SOD CLINICA DI EMATOLOGIA
OSPEDALI RIUNITI DI ANCONA
PROGRAMMA TRAPIANTO DI CELLULE STAMINALI EMOPOIETICHE
Accreditamento JACIE – CNT/CNS
Trapianto allogenico e infezioni fungine
Dr. Mauro Montanari
Trapianto allogenico e infezioni fungine
Abstracts ASH 2013
• 9 abstracts……
• 8 poster, 1 comunicazione orale….
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Trapianto allogenico e infezioni fungine
Abstract 4543, ASH 2013
Prolonged Fluconazole Prophylaxis Is Not Required In Patients With Acute Leukemias Or
Myelodysplastic/Myeloproliferative Disorders After Reduced-Intensity Conditioning (RIC)
Allogeneic Stem Cell Transplantation (allo-SCT): A Pair-Matched Analysis
Introduction
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there is currently no study, addressing the potential benefit of fluconazole prophylaxis in the
setting of reduced-intensity conditioning (RIC) allo-SCT.
Methods
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retrospective study
105
patients
with
acute
leukemia
(AML,
n=55,
ALL,
n=11)
or
myelodysplastic/myeloproliferative disorders (MDS, n=24; myeloproliferative disorder n=15)
patients received RIC allo-SCT and PBSC as stem cell source for all.
among these 109 procedures, we compared those cases receiving (n=53) or not (n=56)
fluconazole prophylaxis after transplant.
Trapianto allogenico e infezioni fungine
Abstract 4543, ASH 2013
Results:
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No significant differences in term of cumulative incidences of acute grade II-IV GVHD or
chronic GVHD
Before day +100, only 2 Aspergillus infections were documented in the fluconazole group vs
4 in the non-fluconazole group (P=NS). No Candida infections developed in the fluconazole
group compared to 2 in the non-fluconazole group (P=NS).
After day +100, Aspergillus infections were documented in 5 patients in the fluconazole group
versus 3 in the non-fluconazole group (P=NS).
The number of patients receiving pre-emptive or curative antifungal treatment (voriconazole,
caspofungin or ambisome) after transplant was higher in the non-fluconazole group (52% of
cases vs 34%, P=0.09).
Trapianto allogenico e infezioni fungine
Abstract 4543, ASH 2013
Prolonged Fluconazole Prophylaxis Is Not Required In Patients With Acute Leukemias Or
Myelodysplastic/Myeloproliferative Disorders After Reduced-Intensity Conditioning (RIC)
Allogeneic Stem Cell Transplantation (allo-SCT): A Pair-Matched Analysis
Conclusion:
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This is the first series reporting the comparison of the use or not of fluconazole as prophylaxis
after RIC allo-SCT. Our results showed that the use of fluconazole has no impact in term of
fungal infections or overall outcomes after RIC allo-SCT, suggesting that fluconazole is not
required after RIC allo-SCT. Large prospective studies are warranted to further confirm this
important therapeutic issue.
Trapianto allogenico e infezioni fungine
Abstract 4541, ASH 2013
Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections
Compared To Unrelated Bone Marrow:
A Single Center Retrospective Analysis For 749 Recipients
Background
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Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell
transplantation (HSCT), the risk of which is considered to be particularly prominent among cord
blood transplantation (CBT) recipients.
Patients and methods
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We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated
bone marrow transplantation (uBMT) for the first time and who had neither prior history nor
suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ)
capsules were conventionally used until around 2006, which were then changed to newer moldactive agents including ITCZ oral solution, voriconazole or micafungin after their approval in
Japan, the choice of which was subjected to physician's discretion.
Trapianto allogenico e infezioni fungine
Abstract 4541, ASH 2013
Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections
Compared To Unrelated Bone Marrow:
A Single Center Retrospective Analysis For 749 Recipients
Results
The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT
patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower
thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar
between the 2 groups (12.6% vs 11.6%, P=0.58).
Trapianto allogenico e infezioni fungine
Abstract 4541, ASH 2013
Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections
Compared To Unrelated Bone Marrow:
A Single Center Retrospective Analysis For 749 Recipients
Results
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Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day
were identified as significant risk factors of IFIs for both groups. However, the impact of all these
were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in
contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR
2.87, P=0.03).
Conclusion
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Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the
early post-transplant period was counterbalanced by the dramatically decreased risk due to
lower frequencies of GVHD and its treatment in the later period.
Fattori di rischio ed epidemiologia
delle IFI nel trapianto allogenico
e uso razionale della profilassi antifungina
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fattori di rischio
dati epidemiologici retrospettivi
dati epidemiologici prospettici
Come utilizzare la profilassi in modo razionale ?
Allogenico:
fattori di rischio
(dati restrospettivi)
Fattori di rischio ed epidemiologia
delle IFI nel trapianto allogenico
e uso razionale della profilassi antifungina
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•
•
fattori di rischio
dati epidemiologici retrospettivi
dati epidemiologici prospettici
Come utilizzare la profilassi in modo razionale ?
Epidemiologia delle IFI nel trapianto allogenico
LIMITI DEGLI STUDI RETROSPETTIVI
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Spesso monocentrici
Epidemiologia locale
Criteri diagnostici non standardizzati
Esperienza e politica “trapiantologica” locale
Profilassi e terapia della GVHD
Profilassi antifungina
Work up diagnostico IFI
Epidemiologia delle IFI nel trapianto allogenico
e uso razionale della profilassi antifungina
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fattori di rischio
dati epidemiologici retrospettivi
dati epidemiologici prospettici
Come utilizzare la profilassi in modo razionale ?
PROSPETTICO
MULTICENTRICO
2001-2008
15820 trapianti
Allo mMRD
Allo MUD
Allo MRD
7.7 %
5.8 %
IFI
PROVATEPROBABILI
Globale
1.2 %
Autologo
8.1 %
135 gg
123 gg
ASPERGILLO
CANDIDA
99 gg
61 gg
CANDIDA
ASPERGILLO
Prevenzione infezioni fungine
nel trapianto allogenico
Profilassi
antifungina
?
Riduzione
fattori
di rischio
Prevenzione infezioni fungine
nel trapianto allogenico
Profilassi
antifungina
?
Riduzione
fattori
di rischio
Riduzione fattori di rischio:
migliore selezione dei
pazienti non in RC
Riduzione fattori di rischio:
migliore selezione dei
pazienti non in RC
Riduzione fattori di rischio:
migliore profilassi della
GVHD
1 RC
CICLOFOSFAMIDE (50 mg/kg gg 3 – 4) + MMF + TACR
NEL TRAPIANTO MO APLOIDENTICO
Riduzione fattori di rischio:
migliore profilassi della
GVHD
Prevenzione infezioni fungine
nel trapianto allogenico
Profilassi
antifungina
?
Riduzione
fattori
di rischio
FFS
p= ns
GIRMENIA LETTER…
Voriconazole prophylaxis and the risk of invasive fungal infection after
allogeneic HCT
Corrado Girmenia, MD
Franco Aversa, Alessandra Micozzi, Simone Cesaro, Francesco Giuseppe De
Rosa, Malgorzata Mikulska, Maurizio Sanguinetti, Andrea Novelli and
Claudio Viscoli
Dipartimento di Ematologia, Azienda Policlinico Umberto I, Rome, Italy
Quale tipo di trapianto ? Quale donatore ?
46-48 % pazienti hanno periodo osservazione < 180 giorni