Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections
Abstract
1. Introduction
2. Materials and Methods
2.1. Setting, Patients and Study Design
2.2. Definitions
2.3. Statistical Analysis
3. Results
3.1. Characteristics and Outcomes of Patients’ Cohort
3.2. Characteristics and Outcomes of Patients with Probable and Proven IFIs
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Patients (n = 163) N (%) |
---|---|
Age (years) median (IQR) | 50 (38–63) |
Sex, male | 95 (58.3) |
Charlson comorbidity index score ≥ 3 | 73 (44.8) |
Underlying disease | |
Acute myelogenous leukemia | 76 (46.6) |
Acute lymphoblastic leukemia | 20 (12.3) |
Non-Hodgkin lymphoma | 16 (9.8) |
Myelodysplastic syndrome | 8 (4.9) |
Hodgkin lymphoma | 11 (6.7) |
Aplastic anemia | 9 (5.5) |
Chronic myelogenous leukemia | 6 (3.7) |
Chronic lymphoblastic leukemia | 4 (2.4) |
Multiple myeloma | 7 (4.3) |
Others | 6 (3.7) |
Disease status | |
Complete remission | 38 (23.3) |
Partial remission | 8 (4.9) |
Relapsed | 33 (20.2) |
Refractory | 18 (11) |
Recently diagnosed | 66 (40.5) |
HCT | 49 (30.1) |
Allogeneic | 30 (18.4) |
HLA matching and donor type | |
Haploidentical | 15 (9.2) |
Matched unrelated donor | 5 (3.1) |
Matched related donor | 10 (6.1) |
T-cell depletion | 9 (5.5) |
Acute GvHD | 13 (7.9) |
Grade I | 2 (1.2) |
Grade II | 4 (2.4) |
Grade III | 7 (4.3) |
Grade IV | 0 (0) |
Chronic GvHD | 7 (4.3) |
Variables | Patients (n = 163) N (%) |
---|---|
IFI classification | |
Proven | 22 (13.5) |
Probable | 44 (26.9) |
Possible | 97 (59.5) |
IFI location | |
Lungs | 147 (90.2) |
Paranasal sinuses | 23 (14.1) |
Liver | 5 (3.1) |
Skin and soft tissue | 5 (3.1) |
Central nervous system | 3 (1.8) |
Disseminated | 3 (1.8) |
Lung CT scan | |
Nodules | 89 (54.6) |
Ground glass appearance | 59 (36.2) |
Halo sign | 37 (22.7) |
Tree in bud | 22 (13.5) |
Alveolar infiltrate | 14 (8.6) |
Cavity | 3 (1.8) |
Air crescent sign | 1 (0.6) |
Reverse halo sign | 1 (0.6) |
Variable | Total (n = 66) | Non-bIFI (n = 31) | bIFI (n = 35) | p-Value |
---|---|---|---|---|
Age, median (IQR) | 47 (39–61) | 54 (43–67) | 44 (36–52) | 0.014 |
Male sex–n (%) | 40 (60.6) | 16 (51.6) | 24 (68.6) | 0.159 |
Charlson comorbidity index ≥ 3–n (%) | 29 (43.9) | 17 (54.8) | 12 (34.3) | 0.093 |
Underlying disease–n (%) | ||||
Acute myelogenous leukemia | 23 (34.8) | 11 (35.5) | 12 (34.3) | 0.918 |
Acute lymphoblastic leukemia | 7 (10.6) | 1 (3.2) | 6 (17.1) | 0.41 |
Myelodysplastic syndrome | 7 (10.6) | 2 (6.4) | 5 (14.3) | 0.433 |
Non-Hodgkin lymphoma | 4 (6.1) | 4 (12.9) | 0 (0) | 0.043 |
Hodgkin lymphoma | 10 (15.1) | 4 (12.9) | 6 (17.1) | 0.738 |
Multiple myeloma | 7 (10.6) | 5 (16.1) | 2 (5.7) | 0.239 |
Disease status–n (%) | ||||
Complete remission | 16 (24.2) | 5 (16.1) | 11 (31.4) | 0.165 |
Partial remission | 4 (6.1) | 1 (3.2) | 3 (8.6) | 0.616 |
Relapsed | 17 (25.8) | 9 (29) | 8 (22.9) | 0.567 |
Refractory | 9 (13.6) | 7 (22.6) | 2 (5.7) | 0.071 |
Recently diagnosed | 20 (30.3) | 9 (29) | 11 (31.4) | 0.832 |
HCT–n (%) | 27 (40.9) | 9 (29) | 18 (51.4) | 0.064 |
Allogeneic | 13 (19.7) | 4 (12.9) | 9 (25.7) | 0.228 |
Corticosteroid use–n (%) | 24 (364) | 11 (35.5) | 13 (37.1) | 0.888 |
Biological agents–n (%) | 15 (22.7) | 7 (22.6) | 8 (22.9) | 0.978 |
Antilymphocyte drugs–n (%) | 12 (18.2) | 3 (9.7) | 9 (25.7) | 0.117 |
Neutropenia–n (%) | 48 (72.7) | 21 (67.7) | 27 (77.1) | 0.392 |
Antifungal prophylaxis–n (%) | 35 (53) | 0 (0) | 35 (100) | – |
Fluconazole | 13 (19.7) | 0 (0) | 13 (37.1) | – |
Posaconazole | 10 (15.1) | 0 (0) | 10 (28.6) | – |
Voriconazole | 2 (3) | 0 (0) | 2 (5.7) | – |
L-AmB | 5 (7.6) | 0 (0) | 5 (14.3) | – |
LC-AmB | 2 (3) | 0 (0) | 2 (5.7) | – |
Caspofungin | 3 (4.5) | 0 (0) | 3 (8.6) | – |
Variable | Total (n = 66) | Non-bIFI (n = 31) | bIFI (n = 35) | p-Value |
---|---|---|---|---|
Type of IFI–n (%) | ||||
Aspergillosis | 43 (65.1) | 22 (70.9) | 21 (60) | 0.351 |
Mucormycosis | 8 (12.1) | 2 (6.4) | 6 (17.1) | 0.265 |
Fusariosis | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Other hyalo or phaeohyphomycosis | 5 (7.6) | 2 (6.4) | 3 (8.6) | 1 |
Histoplasmosis | 1 (1.5) | 1 (2.9) | 0 (0) | 0.470 |
Cryptococcosis | 1 (1.5) | 1 (2.9) | 0 (0) | 0.470 |
Unidentified hyphae | 8 (12.1) | 3 (9.7) | 5 (14.3) | 0.713 |
Microscopic detection–n (%) | 16 (24.2) | 9 (29) | 7 (20) | 0.245 |
Septate branched hyphae | 10 (15.1) | 7 (22.6) | 3 (8.6) | 0.170 |
Coenocytic hyphae | 5 (7.6) | 1 (3.2) | 4 (11.4) | 0.360 |
Cryptococcus yeast | 1 (1.5) | 1 (3.2) | 0 (0) | 0.470 |
Culture isolates–n (%) | ||||
Alternaria sp. | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Aspergillus sp. | 3 (4.5) | 1 (3.2) | 2 (5.7) | 1 |
Aspergillus flavus complex | 5 (7.6) | 2 (6.4) | 3 (8.6) | 1 |
Aspergillus fumigatus complex | 5 (7.6) | 4 (12.9) | 1 (2.9) | 0.178 |
Aspergillus niger | 3 (4.5) | 2 (6.4) | 1 (2.9) | 0.596 |
Cryptococcus neoformans var. neoformans | 1 (1.5) | 1 (2.9) | 0 (0) | 0.470 |
Cunninghamella sp. | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Curvularia sp. | 2 (3) | 2 (6.4) | 0 (0) | 0.216 |
Fusarium sp. | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Penicillium sp. | 2 (3) | 0 (0) | 2 (5.7) | 1 |
Rhizopus sp. | 2 (3) | 0 (0) | 2 (5.7) | 1 |
Rhizopus microsporum | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Rhizopus oryzae | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Rhizopus arrhizus | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
Aspergillus GM–n (%) | ||||
Positive in serum | 12 (18.2) | 5 (16.1) | 7 (20) | 0.684 |
Positive GM in BAL | 17 (25.8) | 9 (29) | 8 (22.9) | 0.567 |
Positive serum + BAL GM | 6 (9.1) | 3 (9.7) | 3 (8.6) | 1 |
Histoplasma urinary antigen–n (%) | 1 (1.5) | 1 (2.9) | 0 (0) | 0.470 |
Histopathology–n (%) | ||||
Hyphal invasion of blood vessels | 7 (10.6) | 3 (9.7) | 3 (8.6) | 1 |
Septate branched hyphae | 5 (7.6) | 3 (9.7) | 2 (5.7) | 0.659 |
Coenocytic hyphae | 6 (9.1) | 2 (6.4) | 4 (11.4) | 0.676 |
Yeast | 1 (1.5) | 1 (3.2) | 0 (0) | 0.470 |
Variable | Total (n = 66) | Non-bIFI (n = 31) | bIFI (n = 35) | p-Value |
---|---|---|---|---|
ISA treatment modality-n (%) | ||||
Preemptive therapy | 39 (59.1) | 17 (54.8) | 22 (62.9) | 0.508 |
Targeted therapy | 29 (43.9) | 14 (45.2) | 15 (42.8) | 0.851 |
Treatment with ISA–n (%) | ||||
As first-line therapy | 31 (46.9) | 16 (51.6) | 15 (42.9) | 0.477 |
As continuation therapy | 35 (53%) | 15 (48.4) | 20 (57.1) | 0.477 |
Other first-line therapy–n (%) | ||||
L-AmB | 23 (34.8) | 8 (25.8) | 15 (42.9) | 0.147 |
LC-AmB | 1 (1.5) | 1 (3.2) | 0 (0) | 0.470 |
Voriconazole | 11 (16.7) | 8 (25.8) | 3 (8.6) | 0.097 |
Posaconazole | 1 (1.5) | 1 (3.2) | 0 (0) | 0.470 |
Fluconazole | 1 (1.5) | 1 (3.2) | 0 (0) | 0.470 |
Caspofungin | 1 (1.5) | 0 (0) | 1 (2.9) | 1 |
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Herrera, F.; Torres, D.; Mendez, G.; Mañez, N.; Jordán, R.; Manzur, A.; Cabral, M.; Alderete, M.; García Allende, N.; Benso, J.; et al. Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections. J. Fungi 2025, 11, 648. https://doi.org/10.3390/jof11090648
Herrera F, Torres D, Mendez G, Mañez N, Jordán R, Manzur A, Cabral M, Alderete M, García Allende N, Benso J, et al. Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections. Journal of Fungi. 2025; 11(9):648. https://doi.org/10.3390/jof11090648
Chicago/Turabian StyleHerrera, Fabián, Diego Torres, Gustavo Mendez, Noelia Mañez, Rosana Jordán, Adriana Manzur, Myrna Cabral, Manuel Alderete, Natalia García Allende, José Benso, and et al. 2025. "Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections" Journal of Fungi 11, no. 9: 648. https://doi.org/10.3390/jof11090648
APA StyleHerrera, F., Torres, D., Mendez, G., Mañez, N., Jordán, R., Manzur, A., Cabral, M., Alderete, M., García Allende, N., Benso, J., Salgueira, C., Pereyra, M. L., Peretti, H., Niveyro, C., Castro, M., Pollastrelli, F., García Rojas, S., Dapás, J., Risso Patrón, A., ... Afeltra, J., on behalf of Multicenter study on Isavuconazole for Treatment and Prophylaxis of Invasive Fungal Infections in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation (EMISA). (2025). Isavuconazole Therapy for Patients with Hematologic Diseases and Hematopoietic Cell Transplantation with and Without Breakthrough Invasive Fungal Infections. Journal of Fungi, 11(9), 648. https://doi.org/10.3390/jof11090648