometry) in cooperation with basic research and pharmaceutical industry to foster advancements in leukemiarelated research and health care through clinical trials, promotion of translational research, introduction of standards for diagnostics and therapy, and development of evidence-based guidelines., Achievements: Achievements include establishment of central information, communication and management structures, creation of an AML intergroup comprising five study groups, formation of an MDS study group and establishment of platforms for diagnostics, genomics and proteomics, and medical informatics. Exchange of scientific progress is mediated by intra- and internet, biannual newsletters, regular project group meetings, and annual network symposia., Perspectives: On the basis of experience with the Competence Network "Acute and chronic leukemias" with its management, communication and information structures, the "European LeukemiaNet" (ELN) has been established within the 6th Framework Program of the European Union. The ELN integrates 78 leading leukemia trial groups (AML, ALL, CML, CLL, MDS, and CMPD), their 83 interdisciplinary partner groups (diagnostics, treatment research, registry, guidelines), industry and SMEs (small- and medium-sized enterprises) across Europe to form a cooperative network for advancements in leukemia-related research and health care.

Objectives: Aim of this study was to analyze the feasibility of oncological treatment in pediatric patients belonging to Jehovah's Witnesses and to describe the changing policy in performing transfusions and supportive care measures at two German pediatric cancer institutions., Patients and Methods: Over a period of 16 years 21 treatments according to the current cooperative protocols were performed in 14 children of Jehovah's Witnesses. Various hematological supportive care measures such as supplementation with iron, human erythropoietin, interleukin 11, granulocyte colony-stimulating factor and autologous or allogeneic stem cell rescue had been applied. For comparison matched pairs treated in our hospitals not belonging to Jehovah's Witnesses and 50 pediatric and adult oncological patients belonging to Jehovah's Witnesses reviewed from the international literature were analyzed with respect to transfusions and outcome., Results: So far, 9 of 14 children are surviving 16-195 months (median 26 months). During the primary therapy they received markedly less transfusions than the control cohort (-39,1% red blood cell transfusions and -37,5% platelet transfusions). The review of 50 reported cases showed that oncological therapy can also be successfully performed with a restricted transfusion regimen in children and particularly in adults., Conclusion: Pediatric cancer patients belonging to Jehovah's Witnesses can be treated similarly to other patients. A restrictive transfusion policy and the broad application of hematopoietic supportive care measures may reduce transfusions. This treatment policy and a continuous collaboration with the Hospital Liaison Committee for Jehovah's Witnesses appears to create an oncological treatment situation with a high compliance of patients and parents where court orders may not be necessary., (Copyright 2004 S. Karger GmbH, Freiburg)

Goal of the network is the construction of an exemplary cooperative leukemia network for the improvement of medical care and of health related research in acute and chronic leukemias. This is achieved by improved mechanisms of cooperation among all major groups in Germany that deal with the leukemias in research and in patient care. In practice, cooperation between clinical groups and scientists in research institutes is mediated by various instruments that improve communication, flow of information and interdisciplinary cooperation and also increase information transfer from top research institutions to clinical translation. The network comprises more than 1400 participants in about 400 university centers, large community hospitals and specialty practices with functional communication structures, interdisciplinary cooperation and nation-wide logistics. The improved cooperation and the accelerated information transfer from the bench to the "bedside" results in an added value that ultimately results in improved survival results of patients and in superior competitiveness of involved research workers and clinicians. Sustainability is addressed by establishing a leukemia foundation to support long term financial coverage of the network and by negotiating a proposal for a European Network of Excellence against leukemia within the Sixth Framework Programme of the European Union.

Background: As a result of improved therapeutic and diagnostic modalities the survival rate of children with neoplastic disease has increased dramatically. The consequences of these scientific advances have led to increased malignancy-related critical complications requiring the expertise of intensive care practitioners., Patients: From all children admitted to the pediatric intensive care unit (PICU) of the Martin-Luther University Halle those with hematologic-oncologic condition were evaluated., Results: From 4068 PICU admissions 196 (4.8%) oncologic patients were identified. Most of them were admitted for postoperative care, monitoring or intervention. 24 patients were admitted because of severe disease or treatment related complications. 14 out of 24 (58%) patients died on PICU. Mortality was significant higher in a subgroup requiring mechanical ventilation or suffering from sepsis. All patients but two with multi-organ system failure (> or = 2 organs) died., Conclusions: Children with neoplastic disease can benefit from pediatric intensive care unit (PICU) support. Successful treatment of life-threatening complications requires a close cooperation of pediatric oncology and PICU. Further studies are necessary to improve therapeutic strategies in oncology patients requiring PICU admission.

Background: The prognosis for patients with childhood leukemia has improved steadily over the last decades due to major progress in therapy. Much of this progress remains unaccounted for in traditional estimates of long-term survival rates, which essentially reflect the survival experience of patients who were diagnosed many years ago., Methods: The authors applied a new method of survival analysis, called period analysis, to provide up-to-date estimates of long-term survival rates. The analysis is based on data from the nationwide German Childhood Cancer Registry and includes 8059 children who were diagnosed with leukemia between 1981 and 1998. The most up-to-date 5-year, 10-year, and 15-year survival estimates were obtained by period analysis and were compared with to the most up-to-date survival estimates from traditional methods of survival analysis., Results: Period estimates (95% confidence intervals) of 5-year, 10-year, and 15-year survival rates achieved by 1998 were 81% (79-83%), 77% (74-79%), and 73% (70-76%), respectively, for all patients with leukemia combined; 86% (84-88%), 81% (79-84%), and 77% (74-81%), respectively, for patients with acute lymphocytic leukemia; and 59% (53-65%), 59% (53-65%), and 57% (49-64%), respectively, for patients with acute nonlymphocytic leukemia. Substantially lower estimates would have been obtained with traditional methods of survival analysis., Conclusions: These results from one of the world's largest childhood cancer registries reveal that cure rates of childhood leukemia achieved by the end of the second millennium are higher than suggested by previous estimates based on traditional methods of survival analysis., (Copyright 2001 American Cancer Society.)

Taking as an example the special research programme ('Sonderforschungsbereich') in leukemia research and immunogenetics (SFB120) of the University of Tübingen, we intend to discuss how research subsystems should be built up, which functions they should take over and which network architecture is suitable. Furthermore, we examined to what extent research subsystems can be integrated in the computer-supported part of hospital information systems. It can easily be seen that no general solution exists for the structuring. The structure depends rather upon the specific problems and information requirements of individual research units. The clinical environment must be taken into account if research subsystems are to be integrated into the computer-supported part of a hospital information system. Especially in regard to the data protection aspect, we must keep in mind that the connection between subsystems must not necessarily result in the setup of a network for the corresponding computer systems.