Representative studies regarding HSCT in patients with prior IFD
| Study type and IFD before HSCT . | n . | Post-HSCT IFD relapse . | Percentage and type of secondary antifungal prophylaxis . | Main results . | Reference and year of publication* . |
|---|---|---|---|---|---|
| Prior IA: 10 proven and 38 probable; retrospective | 48 | 33% at 1 y | 85%†: 69% AMB based, 33% itraconazole | No RFs for IA relapse was identified | 8; 1998 |
| 88% mortality among relapsed IA | |||||
| Prior IA: 32 proven, 5 probable, 8 possible; retrospective | 42 | 29% vs 10% (if prior IA) at 1 y | NS | RFs for IA relapse: <30 d of antifungal therapy, BM or cord blood as source of stem cells, engraftment failure, radiologic persistence | 69; 2004 |
| Patients with prior IA had lower OS (56% vs 77%) and higher transplantation-related mortality (38% vs 21%) | |||||
| Prior IA: 49 proven, 80 probable; retrospective | 129 | 22% at 2 y | 95%†: 72% azoles,‡ 45% AMB based, 20% echinocandins | RFs for IA relapse: >20 d of neutropenia, advanced status of underlying hematologic malignancy, <6 wk from IA to HSCT, myeloablative conditioning, CMV disease, BM or cord blood as source of stem cells | 27; 2006 |
| Low risk: 0-1 RF, 6% incidence; intermediate risk: 2-3 RFs, 27% incidence; high risk: >3 RFs, 72% incidence | |||||
| Prior IFD: 18 IA, 8 invasive candidiasis, 23 undetermined; retrospective | 49 | 18% at 2 y | 88% azoles,‡ 6% echinocandins, 2% AMB based, 4% fluconazole | RFs for IFD relapse: <12 wk from IFD to HSCT, residual disease before HSCT, CMV reactivation, glucocorticoids for GVHD | 66; 2009 |
| Prior IFD: 31 IA, 5 Candida spp., 6 others (including 4 IMD); prospective, open label | 42 | 7% at 6 mo (including 1 Mucorales and 1 Scedosporium) | 100% voriconazole | Low overall mortality (24% at 12 mo) | 121; 2010 |
| Prior cryptococcosis: 6 pulmonary, 1 meningeal; retrospective | 7 | No relapses | 100%: 71% fluconazole, 29% voriconazole | No evidence of relapse and no mortality | 98; 2010 |
| Prior IFD: 4 proven, 40 probable, 46 possible; retrospective | 90 | 25% at 1 y | 100%: 53% azoles,‡ 16% echinocandins, 31% fluconazole | RFs for IFD relapse: neutropenia >18 d (HR, 7.3), grade 3-4 acute GVHD (HR, 7.6), <70 d from IFD to HSCT (HR, 4), use of fluconazole as prophylaxis (HR, 11.5) | 16; 2013 |
| Prior IMD: 20 IA, 5 Mucorales, 3 Curvularia, 2 Fusarium, 1 Basidiomycetes; retrospective | 29 | 14% at 1 y | 100%†: 93% azoles,‡ 66% echinocandins, 5% AMB based | High overall mortality (48% at 12 mo) | 15; 2013 |
| No IMD relapse post-HSCT | |||||
| Prior IPA: 21 proven, 115 probable; prospective | 136 | 27% at 1 y; 23% vs 42% in stable vs active IPA | 100%: 72% azoles,† 24% echinocandins, 4% AMB based | RFs for IPA relapse: active IPA at HSCT (HR, 2.4), immunosuppressive treatment of GVHD (HR, 2.2) | 67; 2014 |
| Active IPA was associated with higher rate of breakthrough IFDs and lower OS | |||||
| Prior IFD: 51 IA, 5 Candida spp., 3 Mucorales, 2 other IMD, 32 undetermined; prospective | 93 | 9% vs 16% at 1 y (overall vs prior IFD) | 99%, agent NS | Overall RFs for IFD: unrelated donor, cord blood, active leukemia when HSCT, prior IFD, GvHD | 122; 2014 |
| Prior IFD: 199 Candida spp., 281 IA, 50 others (including 9 Mucorales and 19 other IMD), and 295 suspected; retrospective | 825 | 24% vs 17% at 1 y (prior IFD vs controls) | NS | RFs for IFD relapse: prior IFD, older age, receipt of alemtuzumab, advanced malignancy, ATG exposure, cord blood, mismatched donor | 17; 2017 |
| Prior IFD was associated with higher overall mortality (RR, 1.33) and shorter PFS (RR, 1.24) | |||||
| Prior chronic disseminated candidiasis; retrospective | 15 | No relapses after median follow-up of 27 mo | NS | Prior chronic disseminated candidiasis did not increase time to HSCT, nor did it affect OS | 101; 2018 |
| Prior fusariosis (35 proven, 5 probable) and further immune suppression (5 HSCT); retrospective | 40 | 12.5% at end of follow-up | 80%†: 60% voriconazole, 25% AMB based, 5% posaconazole | Overall fusariosis relapse: 25% no prophylaxis vs 9% prophylaxis (P = .26) | 88; 2019 |
| Relapse in disseminated fusariosis: 100% no prophylaxis vs 12% prophylaxis (P = .03) | |||||
| All relapsed patients had persistent neutropenia and died | |||||
| Prior IPA: 5 proven/probable and 8 possible; retrospective | 13 | 46% at 2 y | Low-dose liposomal AMB or micafungin (NS percentages) | Mortality: 77% (prior IA) vs 40% (no prior IA) | 12; 2019 |
| Study type and IFD before HSCT . | n . | Post-HSCT IFD relapse . | Percentage and type of secondary antifungal prophylaxis . | Main results . | Reference and year of publication* . |
|---|---|---|---|---|---|
| Prior IA: 10 proven and 38 probable; retrospective | 48 | 33% at 1 y | 85%†: 69% AMB based, 33% itraconazole | No RFs for IA relapse was identified | 8; 1998 |
| 88% mortality among relapsed IA | |||||
| Prior IA: 32 proven, 5 probable, 8 possible; retrospective | 42 | 29% vs 10% (if prior IA) at 1 y | NS | RFs for IA relapse: <30 d of antifungal therapy, BM or cord blood as source of stem cells, engraftment failure, radiologic persistence | 69; 2004 |
| Patients with prior IA had lower OS (56% vs 77%) and higher transplantation-related mortality (38% vs 21%) | |||||
| Prior IA: 49 proven, 80 probable; retrospective | 129 | 22% at 2 y | 95%†: 72% azoles,‡ 45% AMB based, 20% echinocandins | RFs for IA relapse: >20 d of neutropenia, advanced status of underlying hematologic malignancy, <6 wk from IA to HSCT, myeloablative conditioning, CMV disease, BM or cord blood as source of stem cells | 27; 2006 |
| Low risk: 0-1 RF, 6% incidence; intermediate risk: 2-3 RFs, 27% incidence; high risk: >3 RFs, 72% incidence | |||||
| Prior IFD: 18 IA, 8 invasive candidiasis, 23 undetermined; retrospective | 49 | 18% at 2 y | 88% azoles,‡ 6% echinocandins, 2% AMB based, 4% fluconazole | RFs for IFD relapse: <12 wk from IFD to HSCT, residual disease before HSCT, CMV reactivation, glucocorticoids for GVHD | 66; 2009 |
| Prior IFD: 31 IA, 5 Candida spp., 6 others (including 4 IMD); prospective, open label | 42 | 7% at 6 mo (including 1 Mucorales and 1 Scedosporium) | 100% voriconazole | Low overall mortality (24% at 12 mo) | 121; 2010 |
| Prior cryptococcosis: 6 pulmonary, 1 meningeal; retrospective | 7 | No relapses | 100%: 71% fluconazole, 29% voriconazole | No evidence of relapse and no mortality | 98; 2010 |
| Prior IFD: 4 proven, 40 probable, 46 possible; retrospective | 90 | 25% at 1 y | 100%: 53% azoles,‡ 16% echinocandins, 31% fluconazole | RFs for IFD relapse: neutropenia >18 d (HR, 7.3), grade 3-4 acute GVHD (HR, 7.6), <70 d from IFD to HSCT (HR, 4), use of fluconazole as prophylaxis (HR, 11.5) | 16; 2013 |
| Prior IMD: 20 IA, 5 Mucorales, 3 Curvularia, 2 Fusarium, 1 Basidiomycetes; retrospective | 29 | 14% at 1 y | 100%†: 93% azoles,‡ 66% echinocandins, 5% AMB based | High overall mortality (48% at 12 mo) | 15; 2013 |
| No IMD relapse post-HSCT | |||||
| Prior IPA: 21 proven, 115 probable; prospective | 136 | 27% at 1 y; 23% vs 42% in stable vs active IPA | 100%: 72% azoles,† 24% echinocandins, 4% AMB based | RFs for IPA relapse: active IPA at HSCT (HR, 2.4), immunosuppressive treatment of GVHD (HR, 2.2) | 67; 2014 |
| Active IPA was associated with higher rate of breakthrough IFDs and lower OS | |||||
| Prior IFD: 51 IA, 5 Candida spp., 3 Mucorales, 2 other IMD, 32 undetermined; prospective | 93 | 9% vs 16% at 1 y (overall vs prior IFD) | 99%, agent NS | Overall RFs for IFD: unrelated donor, cord blood, active leukemia when HSCT, prior IFD, GvHD | 122; 2014 |
| Prior IFD: 199 Candida spp., 281 IA, 50 others (including 9 Mucorales and 19 other IMD), and 295 suspected; retrospective | 825 | 24% vs 17% at 1 y (prior IFD vs controls) | NS | RFs for IFD relapse: prior IFD, older age, receipt of alemtuzumab, advanced malignancy, ATG exposure, cord blood, mismatched donor | 17; 2017 |
| Prior IFD was associated with higher overall mortality (RR, 1.33) and shorter PFS (RR, 1.24) | |||||
| Prior chronic disseminated candidiasis; retrospective | 15 | No relapses after median follow-up of 27 mo | NS | Prior chronic disseminated candidiasis did not increase time to HSCT, nor did it affect OS | 101; 2018 |
| Prior fusariosis (35 proven, 5 probable) and further immune suppression (5 HSCT); retrospective | 40 | 12.5% at end of follow-up | 80%†: 60% voriconazole, 25% AMB based, 5% posaconazole | Overall fusariosis relapse: 25% no prophylaxis vs 9% prophylaxis (P = .26) | 88; 2019 |
| Relapse in disseminated fusariosis: 100% no prophylaxis vs 12% prophylaxis (P = .03) | |||||
| All relapsed patients had persistent neutropenia and died | |||||
| Prior IPA: 5 proven/probable and 8 possible; retrospective | 13 | 46% at 2 y | Low-dose liposomal AMB or micafungin (NS percentages) | Mortality: 77% (prior IA) vs 40% (no prior IA) | 12; 2019 |
ATG, antithymocyte globulin; BM, bone marrow; HR, hazard ratio; IA, invasive aspergillosis; IMD, invasive mold disease; NS, not specified; OS, overall survival; PFS, progression-free survival; RF, risk factor; RR, relative risk.
Arranged chronologically.
Some patients received >1 antifungal.
In this table, mold-active azoles (itraconazole, voriconazole, and posaconazole) are together referred to as azoles. If an azole without mold activity was used (eg, fluconazole), it is specified.