A Prospective Registry for Febrile Events in Patients With Malignant Hemopathies or Subjected to Haematopoietic Stem Cell Transplant
A Prospective Registry for Febrile Events in Patients With Malignant Hemopathies or Subjected to Haematopoietic Stem Cell Transplant
Hema e-chart is an electronic case record that can be changed in real time and is based on
 the chronological organisation of the infective events and the therapies prescribed. It
 allows the collection of all personal, epidemiological, diagnostic and therapeutic data
 pertaining to the patient, processing it and analysing the results.

 Aims and objectives of the project

 The aims of this registry are:

 -  To assess how many suspected fungal-related febrile episodes identify an infective
 fungal agent

 -  To have a clear view of the diagnostic and therapeutic actions in the management of
 onco-haematological patients with suspected fungal-related febrile episodes

 -  To assess the impact of anti-fungal therapy on the timing of chemotherapy and transplant
 planning

 -  Perform drug-epidemiology relationship analyses, observe toxicity and interactions with
 antifungal therapies by means of the creation of a national database of fungal
 infections in patients affected by malignant haemopathies

 Design

 -  A multicentre, prospective registry for monitoring invasive fungal infections in
 onco-haematological patients

 -  Registration criteria: patients with newly diagnosed malignant haematological diseases
 (acute and chronic myeloid and lymphoid leukaemia, multiple myeloma, non-Hodgkin's and
 Hodgkin's lymphoma, aplastic anaemia, myelodysplastic syndromes), or patients who, as a
 result of onco-haematological pathologies, have undergone allogenic or autologous
 haematopoietic cell transplants, and have ongoing febrile episodes . The recording of
 consecutive febrile events is required

 -  Data collection for each individual patient will be performed according to the method
 shown in the enclosed flow chart. In the case of a new episode for an existing patient,
 said new episode will be recorded in the same case record as a new event. All collected
 data will be coded into the database

 -  Information relating to about 500 suspected fungal-related febrile events requiring
 antifungal therapy is expected to be collected from approximately 60 centres over the
 course of 18 months

 -  Data collection for each event may be performed following the provision of written
 informed consent, which will be obtained from each patient participating in this health
 survey

 -  The data collected will be handled and stored in full compliance with the Italian laws
 governing privacy

 -  Hema e-chart is a non-interventional registry
Introduction Problems with infections in onco-haematological patients have assumed ever
 increasing importance over recent years, with relation to the development of management
 principles of the various clinical entities. Indeed, infections are primarily correlated with
 reduced immunocompetence (both cellular and humoral immunity) following both intensive
 chemotherapy and the use of immunosuppressant drugs during allotransplantation procedures.
 Furthermore, the common haematological disorders (i.e. acute or chronic myeloid and lymphoid
 leukaemia, lymphoma, myeloma etc) and the treatments required for such diseases contribute
 towards mediating and modulating the risk of infection. Among the various pathogens
 responsible for infections in onco-haematological patients, fungi still represent a problem
 for diagnosis and, despite the current therapeutic options, contribute significantly towards
 transplant-related mortality. The various candidaemias account for 30-40% of deaths, invasive
 aspergillosis for 50-60%, and 75% of deaths are accounted for by infections caused by
 zygomycetes.

 Fungal agents include both the yeasts (e.g. Candida) and the moulds (e.g. Aspergillus,
 Zygomycetes); however over recent years, a different epidemiological trend has been observed
 between the aforementioned macro-categories of etiological agents: while there has been a
 progressive reduction in the epidemiological and clinical burden caused by Candida spp
 infections, the opposite trend has been observed for those caused by moulds, Aspergillus spp.
 and so on. Nevertheless, all clinicians are well aware of this epidemiological development
 the variables associated with risk and the real incidence of fungal infections in patients
 with malignant haemopathies and/or subjected to transplant are not entirely known. A recent
 multicentre retrospective study by the GIMEMA group assessed mould infections in patients
 with malignant haemopathies over a 10 year period. This study showed that 6-7% of patients
 with acute leukaemia can develop a mould infection during one of the various stages of the
 disease (onset of remission, relapse, rescue therapy, etc). Despite the undoubted use of this
 data as a first assessment of the magnitude of the problem, a more thorough epidemiological
 investigation appears in need, above all within the context of being able to plan the correct
 decisional procedure in relation to treatment, independently from the documentation of the
 infection. Secondly, an analysis of the different diagnostic approaches of the individual
 specialists, in terms of disease definitions and diagnostic work-up just as with their
 therapeutic choices, can contribute towards overcoming the high level of managerial
 empiricism still widespread within this medical sector.

 The information which can be gathered from a study of this nature can prove useful for
 deducing the correct diagnostic approach and a suitable therapeutic decision, in day to day
 clinical practice. Hence, an integrated, computerised system, capable of recording the
 various different aspects, can certainly be of help to the haematology specialist.

 Aims and objectives of the project

 The aims of this registry are:

 1. to assess how many suspected fungal-related febrile episodes identify an infective
 fungal agent.

 2. to have a clear view of the diagnostic and therapeutic actions in the management of
 onco-haematological patients with suspected fungal-related febrile episodes.

 3. to assess the impact of anti-fungal therapy on the timing of chemotherapy and transplant
 planning

 4. perform drug-epidemiology relationship analyses, observe toxicity and interactions with
 antifungal therapies by means of the creation of a national database of fungal
 infections in patients affected by malignant haemopathies

 Design

 -  A multicentre, prospective registry for monitoring invasive fungal infections in
 onco-haematological patients

 -  Registration criteria: patients with newly diagnosed malignant haematological diseases
 (acute and chronic myeloid and lymphoid leukaemia, multiple myeloma, non-Hodgkin's and
 Hodgkin's lymphoma, aplastic anaemia, myelodysplastic syndromes), or patients who, as a
 result of onco-haematological pathologies, have undergone allogenic or autologous
 haematopoietic cell transplants, and have ongoing febrile episodes . The recording of
 consecutive febrile events is required.

 -  Data collection for each individual patient will be performed according to the method
 shown in the enclosed flow chart. In the case of a new episode for an existing patient,
 said new episode will be recorded in the same case record as a new event. All collected
 data will be coded into the database.

 -  Information relating to approximately 500 suspected fungal-related febrile events
 requiring antifungal therapy is expected to be collected from approximately 60 centres
 over the course of 18 months.

 -  Data collection for each event may be performed following the provision of written
 informed consent, which will be obtained from each patient participating in this health
 survey.

 -  The data collected will be handled and stored in full compliance with the Italian laws
 governing privacy.

 -  Hema e-chart is a non-interventional registry.

 The inclusion of patients in any given therapeutic strategy is not decided in advance, but
 falls within normal clinical practice, and the decision to prescribe any medication is
 entirely independent from that of including the patient in the health survey.

 • Prior to its application, the plan will be submitted to the Ethics Committees of the
 various participating centres.

 Data registration Hema e-chart is an electronic case record that can be changed in real time
 and is based on the chronological organisation of the infective events and the therapies
 prescribed. It allows the collection of all personal, epidemiological, diagnostic and
 therapeutic data pertaining to the patient, processing it and analysing the results. (see
 appendix).

 This case record is located on a site with access controlled by user ID and Password Data
 registration will take place according to the method shown in the enclosed flow-chart

 APPENDIX Hema e-chart Software The Hema e-chart software has been designed to be used in
 multiple specialised health centres. A configuration function allows automatic recognition of
 the centre to which the user submitting their access credentials belongs.

 The data is structured according to the following general outline:

 The patents basic personal data Description of the basic pathology Clinical parameters
 (neutrophils, temperature, etc) Disease type Type of treatment (1st line, 2nd line etc.)
 Drugs used Antibiotics Antivirals Antineoplastics Corticosteroids Immunomodulators Cytokines
 Renal function (calculated automatically as a function of creatinine levels) Hepatic function
 Diagnosis of fungal infection Chemical factors Microbiological factors Invasive tests Name of
 the fungal agent identified Site of infection Antifungal prophylaxis Antifungal agent
 selected Dosage Mode of administration Antifungal therapy Antifungal agent selected Dosage
 Mode of administration Outcome Outcome of the treatment

 -  Complete response (complete resolution of signs and symptoms, normalisation of any
 instrumental and/or mycological tests)

 -  Partial response (significant clinical improvement in both signs and symptoms and in any
 instrumental and/or mycological tests).

 Physician's evaluation of the treatment Investigators comments Tolerability of the antifungal
 therapy Safety of the antifungal therapy Monitoring of any drug interactions

 The Hema e-chart structure allows all the data contained in the case record to be altered and
 saved up to three times per day, while maintaining a complete history of all changes made.
 This way it is possible to follow the patient's progress, the treatments performed, the
 clinical tests requested, in detail, and then be able to assess any correlations existing
 between the actions undertaken and the effects obtained.

 For this reason, the software is supplied with various graphical tools for easier evaluation
 of the data.

 The same patient may be recorded several times in the study, if they incur several febrile
 events within the time period. Data registration allows use of the same personal details so
 as to aid consultation of the data.
Inclusion Criteria:

 -  patients with newly diagnosed malignant haematological diseases (acute and chronic
 myeloid and lymphoid leukaemia, multiple myeloma, non-Hodgkin's and Hodgkin's
 lymphoma, aplastic anaemia, myelodysplastic syndromes), or patients who, as a result
 of onco-haematological pathologies, have undergone allogenic or autologous
 haematopoietic cell transplants, and have ongoing febrile episodes