ISSN 1866-8836
Клеточная терапия и трансплантация

Invasive fungal diseases in adolescents and young adults after allogeneic hematopoietic stem cell transplantation

Oksana Ayzsilnieks1, Marina Popova1, Alisa Volkova1, Olga Pinegina1, Svetlana Ignatyeva2, Kirill Ekushev1, Olga Slesarchuk1, Maria Vladovskaya1, Ludmila Zubarovskaya1, Nikolay Klimko1,2, Boris Afanasyev1
1R.Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First St.Petersburg State I.Pavlov Medical University, St.Petersburg, Russia;
2Dept. of Clinical Mycology, I. Mechnikov North-Western State Medical University, St.Petersburg, Russia

Contact: Dr. Marina Popova
E-mail: marina.popova.spb@gmail.com
doi 10.18620/ctt-1866-8836-2016-5-3-71-74
Submitted 04 September 2016
Accepted 29 September 2016

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Cellular Therapy and Transplantation (CTT)
Volume 5, Number 3
Contents 

Summary

Background

Invasive fungal diseases (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still actual problem despite improving prognosis due to recent introduction of novel antifungals and diagnostic procedures. There exist only limited data on IFD in adolescents and young adults (15 to 25 y.o.) after allo-HSCT. The aim of this study focuses on clinical characteristics, risk factors and outcomes of IFD in adolescents and young adults after allo-HSCT.

Patients and Methods

121 patients after first allo-HSCT were included into a retrospective single-center study from Jan 2013 to Nov 2015 (Table 1). Their age was from 15 to 25 years old, a median of 20 years. Underlying diseases were as follows: high risk acute leukemia, 74.4%; lymphoma, 11.6%; nonmalignant diseases, 7.4%, others, 6.6%. Allo-HSCT from matched unrelated donors was performed in 62.8%, matched related donors, 24.8%, and haploidentical grafting, 12.4%. Reduced-intensity conditioning was used in 75.2% of the cases. EORTC/MSG 2008 criteria for IFD diagnosis were used, only probable and proven IFD were taken into analysis. Active diagnostic strategy, including bronchoscopy, was used before allo-HSCT, with bronchoalveolar lavage sampling in patients with CT scanning of the lung lesions. “Active IFD” was defined as IFD diagnosed just before allo-HSCT. IFD-events means a newly arising IFD, and relapse of IFD in those patients who had it before allo-HSCT.

Results

IFD was diagnosed before allo-HSCT in 19.8% of total case number (24/121): invasive aspergillosis (IA), in 15 patients, hepatosplenic candidiasis (HSC), in 5 cases, and one patient had four IFD (IA+HSC, IA + Mucormycosis, IA + PCP). Complete response to antifungal therapy was in 9 patients (37.5%), partial response, in 6 subjects (25%), and “active IFD”, in 9 patients (37.5%). For a half of cases with active IFD (41.7%), a secondary antifungal prophylaxis was performed with Voriconazole. Patients free of IFD before allo-HSCT (n=85) received primary prophylaxis with Fluconazole (70.2%) or with Voriconazole/Posaconazole (5.8%). Cumulative incidence of IFD events by two years after allo-HSCT was 15.7% (19/121), including 18 cases of new IFD, and one IA relapse. Median time to the onset of IFD event was D+43 (14 to 577). Incidence of IA was 8.4% (10/121), with median time to onset D+27.5 (14 to 577). Invasive candidiasis (IC) was documented for 1.1% of total group, with median time to onset D+226.5 (54 to 399); Pneumocystis pneumonia (PCP), 0.5% (since day+43). The main sites of infection were lungs (86.7%). Risk factors for IFD development after allo-HSCT in the patients without pre-transplant IFD were: age < 18 y.o. (p=0.03); non-malignant underlying disease (p=0.016), and acute GvHD (p=0.036). Presence of IFD before allo-HSCT (p=0.67), grade 4 neutropenia for more than 20 days (p=0.08), active underlying disease at the time of allo-HSCT (p=0.38), reactivation of CMV infection after allo-HSCT (p=0.058), relapse of underlying disease within 100 days after allo-HSCT (p=0.65), and presence of chronic GvHD (p=0.19) were not significantly associated with IFD development after allo-HSCT. Ten patients with IA (41.7%) were treated with Voriconazole as a first line therapy, all the subjects with IC, with echinocandins, and a patient with PCP was treated with Trimethoprim/Sulfamethoxazole. A 12-week overall survival (OS) from the day of IFD diagnosis post-HSCT was 68.4% (Fig.1). The 12-week OS in cases of IA was 62.5%, and the patients with IC and PCP were alive at 12 weeks after IFD diagnosis. Two-year OS rates after allo-HSCT was 70.2%. There was no statistical difference in the two-year OS for the cases with (66.7%) or without IFD (71.1%) detected before allo-HSCT (p=0.91).

Conclusions

Incidence of IFD in adolescents and young adults before allo-HSCT was 19.8 %. Cumulative incidence of IFD at 2 years after allo-HSCT was 15.7%. The main type of IFD was invasive aspergillosis (62.5%). Only one patient with IA before allo-HSCT had a relapse of mycosis (5.3%). Risk factors for IFD after allo-HSCT (p < 0.05) were: age < 18 y.o., non-malignant underlying disease, and acute GvHD. 12-week OS value after the post-transplant IFD diagnosis was 68.4%. Due to effective diagnosis, timely treatment and secondary prophylaxis, the invasive fungal diseases, either before or after allo-HSCT, did not impair the outcome of HSCT in adolescents and young adults.

Keywords

Allo-hsct, invasive fungal disease, adolescents and young adults, aspergillosis, pre-transplant mycosis, overall survival


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