12th Congress of the European Hematology ... - Haematologica

Infection and supportive care I
0201
COMBINATION ANTIFUNGAL THERAPY WITH ECHINOCANDIN AND POLYENE IN
IMMUNOSUPPRESSED PATIENTS WITH INVASIVE FUNGAL INFECTIONS FAILING FIRST
LINE TREATMENT
L. Pagani, 1 E. Morello, 2 C. Vedovelli, 1 P. Mian, 1 B. Amato, 2 P. Viale3 1 Infectious Diseases Unit, BOLZANO; 2 Bone Marrow Transplantation Unit,
BOLZANO; 3 Udine University, UDINE, Italy
Background. Invasive fungal infections (IFI) are strongly associated to illness
and death in immunosuppressed or high risk patients (pts), especially
in those experiencing failure to primary therapy. Aims. At evaluating
second line combination antifungal therapy (CAT) with echinocandin
and polyene in critically ill pts with IFI. Methods. From November 2003
to April 2005, 18 pts affected by IFI (8 with candidemia due to C. albicans,
3 due to C. glabrata, 2 due to C. krusei, and 5 with pulmonary
aspergillosis), who had failed primary antifungal therapy, were treated
with Caspofungin (CSP) 70 mg on 1st day, and 50 mg thereafter, plus low
dose (LD) AmphotericinB deoxycholate (dAmB) 0.5 mg/kg/d. All pts had
high risk underlying conditions (5 acute myelogenous leukemias, 6 solid
tumors, 5 prolonged intensive care unit (ICU) stays, and 2 major abdominal
surgical interventions). Failure to prior therapy was determined by:
1) fever and worsening of clinical conditions, and 2) persistent candidemia,
or 3) worsening of lung CT scan together with increase of
Aspergillus galactomannan antigenemia (AGA), after 96 hours (hrs) from
the start of antifungal therapy. Results. All 18 pts were clinically unstable
and critically ill, and 13 out of 18 had been admitted to ICU at the time
of switching therapy; 5 patients never required admission to ICU. Within
72-96 hrs from the beginning of CAT, clinical stability and fever clearance,
together with negative blood culture, or negative AGA were
observed, and confirmed thereafter. LD dAmB did not require any premedication,
but none of the pts suffered from side effects, nor treatment
discontinuation was needed. All patients survived. Mean CAT duration
was 26 days, and mean ICU stay was 9 days, before pts transfer to either
medical or surgical wards. None of the pts relapsed within a follow up
period of at least 60 days from the end of treatment. Conclusions. In heavily
immunosuppressed pts, antifungal therapy remain a major challenge.
CAT with echinocandin, such as CSP, and polyene, is an appealing option
supported by promising data. In our experience, this treatment schedule
with CSP and LD dAmB appeared effective in critically ill pts with IFI failing
primary treatment. The synergistic activity of dAmB, even at LD,
plus CSP seems to be clinically relevant; LD dAmB allows not only a lower
incidence of side effects, but also a remarkable cost sparing in comparison
with lipid formulations. Moreover, compared to the available clinical
data in similar situations, both time to clinical stability, and to discharge
from ICU appear shortened in patients under CAT. Wider clinical
studies in these selected settings are needed to clarify the impact on survival
of this salvage treatment schedule.
0202
HIGH INCIDENCE OF INVASIVE FUNGAL SINUSITIS IN PATIENTS UNDERGOING
UNDERGOING INDUCTION THERAPY FOR ACUTE MYELOID LEUKAEMIA OR
MYELODYSPLASIA WITH FLUDARABINE AND CYTARABINE BASED REGIMENS:
A RETROSPECTIVE ANALYSIS
T. Todd, 1 M.W. Besser, 2 E.J. Gudgin, 2 D.A. Enoch, 3 C. Crawley, 4
J.I.O. Craig, 4 M.S. Young Min, 5 J. Cargill, 5 P. Sartori, 1 H.A. Ludlam, 6
G.A. Follows, 1 R.E. Marcus1 1 Addenbrooke's Hospital, CAMBRIDGE; 2 Dept.Haematology, Addenbrooke's
Hospital, CAMBRIDGE; 3 Dept.Microbiology, Addenbrookes Hospital, CAM-
BRIDGE; 4 Dept Haematology, Addenbrooke's Hospital, CAMBRIDGE;
5 Dept.Haematology, West Suffolk Hospital, BURY ST.EDMUNDS, SUF-
FOLK; 6 Addenbrookes Hospital, CAMBRIDGE, United Kingdom
Background. Invasive fungal infections have been relatively well documented
in stem cell transplantation4 (SCT) but not in the setting of
intensive chemotherapy (ICT) alone. Aspergillus species are the commonest
causative organism. Optimal treatment involves systemic antifungal
therapy, combined with surgical debridement 1,6. Reported mortality
is 40-70%5,7 and long term morbidity approaches 70%. Aims. We
evaluated the impact, and differential incidence, of IFS in patients with
de novo, relapsed or refractory acute myeloid leukemia (AML) or
myelodysplasia (MDS) who received either fludarabine plus cytarabine
(FLA) based induction chemotherapy or alternative ICT. Methods. All
12 th Congress of the European Hematology Association
121 patients from 2 centres with a primary diagnosis of AML or MDS
who received ICT between 1 January 2003 and 1st October 2006 were
retrospectively included in the study. Over that time 39/121 patients
received FLA based regimens. Records of hospital maintenance/ construction
activity, climatic data and microbiological surveillance were
also reviewed. IFS was classified according to current EORTC/ BAMSG
criteria. Results. 5 proven, 1 probable and 1 possible cases of IFS were
identified. The latter was excluded due to subsequent identification of
a possible dental abscess. By univariate analysis there was no significant
difference between the FLA and other ICT group in median age, sex,
duration of neutropenia and incidence of positive blood cultures (table
1). The FLA group contained significantly more patients with relapsed/
refractory AML. All patients received prophylactic fluconazole except
during a brief period of minor construction work on one unit when itraconazole
was used. IFS occurred only in the FLA group (Chi2 analysis
p50 days) and 1 had treatment
abandoned. Two of this group died of relapsed haematological disease.
Summary and conclusions. A major change in AML/ MDS remission induction
therapy over the last decade has been the introduction of FLA based
regimen. Recent studies have questioned both their superiority compared
to other regimens especially in view of profound immunosuppression
due to fludarabine. Our study highlights a high incidence of IFS
as a previously unrecognised consequence of FLA chemotherapy in
patients with previously treated or de novo myeloid malignancy.
Table 1. Characteristics of the patient cohorts.
0203
ERYTHROCYTE POPULATIONS WITH CD55 AND/OR CD59 DEFICIENCY IN PATIENTS
WITH HIV INFECTION AND HEMOPHILIA
A. Sarantopoulos, 1 E. Terpos, 2 A. Kouramba, 1 O. Katsarou, 1
J. Stavropoulos, 2 S. Masouridi, 1 J. Meletis, 1 A. Karafoulidou1 1 2 Laikon General Hospital, ATHENS; 251 General Airforce Hospital, ATHENS,
Greece
Background. Anemia is present in almost 35% of patients with HIV
infection. Its pathogenesis is multifactorial and includes chronic inflammation,
anti-viral agents, hemolysis, etc. Myelodysplastic syndrome
(MDS)-like features have also been described in HIV. CD55 and CD59
are complement regulatory proteins that are linked to the cell membrane
via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in
paroxysmal nocturnal hemoglobinuria (PNH) and other hematological
haematologica/the hematology journal | 2007; 92(s1) | 73