Trapianto allogenico e infezioni fungine

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Gilberta Rostagno
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1 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

2 Trapianto allogenico e infezioni fungine Abstracts ASH abstracts 8 poster, 1 comunicazione orale.??????????????

3 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 there is currently no study, addressing the potential benefit of fluconazole prophylaxis in the setting of reduced-intensity conditioning (RIC) allo-sct. Methods 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.

4 Trapianto allogenico e infezioni fungine Abstract 4543, ASH 2013 Results: 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).

5 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: 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.

6 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 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 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.

7 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).

8 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 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 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.

9 Fattori di rischio ed epidemiologia delle IFI nel trapianto allogenico e uso razionale della profilassi antifungina fattori di rischio dati epidemiologici retrospettivi dati epidemiologici prospettici Come utilizzare la profilassi in modo razionale?

11 Allogenico: fattori di rischio (dati restrospettivi)

12 Fattori di rischio ed epidemiologia delle IFI nel trapianto allogenico e uso razionale della profilassi antifungina fattori di rischio dati epidemiologici retrospettivi dati epidemiologici prospettici Come utilizzare la profilassi in modo razionale?

14 Epidemiologia delle IFI nel trapianto allogenico LIMITI DEGLI STUDI RETROSPETTIVI Spesso monocentrici Epidemiologia locale Criteri diagnostici non standardizzati Esperienza e politica trapiantologica locale Profilassi e terapia della GVHD Profilassi antifungina Work up diagnostico IFI

15 Epidemiologia delle IFI nel trapianto allogenico e uso razionale della profilassi antifungina fattori di rischio dati epidemiologici retrospettivi dati epidemiologici prospettici Come utilizzare la profilassi in modo razionale?

16 PROSPETTICO MULTICENTRICO trapianti Allo mmrd Allo MUD 8.1 % 7.7 % Allo MRD 5.8 % IFI PROVATE- PROBABILI Globale Autologo 1.2 %

17 135 gg 123 gg ASPERGILLO 99 gg CANDIDA 61 gg

18 ASPERGILLO CANDIDA

36 Prevenzione infezioni fungine nel trapianto allogenico Profilassi antifungina? Riduzione fattori di rischio

37 Prevenzione infezioni fungine nel trapianto allogenico Profilassi antifungina? Riduzione fattori di rischio

38 Riduzione fattori di rischio: migliore selezione dei pazienti non in RC

39 Riduzione fattori di rischio: migliore selezione dei pazienti non in RC

40 Riduzione fattori di rischio: migliore profilassi della GVHD 1 RC

41 CICLOFOSFAMIDE (50 mg/kg gg 3 4) + MMF + TACR NEL TRAPIANTO MO APLOIDENTICO Riduzione fattori di rischio: migliore profilassi della GVHD

42 Prevenzione infezioni fungine nel trapianto allogenico Profilassi antifungina? Riduzione fattori di rischio

49 FFS p= ns

50 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

52 Quale tipo di trapianto? Quale donatore?

53 46-48 % pazienti hanno periodo osservazione < 180 giorni

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