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

12 th Congress of the European Hematology Association
1463
SECONDARY ANTIFUNGAL PROPHYLAXIS (SAP): AN EXPERIENCE OF A BRAZILIAN
HEMATOLOGY SERVICE
L.C. Palma, M.P. Avanzi, M.I.A. Madeira, L.F. Dalmazzo,
M.C. Favarin, C.E.E. Velano, D. Brunetta, G. Navarro, F. Pieroni,
A.B. Stracieri, L.C.V. Santos, C.H. Kruzich, G.F. Perini, L.C.O. Oliveira,
L.L.P. Figueiredo, G.G. Gaspar, J.F.C. Figueiredo, J.C. Voltarelli,
E.M. Rego, B.P. Simões
HCFMRP-USP, RIBEIRÃO PRETO, Brazil
Background. Patients undergoing chemotherapy or bone marrow transplantation
(BMT) have a great risk to develop invasive fungal infections
(IFI). IFI are associated with high mortality in this group of patients and
most of them are unable to finish their planned treatment after a diagnosis
of IFI. The risk of reactivation of prior fungal infections is prohibitive
high in this situation. Therefore, in the last years, the interest in secondary
antifungal prophylaxis (SAP) has increased. This strategy may
allow the continuation of the treatment of hematological disease with
an acceptable protection against IFI relapse. Therefore, it was our objective
to relate our experience in SAP. Methods. We retrospectively analyzed
seven patients who had a proved invasive fungal infection and
used SAP. Results. The median age was 49 (7-65) years-old. There were
four cases of Aspergillus spp., one Fusarium spp., one Mucor spp. invasive
infection and one hepatosplenic candidiasis. Three patients had
acute myeloid leukemia (AML). AML patients had aspergillosis, candidiasis
and zygomycosis. Zygomycosis patient interrupted for 3
months full chemotherapy after diagnosis of IFI. After an accumulated
dose of L-Amb higher than 2000 mg, he received a reduced AML induction
protocol using amphotericin as SAP. He went well without any sign
of reactivation or progression. Two patients developed aspergillosis after
BMT. Both used voriconazole as SAP during prednisone and CyA for
GVHD treatment. One patient had received the diagnosis of AML and
had developed Fusarium spp. pneumonia during first AML induction
phase. He received a second induction treatment and used voriconazole
for two months until there had been only a small sign in chest CT. During
conditioning for allo BMT and during steroid treatment for acute
GVHD grade III we maintained him with oral voriconazole. He never
showed any sign of relapse or progression of the IFI. There was one
patient with mantle cell lymphoma who received HyperCVAD protocol
without interruption nevertheless a proven pulmonary aspergillosis
was made early during treatment. All patients with Aspergillus spp. and
Fusarium spp. infections used voriconazole as SAP. Although some of
them used the drug for months no side effects were observed. None of
them reported visual hallucination a frequent side effect described for
this drug. Mucor spp. invasive infection and hepatosplenic candidiasis
cases used amphothericin and fluconazole, respectively. Until now, no
patient has any sign of reactivation or progression. Conclusions. Prior IFI
without prophylaxis carries an unacceptable risk of relapse and death in
patients with subsequent immunossupression (Sipsas and Kontoyiannis
CID 2006). SAP should be evaluated in further studies but in our cases
it was well tolerated and until now, no patient present any sign of fungal
reactivation.
1464
IS THERE A DIFFERENCE IN THERAPY RESULTS BETWEEN ACUTE MYELOID LEUKEMIA
PATIENTS WITH MYELOBLASTIC BONE MARROW INFILTRATION WITHIN 20-29%
AND =30% AT DIAGNOSIS?
S. Grosicki, J. Holowiecki
Silesian Medical Academy, KATOWICE, Poland
Definition of acute myeloid leukemia (AML) combines groups of disorders,
which differ in pathogenesis, cytogenetics, clinical signs, results
of therapy and prognosis. They belongs to cancers of granulocyto-monocytic,
megakariocytic or erytroblastic systems and they are characterized
by bone marrow, peripheral blood and often internal organs infiltration
by clone of abnormal cells deriving from early stages of hematopoiesis.
Basic criterion of diagnosis of AML is level of bone marrow infiltration
by myeloblasts. Thirty years ago FAB (French-American-British) classification
was defined and according to this recommendation AML was
diagnosed based on morphocytochemic and immunophenotypic features
of myeloblasts with bone marrow infiltration ≥30%. In 2002 the
group of WHO investigators published new classification scheme of
AML based on cytogenetic and biomolecular features of myeloblastic
cells. They decided to decrease level of blastic bone marrow infiltration
necessary to diagnose AML to ≥20%. The remaining question was if
522 | haematologica/the hematology journal | 2007; 92(s1)
there is a difference in therapy results between two groups of AML
patients: with blastic bone marrow infiltration within 20-29% and
≥30%. We provided retrospective analysis to answer to this question.
The analysis was performed on patients population treated according to
PALG (Polish Adult Leukemia Group) protocol of DAC vs. DA study.
There were 26 cases with myeloblastic bone marrow infiltration within
20-29% (assessed group), and 379 patients with infiltration ≥30% at
diagnosis (comparative group) treated within the above mentioned
study in years 1999-2002. The patients received as induction DAC-7
regimen: daunorubicin 60 mg/m 2 /d iv 1-3; cytarabine 200 mg/m 2 /d ci 1-
7; cladribine 5 mg/m 2 2h inf. iv d 1-5 or standard DA-7 regimen (the same
regimen without cladribine). Patients achieving CR received two courses
of subsequent intensive consolidation: 1) HAM (HD AraC, mitoxantrone)
2) HD AraC with or without cladribine in the DAC-7 or DA-
7 arm, respectively. In the case of PR after the first induction course the
same regimen was repeated. Post-consolidation therapy was in both
arms comparable. In 62,5% patients (n=10) of the assessed group AML
was preceding by myelodysplastic syndrome. Complete remission (CR)
rate was comparable in both populations and reached 73% (n=19) in the
assessed group and 70% (n=264) in the comparative one. Simultaneously,
there was no statistical difference between overall survival (OS)
and leukemia free survival (LFS) in both groups. OS after 5 years reached
34% in the assessed group and 27% in the comparative one and LFS
reached 42% and 27%, respectively (p=NS). Our retrospective study
did not show any difference in therapy results between AML patients
with bone marrow infiltration within 20-29% and ≥30% at diagnosis
and it can be an additional argument to join both groups to identical therapeutic
proceedings.
1465
ELEVATED SERUM CONCENTRATIONS OF INTERLEUKIN-6 RECEPTOR AND INTERLEUKIN
1β CORRELATES WITH PCNA PROLIFERATIVE INDEX IN MULTIPLE MYELOMA
G. Tsirakis, 1 A. Sfiridaki, 2 C. Pappa, 1 R. Alexandraki, 1 E. Stavroulaki, 1
F.H. Passam, 3 E. Stathopoulos, 1 D.S. Kyriakou, 4 M.G. Alexandrakis1 1 University Hospital of Crete, HERAKLION; 2 Venizelion General Hospital,
HERAKLION; 3 Sotiria Hospital, ATHENS; 4 University Hospital of Larisa,
LARISA, Greece
Background. Various cytokines have been involved in the control of
growth and progression of multiple myeloma (MM). Among these,
Interleukin-6 (IL-6) has been recognized as the major growth factor for
human myeloma cells in vitro. Soluble IL-6 receptor (sIL-6R) is derived
from the extracellular domain of the IL-6 receptor. Increased serum levels
of sIL-6R have been found in MM patients in the early or late phase
of the disease, while patients in the plateau phase exhibit normal levels
of the receptor. Plasma cell nuclear antigen (PCNA) is a proliferative
indice whose level of expression varies during the cell cycle, beginning
in the late G1 phase and becoming maximal in the S phase. IL-1β is
regarded a potent inducer of IL-6 production by stromal cells and monocytes
and some studies have suggested an important role of IL-1β in
myeloma bone disease. Aim. The aim of this study was to determine
serum IL-1β and sIL-6R in MM patients at diagnosis and to investigate
their correlation with plasma cell infiltration and the proliferative index
PCNA. Materials and Methods. Forty-four patients with MM (24 male and
20 female, mean age 66 years) were included in the study. At the time
of serum collection 12 patients had stage I, 14 had stage II and 18 had
stage III according to the criteria of Durie and Salmon’s myeloma staging
system. Serum samples were collected before initiation of treatment.
Ten age-and sex-matched healthy volunteers were used as controls. The
measurement of IL-6R and IL-1β in the serum was performed by solidphase
sandwich enzyme-linked immunosorbent assay (ELISA), employing
monoclonal human anti IL-6R and anti IL-1β antibodies from commercially
available kits (Quantikine ® R&D systems). Paramat-embedded
bone marrow biopsy was double-immunostained with antibodies to
PCNA and CD38 using the DAKO En Vision System. Results. The mean
concentrations of IL-6r, IL-β, PCNA and infiltration in the entire group
of patients were 1350.79±644.92 ng/mL, 2.99±1.16 pg/mL, 26.59±25.30
and 4040.62±2191.68 respectively. SIl-6R, IL-1β and PCNA were significantly
different among the three stages of disease p