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

inding lectin (MBL) gene by polymerase chain reaction with sequencespecific
primers. J Immunol Methods 2000; 241:33-42.
2 Molle I, Peterslund NA, Thiel S, Steffensen R. MBL2 polymorphism and
risk of severe infections in multiple myeloma patients receiving high-dose
melphalan and autologous stem cell transplantation. Bone Marrow
Transplant 2006; 38:555-60.
3 Neth O, Hann I, Turner MW, Klein NJ. Deficiency of mannose-binding
lectin and burden of infection in children with malignancy: a prospective
study. Lancet 2001; 358:614-8.
4 Gordon AC, Waheed U, Hansen TK, Hitman GA, Garrard CS, Turner
MW et al. Mannose-binding lectin polymorphisms in severe sepsis: relationship
to levels, incidence, and outcome. Shock 2006; 25:88-93.
5 Bergmann OJ, Christiansen M, Laursen I, Bang P, Hansen NE, Ellegaard
J et al. Low levels of mannose-binding lectin do not affect occurrence of
severe infections or duration of fever in acute myeloid leukaemia during
remission induction therapy. Eur J Haematol 2003; 70:91-7.
6 Petersen KA, Matthiesen F, Agger T, Kongerslev L, Thiel S, Cornelissen
K et al. Phase I safety, tolerability, and pharmacokinetic study of recombinant
human mannan-binding lectin. J Clin Immunol 2006; 26:465-75.
0614
PREDOMINANCE OF GRAM-NEGATIVE BACTEREMIA IN FEBRILE NEUTROPENIA
EPISODES: AN EPIDEMIOLOGIC EVALUATION IN A BRAZILIAN HEMATOLOGIC SERVICE
L.C. Palma, M.I.A. Madeira, L.F. Dalmazzo, M.C. Favarin, C.E.E.
Velano, C.H. Kruzich, L.C.O. Oliveira, L.L.P. Figueiredo, G.G. Gaspar,
J.F.C. Figueiredo, B.P. Simões, E.M. Rego
HCFMRP-USP, RIBEIRÃO PRETO, Brazil
Background. Some studies have shown a predominance of gram-positive
bacteremia in febrile neutropenia patients. Potential reasons include
the use of indwelling catheters, local environmental conditions and the
administration of specific antibiotic agents, especially prophylaxis. Some
reports have shown that weather’s characteristics could influence the
patterns of infection. Brazilian weather is very heterogeneous varying a
lot along its vast territory. Therefore, there is no consistent data about
Brazilian febrile neutropenia’s epidemiology. Methods. We retrospectively
analyzed a total of 92 patients, which were divided in two groups:
myeloid neoplasia (69 patients) and lymphoid neoplasia (23 patients).
Results. Between 2000-2006, we analyzed 266 febrile neutropenia
episodes. The median age of the patients was 37.5 (16-81) years-old. In
36% of cases, there was at least one organism (bacteria or fungal) isolated
in blood culture. Gram-negative bacteremia was identificated in 65%
of these cases and the most frequent gram-negative bacterias were
Escherichia coli (31%) and Klebsiella pneumoniae (23%). The resistance
of these two bacterias to cefepime, which is the standard empirical treatment
in our service, was 13% and 81%, respectively. Gram-positive bacterias
and fungal were isolated in blood cultures in 31% and 14% of cases,
respectively. Staphylococcus epidermidis was the most frequent
gram-positive bacteria (9%). In 8% of cases, more than one organism
were isolated and gram-negative bacterias predominated in these
episodes (81%). There was in 62% of episodes the presence of at least
one identifiable site of infection. Pneumonia and skin infection were the
most common site of infection (31% and 24%, respectively). There was
no difference in the frequency or resistance of the organisms between
the myeloid and lymphoid neoplasia groups. 15% of patients died during
the febrile neutropenia episode. The most important factors influencing
the overall survival in an univariate analysis were diagnosis of a
myeloid neoplasia (OR:5.86, p=0.0002), bacteremia by Klebsiella pneumoniae
(OR: 4.40, p=0.012), the presence of pneumonia (OR: 4.37,
p=0.0001), age ≥ 65 years-old (OR: 3.6, p=0.015), the presence of a gramnegative
bacteremia (OR: 2.27, p=0.04), the presence of at least one identifiable
site of infection (OR: 2.23, p=0.049). Conclusions. These results differ
from other ones coming from developed countries (Kanamuru and
Tatsumi CID 2004, Ramphal CID 2004), where the gram-positive bacterias
are more frequently isolated in blood culture during febrile neutropenia
episodes. One explanation for our findings is the fact that we
do not usually use ciprofloxacin as a primary prophylaxis. However,
recently, some studies showed a shift towards gram-negative bacteremia
during febrile neutropenia (Guven Support Care Cancer 2006). Therefore,
our results reinforce the concept that antibiotic therapy for febrile
neutropenia should be adapted to the local epidemiologic data.
12 th Congress of the European Hematology Association
0615
COST-EFFECTIVENESS OF PEGFILGRASTIM VS. FILGRASTIM PRIMARY PROPHYLAXIS IN
PATIENTS WITH NON-HODGKINS LYMPHOMA RECEIVING CHOP-21 IN FRANCE
F. Maloisel, 1 O. Bogillot, 2 J. Malin, 3 V. Tochon, 2 Z. Liu, 4 Q. Doan, 4
A. Lalla, 4 R. Dubois4 1 2 Hospices Civils, STRASBOURG, France; Amgen S.A., PARIS, France;
3 4 Amgen Inc., THOUSAND OAKS, USA; Cerner LifeSciences, BEVERLY
HILLS, USA
Background. Primary prophylaxis (starting in the first chemotherapy
cycle and continuing for all subsequent cycles) with granulocyte-colony
stimulating factors (G-CSF) is recommended in the 2006 ASCO and
EORTC guidelines for patients with a risk of febrile neutropenia (FN)
equal to or greater than 20%. Both filgrastim (the first-generation G-
CSF, daily injections) and pegfilgrastim (the second-generation, pegylated
version of G-CSF, once per cycle) are commonly used. However, data
from certain clinical trials suggest that pegfilgrastim was associated with
a lower risk of FN compared with filgrastim. Moreover, in clinical practice
filgrastim has often been used for shorter-than-recommended courses
of administration; this has been shown to be associated with less clinical
benefit. Aims. We evaluated the cost-effectiveness of pegfilgrastim
vs. filgrastim used for 11 days (as used in the randomised trials demonstrating
efficacy) and 6 days (as often used in clinical practice) in patients
with aggressive NHL receiving CHOP-21 in France. Methods. A decisionanalytic
model was constructed from a healthcare payer’s perspective.
The study time horizon was life-time. Model inputs, including FN risk
(varied by days of filgrastim use), FN case-fatality, relative dose intensity
(RDI), and impact of RDI on survival were based on a comprehensive
literature review and expert panel validation. Costs were acquired from
official price lists or literature and included drugs, drug administration,
FN-related hospitalisations, and subsequent medical costs. NHL mortality
and all-cause mortality were obtained from official statistics. Using
data from a meta-analysis (pegfilgrastim vs. 11 days of filgrastim) and
from observational studies (pegfilgrastim vs. 6 days of filgrastim), we
estimated that the absolute risk of FN in patients receiving pegfilgrastim
decreased by 6.5 percentage points (19.6% vs. 13.1%) vs. 11-day filgrastim,
and by 12 percentage points (25.1% vs. 13.1%) vs. 6-day filgrastim.
Next, we estimated the impact of a difference in FN risk on FN-related
mortality, RDI, and long-term survival. Sensitivity analyses were used to
assess the model robustness. Outcomes were measured as incremental
cost-effectiveness ratio (ICER) including € per percentage (absolute) FN
risk decreased, € per life-year gained (LYG), and € per quality-adjusted
life-year (QALY) saved. Results. Pegfilgrastim was cost saving compared
with 11-day filgrastim (€10,457 vs. €13,081 for pegfilgrastim vs. filgrastim).
Compared with 6-day filgrastim, pegfilgrastim was associated with
?226 per additional 1% decrease in absolute risk of FN. Pegfilgrastim
achieved 7.57 LY (6.51 QALY) as compared to 7.45 LY (6.41 QALY) from
filgrastim at a moderate cost increase of €2,707 per person, yielding an
ICER of €24,387/LYG (€27,214/QALY saved) (Table 1). Results were
sensitive to the assumption of RDI impact, relative risk of FN for 6-day
filgrastim vs. pegfilgrastim and study time horizon. Summary and conclusions.
In France, pegfilgrastim was less expensive than 11-day filgrastim.
Pegfilgrastim resulted in a gain in life-years with a moderate cost increase
compared with filgrastim used for 6 days per CHOP-21 chemotherapy
cycle.
Table 1. Cost-effectiveness of pegfilgrastim vs. 6-day filgrastim.
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