A Non-interventional Multicentre Prospective Registry to Monitor the Incidence of Invasive Fungal Infections and to Monitor the Diagnostic and Therapeutic Management of Suspected Fungal-related Febrile Episodes in Patients With Malignant Hemopathies or Subjected to Haematopoietic Cell Transplant for the Treatment of Onco-haematological Diseases (HEMA E-CHART 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
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
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
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
- A multicentre, prospective registry for monitoring invasive fungal infections in
- 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
- 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
- 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
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
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
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.
Observational Model: Cohort, Time Perspective: Prospective
number of febrile events
Italy: Ethics Committee