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Abstract

Patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) are typically placed in a laminar air flow room until hematopoietic reconstitution occurs. In this study, we compared the differences in clinical outcomes between patients receiving allo-HSCT in a conventional laminar flow room (n = 200) and those receiving allo-HSCT in a plasma sterilizer environment (n = 201). The overall infection rates (20.4% vs 25.5%, P = 0.224) and the sites of infection (sepsis, perianal infection, and catheter-related infection) were comparable between the two groups. Additionally, the engraftment times were comparable between the two groups in terms of time to allo-HSCT, leukocyte engraftment time, and platelet engraftment time. The 100-day posttransplantation clinical outcomes were also comparable between the two groups in terms of the probability of overall survival (98.5% vs 99.5%, P = 0.316), leukemia-free survival (96.5% vs 96.5%, P = 0.991), the cumulative incidence of relapse (2.0% vs 3.0%, P = 0.523), non-relapse mortality (1.5% vs 0.5%, P = 0.316) and acute graft-versus-host disease (23.4% vs 22.0%, P = 0.723). Thus, our results demonstrated that receiving allo-HSCT via a plasma sterilizer did not increase the risk of pre-engraftment infection, and the clinical outcomes of these patients were comparable to those of patients in a conventional laminar flow room.

Graphical Abstract

Keywords

hematopoietic stem cell transplantation laminar flow room efficient and cost-effective disinfection machine plasma sterilizer

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective and is often the only curative treatment for many hematologic malignancies^1–5. The conditioning regimen involves high-dose chemotherapy and/or radiotherapy and is performed to maximize the elimination of tumor cells and create an optimal environment for the engraftment of donor hematopoietic stem cells. During the time period before granulocyte engraftment (which occurs for 2–3 weeks), patients experience severe granulocytopenia and are highly immunocompromised, thus rendering them vulnerable to various infections. A series of studies have reported a close relationship between infections and engraftment outcomes^6–10. Specifically, preengraftment intestinal infections have been observed to significantly increase the risk of 100-day acute graft-versus-host disease (GVHD)^11–14, and the overall mortality rate for patients with preengraftment bloodstream infections was observed to be as high as 21% within 120 days posttransplantation. These findings underscore the critical impact of preengraftment infections on patient prognosis. Therefore, the maintenance of a highly clean and sterile environment during the granulocyte-deficient preengraftment period is essential to prevent infection and improve outcomes.

A conventional laminar air flow room (LAFR) can achieve 100-level air cleanliness by using primary, medium- and high-efficiency filters to remove pathogenic microorganisms and airborne particles. Clinical practices have demonstrated that this clean technology is an effective measure for preventing various infections and for specifically significantly reducing nosocomial infections^15,16. Recent advancements in science and technology have led to the development of plasma sterilizers (also known as high-efficiency disinfectors), which ionize the air via corona discharge, thus generating plasma that inactivates and filters out pathogenic microorganisms. Compared with traditional laminar flow rooms, plasma sterilizers offer several advantages, including enhanced patient comfort, energy efficiency, ease of maintenance, high stability, quantifiable sterilization efficacy, and the ability for the adjustment or relocation of the sterilizer based on clinical needs. These benefits not only improve the conditions of patients but also reduce both patient health care costs and hospital maintenance expenses (Supplementary Table 1). Several studies in China have demonstrated that, in immunocompromised populations (such as adult and pediatric hematology patients), the use of the abovementioned plasma sterilizers can effectively prevent infections during the granulocyte deficiency stage^17,18. However, it remains unclear as to whether allo-HSCT performed in a plasma sterilizer environment can achieve clinical outcomes comparable to those in conventional laminar airflow rooms.

Thus, this retrospective study was conducted to compare the incidence of infection, engraftment, and prognosis between patients who received allo-HSCT in plasma sterilizer environments and those who received allo-HSCT in conventional laminar flow rooms.

Methods

Patients

Patients who received allo-HSCT in the conventional laminar flow room from January to December 2022 (200 patients) and those who received allo-HSCT in a plasma sterilizer environment from May to December 2023 (201 patients) were consecutively enrolled in this study. The last follow-up was December 2024.

Data collection

The investigators utilized the institutional electronic medical records of clinical databases to obtain the required information. The collected data included information on patient demographics, diagnosis, disease status before allo-HSCT, transplant regimen, donor type, occurrence of infections (including pathogens, sites of infection, and time of occurrence, among other data), engraftment, GVHD status and clinical outcomes (including relapse, mortality, and survival).

Environmental monitoring methods

Sampling timing of new wards

Prior to testing, all of the rooms were thoroughly cleaned and disinfected, after which they were sealed off to prevent personnel entry. The laminar airflow clean room purification system was checked to ensure normal operation for 24 hours before the procedure was conducted. During the first three months after the operation, cleanliness and dynamic bacterial concentration tests were performed on a monthly basis in room 4. Static air quality was tested using the sedimentation method in rooms 2 and 3, as well as on ultraclean tables and in biosafety cabinets. Microbial sampling and culturing were conducted across all types of environments. Once the ward’s operation was stabilized, testing was conducted on a quarterly basis.

Sampling method

The environmental monitoring points were established according to the ISO 9000 “Quality Management and Quality Assurance” standards and were based on the guidelines provided by the Infection Control Department of our institution. To monitor the cleanliness of room 4, three sampling points were established and positioned at diagonal corners of the room. Air quality was assessed using the sedimentation method. In room 4, one Petri dish was placed at the head of each bed, whereas in room 3, at least three Petri dishes were placed. In room 2, at least 18 Petri dishes were placed along the corridors. For ultraclean tables and biosafety cabinets, a minimum of one Petri dish was placed at each unit. Surface monitoring involved sampling tests at various surfaces, with at least three surfaces sampled in room 4, three surfaces sampled in room 3 (with a focus on high-frequency contact areas such as ultraclean tables, monitors, infusion pumps, infusion racks, and infusion carts), and at least 10 surfaces sampled in room 2 (such as nurse station countertops, computer mice, keyboards, telephones, and treatment room refrigerators).

Statistical analysis

Frequencies and percentages were used to describe the characteristics of the patients. The Mann-Whitney U test was used to compare continuous variables, and the chi-square test and Fisher’s exact test were used to compare categorical variables. The Kaplan–Meier estimator was used to calculate the probabilities of overall survival (OS) and leukemia-free survival (LFS). The cumulative incidence function was used to calculate the incidence of relapse and non-relapse mortality (NRM) via competing risk analysis. Univariable and multivariable Cox regression analyses were performed to determine the impacts of potential prognostic factors on infection status. A two-sided statistical test was utilized, and P < 0.05 was considered to be statistically significant. Tests were performed using SPSS (2023) and R software.

Results

General information

A total of 401 patients were enrolled in this study; moreover, 201 and 200 patients were categorized into the plasma sterilizer and conventional laminar flow room groups, respectively (Table 1). A total of 31 plasma sterilizers in this ward were monitored in terms of particulate matter, microorganisms and object surfaces. A Class-100-standard laminar standard flow cleanroom met the Class 100 cleanliness standard, which stipulates that the maximum particle concentration of airborne particles ≥ 0.5 μm in diameter should not exceed 100 particles per cubic foot (approximately 3,520 particles per cubic meter). Thus, the number of particles ≥ 0.5 μm in diameter per cubic foot of air should be limited to 100 particles. The monitoring results of both laminar flow chambers met the Class 100 standard (Table 2).

Table 1.

Patient characteristics.

Characteristics	Conventional laminar flow room group	Plasma sterilizer group	P value
Median age (range)	38 (5–68)	38 (7–66)	0.602
Gender, n (%)			0.875
Male	112 (55.7)	113 (56.5)
Female	89 (44.3)	87 (43.5)
Underlying disease			0.074
Acute leukemia	147 (73.1)	122 (61.0)
Chronic leukemia	10 (5.0)	8 (4.0)
Myelodysplastic syndrome	22 (10.9)	34 (17.0)
Lymphoma	11 (5.5)	19 (9.5)
Others	11 (5.5)	17 (8.5)
Type of donor, n (%)			0.814
HLA-matched donor	36 (17.9)	38 (19.0)
Haploidentical donor	151 (75.1)	151 (75.5)
Unrelated donor	14 (7.0)	11 (5.5)
Donor-recipient sex matched			0.484
Female donor/Male patient	30 (14.9)	35 (17.5)
Others	171 (85.1)	165 (82.5)
Donor-patient relationship, n (%)			0.908
Father	12 (6.0)	11 (5.5)
Mother	51 (25.4)	50 (25.0)
Sibling	63 (31.3)	63 (31.5)
Child	57 (28.4)	56 (28.0)
Collateral	4 (2.0)	8 (4.0)
Unrelated donor	14 (7.0)	12 (6.0)
ABO-matched graft, n (%)			0.682
Matched	111 (55.2)	106 (53.0)
Major mismatched	26 (12.9)	32 (16.0)
Miner mismatched	64 (31.8)	62 (31.0)
Chemotherapy before allo-HSCT			0.150
No	24 (11.9)	34 (17.0)
Yes	177 (88.1)	166 (83.0)
HCT-CI scores before allo-HSCT, n (%)			0.201
0 (low risk)	101 (50.3)	118 (59.0)
1–2 (intermediate risk)	81 (40.3)	68 (34.0)
≥ 3 (high risk)	19 (9.4)	14 (7.0)
Individual comorbidities as defined by the HCT-CI
Arrhythmia or Cardiac	17 (8.5)	17 (8.5)	0.988
Inflammatory bowel disease	1 (0.5)	1 (0.5)	1.000
Diabetes	14 (7.0)	11 (5.5)	0.544
Hepatic	25 (12.5)	20 (10.0)	0.439
Infection	4 (2.0)	3 (1.5)	1.000
Peptic ulcer	1 (0.5)	0 (0)	1.000
Moderate/severe pulmonary	19 (9.5)	22 (11.0)	0.609
Moderate/severe renal	5 (2.5)	3 (1.5)	0.726
Prior malignancy	14 (7.0)	8 (4.0)	0.192
Cerebrovascular disease	2 (1.0)	2 (1.0)	1.000
Conditioning regimens			0.991
Chemotherapy-based regimen	192 (95.5)	191 (95.5)
TBI-based regimen	9 (4.5)	9 (4.5)
MNC counts in graft, median (×10^8/kg)	9.01 (3.00–32.03)	9.98 (1.52–26.52)	< 0.001
CD34+ counts in graft, median (×10^6/kg)	4.17 (0.66–20.03)	3.60 (0.67–77.09)	0.113
Median time of neutrophil engraftment, days (range)	14 (6–43)	13 (0–45)	0.449
Median time of platelet engraftment, days (range)	15 (4–275)	15 (8–144)	0.439
Median time in conventional laminar flow room or plasma sterilizer, days (range)	29 (19–66)	27 (17–55)	< 0.001

HCT-CI: hematopoietic cell transplantation-specific comorbidity index.

Table 2.

Pathogen microorganisms and particulate matter monitoring results.

Days after use	Monitoring items	Monitoring scope	Number of sampling points	Monitoring results
Before use	Static cleanliness test	Sampling test 8 rooms 4	24	Passed
Before use	Bacteria concentration test with Static sedimentation method	Room 2, room 3, room 4 and ultraclean table	244	Beds 8 and 9 in room 4,2 CNS cultured,Failed
Before use	Microbiology testing of static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	154	Passed
Retesting before use	Microbiology testing of static environmental surfaces	Bed 8 and bed 9 in room 4	8	Retesting passed
Before use	Static cleanliness test	Cleanliness test of room 4	31	passed
Before use	Bacteria concentration test with dynamic plankton method	Sampling test for 8 rooms 4	16	passed
1 month after use	Microbiology testing of static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	55	passed
1 month after use	Bacteria concentration test with dynamic plankton method	31 rooms 4	58	passed
2 months after use	Bacteria concentration test with static sedimentation method	Sampling test of room 3 and room 4	14	passed
2 months after use	Microbiology testing of Static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	78	passed
2 months after use	Bacteria concentration test with Dynamic Plankton Method	31 rooms 4	64	passed
3 months after use	Bacteria concentration test with Dynamic Plankton Method	Sample test 12 rooms 4	48	passed
3 months after use	Microbiology testing of Static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	100	passed
5 months after use	Bacteria concentration test with Dynamic Plankton Method	Sample test 12 rooms 4	48	passed
5 months after use	Microbiology testing of Static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	100	passed
7 months after use	Bacteria concentration test with Dynamic Plankton Method	Sample test 12 rooms 4	48	passed
7 months after use	Microbiology testing of Static environmental surfaces	Room 2, room 3, room 4 and ultraclean table	100	passed

Overall infections

During the period when the patient was residing in the laminar flow room, there was no significant difference observed between the two groups of patients in terms of the incidence of infection, the time of occurrence of posttransplantation infections, or the types of detected pathogens (Fig. 1). Moreover, when the incidence of each major infection site was analyzed (such as the incidences of lung infection, perianal infection, catheter-related bloodstream infection and sepsis), the time of occurrence was not significantly different, except for the time of occurrence of perianal infection to the time of transplantation (P = 0.046); additionally, the other sites were not significantly different (Table 3). According to the multivariate analysis, ABO-mismatched grafts increased the risk of infection after allo-HSCT in the plasma sterilizer group, and MNC counts ≤ the median increased the risk of infection after allo-HSCT in both the plasma sterilizer group and the total cohort. Female donors to male recipients demonstrated increased risks of more than one type of infection in the conventional LAFR group. MNC counts ≤ the median also increased the risks of bacterial infection in the plasma sterilizer group and total cohort. HCT-confidence interval (CI) score ≥ 3 increased the risks of more than one type of infection and fungal infection in the plasma sterilizer group. The absence of chemotherapy before allo-HSCT was associated with an increased risk of fungal infection in the total cohort (Tables 4 and 5).

Figure 1.

The types of detected pathogens in the conventional laminar flow room group and plasma sterilizer group. (a) In the conventional laminar flow room group. (b) In the plasma sterilizer group.

Table 3.

Infections characteristics of plasma sterilizer and conventional laminar flow room groups.

	Conventional laminar flow room group	Plasma sterilizer group	P value
Infection in laminar flow room
Overall infection, n (%)	41 (20.4)	51 (25.5)	0.073
Median time to transplantation for onset of infection	21 (4–28)	19 (4–38)	0.231
Pathogen of infection			0.108
Klebsiella pneumoniae	7(3.5)	14 (7.0)	0.114
Escherichia coli	9 (4.5)	14 (7.0)	0.227
Lung infection, n (%)	8 (4.0)	16 (8.0)	0.090
Median time to transplantation for occurrence of pneumonia	20 (12–26)	19.5 (2–29)	0.782
Pneumonia pathogen			0.849
Klebsiella pneumoniae	2 (25.0)	6 (37.5)
Fungus	1 (12.5)	3 (18.8)
No pathogenic bacteria detected	5 (62.5)	7 (43.8)
Perianal infections, n (%)	10 (5.0)	19 (9.5)	0.080
Median time to transplantation for occurrence of perianal infections	18.5 (11–28)	13 (1–25)	0.046
Perianal infection pathogen			0.827
Klebsiella pneumoniae	1 (9.1)	2 (11.1)
Escherichia coli	5 (45.5)	8 (44.4)
bacillus subtilis	1 (9.1)	1 (5.6)
Enterococcus faecalis	1 (9.1)	0
Others	3 (27.3)	7 (38.9)
Catheter-associated bloodstream infections, n (%)	16 (8.0)	27 (13.5)	0.073
Median time to transplantation for occurrence of catheter-associated infections	21 (4–28)	19 (4–38)	0.231
Catheter-associated infection pathogens			0.350
Klebsiella pneumoniae	0	4 (33.3)
Escherichia coli	1 (16.7)	0
Staphylococcus epidermidis	3 (50.0)	2 (16.7)
Streptococcus pyogenes	1 (16.7)	1 (8.3)
Enterococcus faecalis	0	2 (16.7)
Pseudomonas aeruginosa	0	1 (8.3)
Others	1 (16.7)	2 (16.7)
Bloodstream infections, n (%)	16 (8.0)	27 (13.5)	0.073
Median time to transplantation for occurrence of bloodstream infection	21 (4–28)	19 (4–38)	0.231
Bloodstream infection pathogen			0.361
Klebsiella pneumoniae	1 (6.3)	8 (29.6)
Escherichia coli	2 (12.5)	5 (18.5)
Staphylococcus epidermidis	3 (18.8)	5 (18.5)
Streptococcus pyogenes	2 (12.5)	1 (3.7)
bacillus subtilis	2 (12.5)	0
Enterococcus faecalis	2 (12.5)	3 (11.1)
Pseudomonas aeruginosa	1 (6.3)	1 (3.7)
Others	3 (18.8)	4 (14.8)
Infection from engraftment to 1 year after allo-HSCT, n (%)
Overall infection, n (%)	127 (63.2)	113 (56.5)	0.172
More than one type of infection	66 (32.8)	48 (24.0)	0.050
Bacterial infection	71 (35.3)	57 (28.5)	0.143
Fungal infection	68 (33.8)	45 (22.5)	0.012
Viral infection	87 (43.3)	72 (36.0)	0.136

Table 4.

Univariate analysis of infection.

Variables	Total (n = 401)		Conventional laminar air flow room (n = 401)		Plasma sterilizer (n = 401)
Variables	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Infection
Type
Conventional laminar air flow room	1.00		NA		NA
Plasma sterilizers	1.23 (0.82–1.86)	0.324	NA	NA	NA	NA
Age
≤55 years	1.00		1.00		1.00
>55 years	1.39 (0.86–2.25)	0.174	1.25 (0.62–2.55)	0.533	1.56 (0.82–3.00)	0.179
Gender
Male	1.00		1.00		1.00
Female	0.77 (0.51–1.18)	0.235	0.87 (0.47–1.61)	0.656	0.70 (0.39–1.25)	0.224
Underlying disease
Nonmalignant hematologic disease	1.00		1.00		1.00
Hematologic malignancies	1.75 (0.64–4.76)	0.275	1.13 (0.27–4.69)	0.862	2.47 (0.60–10.17)	0.211
Chemotherapy before stem cell transplantation
No	1.00		1.00		1.00
Yes	0.87 (0.50–1.52)	0.636	1.34 (0.48–3.76)	0.577	0.72 (0.37–1.41)	0.337
Donor type
MSD	1.00		1.00		1.00
HID	0.94 (0.56–1.58)	0.808	0.79 (0.38–1.66)	0.532	1.10 (0.53–2.28)	0.797
MUD	0.84 (0.31–2.27)	0.735	0.54 (0.12–2.49)	0.427	1.30 (0.35–4.82)	0.691
Donor–recipient sex matched
Others	1.00		1.00		1.00
Female to male	1.13 (0.66–1.94)	0.649	0.57 (0.20–1.59)	0.283	1.68 (0.87–3.22)	0.120
ABO-matched graft
Matched	1.00		1.00		1.00
Mismatch	1.21 (0.80–1.83)	0.362	0.72 (0.38–1.34)	0.295	1.88 (1.06–3.33)	0.032
MNC counts
≤median	1.00		1.00		1.00
>median	0.56 (0.36–0.85)	0.007	0.77 (0.41–1.44)	0.416	0.40 (0.22–0.73)	0.002
CD34⁺ counts
≤median	1.00		1.00		1.00
>median	1.40 (0.92–2.12)	0.113	1.61 (0.85–3.02)	0.141	1.30 (0.74–2.27)	0.361
HCT-CI scores
0 (low risk)	1.00		1.00		1.00
1–2 (intermediate risk)	0.81 (0.46–1.44)	0.472	1.10 (0.53–2.27)	0.803	0.54 (0.20–1.52)	0.245
≥3 (high risk)	0.88 (0.41–1.92)	0.750	0.85 (0.33–2.22)	0.745	1.54 (0.37–6.38)	0.548
More than one type of infection
Type
Conventional laminar air flow room	1.00		NA		NA
Plasma sterilizers	1.35 (0.30–6.03)	0.694	NA	NA	NA	NA
Age
<55 years	1.00		1.00		NA
≥55 years	1.69 (0.33–8.70)	0.532	8.00 (0.73–88.26)	0.090	NA	NA
Gender
Male	1.00		NA		1.00
Female	0.21 (0.03–1.76)	0.151	NA	NA	0.43 (0.04–4.15)	0.467
Underlying disease
Nonmalignant hematologic disease	NA		NA		NA
Hematologic malignancies	NA	NA	NA	NA	NA	NA
Chemotherapy before stem cell transplantation
No	1.00		NA		1.00
Yes	1.02 (0.12–8.48)	0.985	NA	NA	0.62 (0.06–5.96)	0.679
Donor type
MSD	1.00		NA		1.00
HID	1.48 (0.18–12.30)	0.716	NA	NA	0.76 (0.08–7.33)	0.814
MUD	NA	NA	NA	NA	NA	NA
Donor–recipient sex matched
Others	1.00		1.00		NA
Female to male	2.07 (0.40–10.65)	0.386	11.64 (1.06–128.36)	0.045	NA	NA
ABO-matched graft
Matched	1.00		1.00		1.00
Mismatch	1.52 (0.34–6.79)	0.584	2.41 (0.22–26.60)	0.472	1.07 (0.15–7.62)	0.944
MNC counts
≤median	1.00		1.00		1.00
>median	1.39 (0.31–6.20)	0.668	2.60 (0.24–28.65)	0.436	0.83 (0.12–5.92)	0.856
CD34⁺ counts
≤median	1.00		1.00		1.00
>median	0.76 (0.17–3.38)	0.713	0.42 (0.04–4.63)	0.479	1.21 (0.17–8.56)	0.852
HCT-CI scores
0 (low risk)	1.00		1.00		1.00
1–2 (intermediate risk)	NA	NA	NA	NA	NA	NA
≥ 3 (high risk)	3.71 (0.72–19.10)	0.117	2.39 (0.22–26.34)	0.477	11.10 (1.15–106.71)	0.037
Bacterial infection
Type
Conventional laminar air flow room	1.00		NA		NA
Plasma sterilizers	1.22 (0.78–1.91)	0.374	NA	NA	NA	NA
Age
<55 years	1.00		1.00		1.00
≥55 years	1.50 (0.90–2.50)	0.117	1.33 (0.62–2.82)	0.463	1.71 (0.86–3.40)	0.126
Gender
Male	1.00		1.00		1.00
Female	0.87 (0.55–1.37)	0.545	1.03 (0.53–1.99)	0.926	0.75 (0.40–1.39)	0.360
Underlying disease
Nonmalignant hematologic disease	1.00		1.00		1.00
Hematologic malignancies	1.98 (0.62–6.27)	0.247	0.95 (0.23–3.97)	0.949	4.22 (0.58–30.67)	0.155
Chemotherapy before stem cell transplantation
No	1.00		1.00		1.00
Yes	1.20 (0.62–2.33)	0.587	1.56 (0.48–5.09)	0.460	1.08 (0.48–2.43)	0.857
Donor type
MSD	1.00		1.00		1.00
HID	0.97 (0.55–1.71)	0.918	0.63 (0.29–1.35)	0.231	1.51 (0.64–3.60)	0.349
MUD	0.81 (0.27–2.43)	0.703	0.54 (0.12–2.49)	0.429	1.29 (0.26–6.39)	0.755
Donor–recipient sex matched
Others	1.00		1.00		1.00
Female to male	1.17 (0.66–2.09)	0.592	0.69 (0.24–1.94)	0.477	1.62 (0.80–3.29)	0.184
ABO–matched graft
Matched	1.00		1.00		1.00
Mismatch	1.30 (0.84–2.03)	0.243	0.84 (0.43–1.63)	0.602	1.89 (1.01–3.53)	0.045
MNC counts
≤median	1.00		1.00		1.00
>median	0.46 (0.29–0.74)	0.001	0.62 (0.31–1.24)	0.178	0.34 (0.18–0.66)	0.001
CD34⁺ counts
≤median	1.00		1.00		1.00
>median	1.34 (0.86–2.10)	0.199	1.56 (0.79–3.08)	0.198	1.23 (0.67–2.25)	0.502
HCT-CI scores
0 (low risk)	1.00		1.00		1.00
1–2 (intermediate risk)	0.73 (0.38–1.38)	0.330	1.04 (0.46–2.32)	0.931	0.45 (0.14–1.47)	0.186
≥ 3 (high risk)	0.87 (0.38–2.01)	0.746	1.02 (0.39–2.68)	0.971	0.85 (0.12–6.19)	0.873
Fungal infection
Type	NA	NA
conventional laminar air flow room	1.00		NA		NA
plasma sterilizers	2.02 (0.18–22.28)	0.566	NA	NA	NA	NA
Age
<55 years	NA		NA		NA
≥55 years	NA	NA	NA	NA	NA	NA
Gender
Male	1.00		NA		1.00
Female	0.64 (0.06–7.07)	0.716	NA	NA	1.31 (0.08–20.89)	0.850
Underlying disease
Nonmalignant hematologic disease	NA		NA		NA
Hematologic malignancies	NA	NA	NA	NA	NA	NA
Chemotherapy before stem cell transplantation
No	1.00		NA		NA
Yes	0.08 (0.01–0.92)	0.042	NA	NA	NA	NA
Donor type
MSD	1.00		NA		1.00
HID	0.24 (0.02–3.90)	0.318	NA		NA	NA
MUD	3.03 (0.19–48.41)	0.433	NA	NA	3.62 (0.23–57.97)	0.363
Donor–recipient sex matched
Others	NA		NA		NA
Female to male	NA	NA	NA	NA	NA	NA
ABO-matched graft
Matched	1.00		NA		NA
Mismatch	2.30 (0.21–25.38)	0.496	NA	NA	NA	NA
MNC counts
≤median	1.00		NA		1.00
>median	0.52 (0.05–5.72)	0.592	NA	NA	0.84 (0.05–13.41)	0.901
CD34⁺ counts
≤median	1.00		NA		1.00
>median	0.50 (0.05–5.55)	0.575	NA	NA	1.20 (0.08–19.26)	0.895
HCT-CI scores
0 (low risk)	1.00		NA		1.00
1–2 (intermediate risk)	NA	NA	NA		NA	NA
≥3 (high risk)	4.70 (0.43–51.78)	0.207	NA	NA	33.50 (2.10–535.58)	0.013

CI: Confidence interval; HR: Hazard ratio; HCT-CI: Hematopoietic cell transplantation–comorbidity index; MSD: Matched sibling donor; HID: Haploidentical donor; MUD: Matched unrelated donor; NA: Not applicable.

Table 5.

Multivariate analysis of infection.

Variables	Total (n = 401)		Conventional laminar air flow room (n = 401)		Plasma sterilizer (n = 401)
Variables	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Infection
ABO-matched graft
Matched					1.00
Mismatch					1.83 (1.03–3.25)	0.039
MNC counts
≤median	1.00				1.00
>median	0.52 (0.34–0.80)	0.003			0.41 (0.23–0.74)	0.003
More than one type of infection
Donor–recipient sex matched
Others			1.00
Female to male			12.45 (1.13–137.62)	0.040
HCT-CI scores
0 (low risk)					1.00
1–2 (intermediate risk)					NA	NA
≥3 (high risk)					11.10 (1.15–106.71)	0.037
Bacterial infection
MNC counts
≤median	1.00				1.00
>median	0.43 (0.26–0.69)	<0.001			0.35 (0.18–0.66)	0.001
Fungal infection
Chemotherapy before stem cell transplantation
No	1.00
Yes	0.08 (0.01–0.92)	0.042
HCT-CI scores
0 (low risk)					1.00
1–2 (intermediate risk)					NA	NA
≥3 (high risk)					33.50 (2.10–535.58)	0.013

During the period from engraftment to 1 year after allo-HSCT, the rates of overall infection, more than one type of infection, bacterial infection and viral infection were comparable between the two groups, and patients in the plasma sterilizer group exhibited a lower rate of fungal infection (Table 3).

Engraftment, GVHD, relapse, and non-relapse mortality

Within 100 days after allo-HSCT, there was no statistically significant difference observed between the two groups in terms of neutrophil engraftment, platelet engraftment (Table 1). The clinical outcomes were also comparable in terms of the probability of OS (98.5% [95% CI: 86.8%–100%] vs 99.5% [95% CI: 98.5%–100%]; P = 0.316), probability of LFS (96.5% [95% CI: 94.0%–99.0%] vs 96.5% [95% CI: 94.0%–99.1%]; P = 0.991), the cumulative incidence of relapse (2.0% [95% CI: 0.1%–3.9%] vs 3.0% [95% CI: 0.6%–5.4%]; P = 0.523), the cumulative incidence of NRM (1.5% [95% CI: 0%–3.2%] vs 0.5% [95% CI: 0%–1.5%]; P = 0.316) and 100-day cumulative incidence of acute graft-versus-host disease (23.4% [95% CI: 17.5%–29.3%] vs 22.0% [95% CI: 16.2%–27.8%], P = 0.723) respectively, for conventional laminar flow room group and plasma sterilizer group (Fig. 2).

Figure 2.

100-day clinical outcomes after allo-HSCT. (a) OS. (b) LFS. (c) Relapse. (d) NRM. (e) Acute GVHD.

At the 1-year follow-up after allo-HSCT, the probability of OS was 98.5% (95% CI: 96.8%–100%) for the plasma sterilizer group, which was better than that of the conventional laminar flow room group (91.5%; 95% CI: 87.6%–95.4%; P = 0.005). Patients in the plasma sterilizer group also exhibited a better 1-year probability of LFS (94.0% [95% CI: 97.3%–100%] vs 85.9% [95% CI: 81.2%–90.9%]; P = 0.010) and a lower 1-year cumulative incidence of NRM after allo-HSCT (1.0% [95% CI: 0%–2.4%] vs 8.6% [95% CI: 4.7%–12.5%]; P = 0.00047). The 1-year cumulative incidence of relapse (5.0% [95% CI: 1.9%–8.1%] vs 5.5% [95% CI: 2.3%–8.7%]; P = 0.851) and the 1-year cumulative incidence of chronic GVHD (36.5% [95% CI: 29.8%–43.2%] vs 30.8% [95% CI: 24.4%–37.2%]; P = 0.233) after allo-HSCT were comparable between the plasma sterilizer group and the conventional laminar flow room group (Fig. 3).

Figure 3.

1-year clinical outcomes after allo-HSCT. (a) OS. (b) LFS. (c) Relapse. (d) NRM. (e) Chronic GVHD.

Discussion

In this study, we observed that there were no significant differences in infection rates, engraftment rates, or 100-day posttransplantation clinical outcomes between the plasma sterilizer and conventional laminar flow rooms. At the 1-year follow-up after allo-HSCT, the laminar flow room group demonstrated superior OS and LFS, as well as a lower NRM. This is the first study reporting that allogeneic hematopoietic stem cell transplantation conducted in a plasma sterilizer environment can achieve clinical outcomes similar to those of transplantation conducted in a conventional laminar flow room. As our institution is the first in China to adopt plasma sterilizers on a large scale for allo-HSCT, the findings may serve as evidence for the potential broader implementation of plasma sterilizers in hematopoietic stem cell transplantation centers.

According to the operating instructions for both devices, conventional laminar flow rooms reduce airborne particles and pathogenic microorganisms to safe levels via primary, intermediate, and high-efficiency filters. Plasma sterilizers result in airborne pathogenic microorganisms and particles being maintained at safe standards via discharge, dissociation, and high-efficiency particulate air (HEPA) filtration. Laminar flow purification via air ventilation systems is often considered to be the safest and most effective measure for preventing respiratory infections in hematology/oncology wards. The effectiveness of HEPA in reducing the number of ambient fungal spores has been demonstrated in several studies; for example, via plasma sterilizers, the number of ambient fungal spores was reduced by 86% compared with the number of surface fungi in normal rooms, and airborne filamentous fungi were reduced by 80%. However, these fungi were not completely removed, and the monitored airborne filamentous fungi concentration was still observed at 3.2 ± 2.8 CFU/m³, which could be improved by increasing the air volume for better air purification¹⁹. In contrast, in our current study, repeated monitoring at multiple time points revealed that the number of pathogenic microorganisms in the plasma sterilizer group was <5 planktonic bacteria/m³, the number of settled bacteria was <1/Φ90 dish-30 min, the number of particles <0.5 µm in dust was less than 3,500 particles/m³, and the number of dust particles ≥5 µm was 0. Moreover, the rate of lung infections, the time of occurrence and the number of pathogens in patients who received allo-HSCT in the environment of the plasma sterilizer were similar to those of patients who received allo-HSCT in conventional laminar flow rooms, which also suggests that the sterile environment provided by the plasma sterilizer can effectively prevent lung infections during the granulocyte-deficient phase in allogeneic transplantation patients.

In accordance with previous domestic and international research, immunocompromised patients in the plasma sterilizer environment can be effectively protected from infections. For example, some studies have confirmed that this type of purification system can effectively reduce the occurrence of Aspergillus infections. Among hematology patients in the neutropenia stage, the infection incidence rate in the plasma sterilizer environment was observed to be 1.15%, which was significantly lower than that of patients in general wards (14.49%, P = 0.02; odds ratio (OR): 0.11; 95% CI: 0.00–0.84). They also reported a positive association between Aspergillus infection and the use of a plasma sterilizer (P = 0.03)²⁰. Similarly, some authors have demonstrated that plasma sterilizers are more effective in infection prophylaxis than conventional air purification systems in burn wards. Specifically, before and after operation of the sterilizers, the use of plasma wards resulted in a significant decrease in the number of suspended particles in the air, thereby reducing the occurrence of infection²¹. Allogeneic hematopoietic stem cell transplantation recipients represent the population of patients with severe immunodeficiencies, and our study demonstrated that plasma sterilizers are effective in infection prophylaxis in preengraftment patients.

For patients receiving allo-HSCT in conventional laminar flow rooms, the rates of lung infections, catheter-associated bloodstream infections, and bloodstream infections have been demonstrated to be 18.4% to 85.48%^22–24, 2.8% to 11.2%²⁵, and 10% to 50%^26–28, respectively, during the preengraftment phase. In our present study, the rates of lung infections, catheter-associated bloodstream infections, and bloodstream infections were 8%, 13.5%, and 13.5%, respectively, during the preengraftment phase for patients receiving allo-HSCT via the plasma sterilizer. Therefore, our results suggested that the efficacy of infection prevention was comparable between plasma sterilizer and conventional laminar flow rooms.

However, the difference in the timing of enrollment between the two groups (a 12-month gap, with the patients in the conventional laminar flow room group being enrolled in 2022, whereas those in the laminar flow room group were enrolled in 2023) may have contributed to the observed differences in long-term outcomes. The changing epidemiology of COVID-19 in China^29–31, which was driven by evolving government policies and vaccination efforts, led to differences in infection rates between 2022 and 2023, which may have contributed to variations in NRM during long-term follow-up. Given the multitude of factors affecting long-term prognosis, the direct impact of laminar flow rooms on extended outcomes requires further investigation.

There were several limitations in this study. For example, this was a single-center, retrospective study, which may limit the generalizability of our findings. Some patients developed symptoms such as fever and received symptomatic antiinfection treatments; however, the pathogens were not identified, which may interfere with the statistical results regarding infections. Notably, many factors can influence infections, and the differences observed in laminar flow rooms may only represent one aspect of the impact on infection occurrence in both short-term and long-term follow-ups, which could be confounded by other factors.

In conclusion, our results suggest that the conventional laminar flow room remains the cornerstone of patient treatment, whereas a plasma sterilizer may also be used to improve patient outcomes. These results should be confirmed via multicenter, randomized controlled trials in the future.

Supplemental Material

sj-docx-1-cll-10.1177_09636897251335722 – Supplemental material for Comparison of plasma sterilizer and conventional laminar flow room in allogeneic hematopoietic stem cell transplant recipients

Supplemental material, sj-docx-1-cll-10.1177_09636897251335722 for Comparison of plasma sterilizer and conventional laminar flow room in allogeneic hematopoietic stem cell transplant recipients by Ting Wang, Yi Xia, Wei Hu, Boning Liu, Xiaohui Zhang, Wenxuan Huo, Jun Kong, Yaru Ma, Wenwen Xiao, Ce Shi, Qixin Du, Leqing Cao, Dong Han, Dongyue Yao, Hongyue Yin, Daoxing Deng, Jingyu Gao, Yashu Jia, Jiating Wang, Jing Liu, Xiaoshuang Han, Junxia Wang, Ling Ma, Yunjing Xia, Shanshan Hu, Yuanyuan Zhang, Fengmei Zheng, Xiaojun Huang and Xiaodong Mo in Cell Transplantation

Footnotes

ORCID iDs

Ting Wang

Yi Xia

Ethical considerations

The study was approved by the institutional review board of Peking University People’s Hospital (No. 2025PHB085-001) and was conducted in accordance with the Declaration of Helsinki.

Author contributions

T.W. and Y.X. analyzed the data and wrote the manuscript; W.H. and B.N.L. contributed to the data collection and helped write and edit the manuscript. W.X.H. performed statistical analysis; X.J.H., X.H.Z., and X.D.M. designed the study, analyzed the data, and edited the manuscript.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Science Foundation of Beijing (Z230016) and the National Key Research and Development Program of China (2022YFA1103300, 2022YFC2502606).

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Statement of human and animal rights

This article does not contain any studies with human or animal subjects.

Statement of informed consent

There are no human subjects in this article and informed consent is not applicable.

Data Availability Statement

The data set supporting the conclusions of this article is available in the clinical data repository of our affiliation. Individual participant data were not shared. For the original data, please contact the corresponding author.

Supplemental material

Supplemental material for this article is available online.

References

Wang

Zhang

Fan

. Treatment options for adult intermediate-risk AML patients in CR1: allo-HSCT or chemotherapy? Innovation (Camb). 2023;4(4):100461.

Wang

Liu

Chang

Zhang

Cao

Liu

Wang

, et al. Allogeneic versus autologous hematopoietic stem cell transplantation for adult T-lymphoblastic lymphoma: A real-world multicenter analysis in China. Cancer Lett. 2025;621:217664.

Zhao

Guo

Chang

. MRD-directed and risk-adapted individualized stratified treatment of AML. Chin J Cancer Res. 2023;35(5):451–69.

Jiang

Zhao

Luo

Chen

Lai

Liu

Zheng

, et al. Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors. Cell Transplant. 2024;33.

Zhao

Chen

Pei

Zhang

Shi

Huang

Zhao

. TP53 in MDS and AML: Biological and clinical advances. Cancer Lett. 2024;588:216767.

Sun

Wang

Zhang

Liu

Yan

Liu

Huang

. Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation. Ann Hematol. 2019;98(8):1877–83.

Dominietto

Raiola

Van Lint

Lamparelli

Gualandi

Berisso

Bregante

Frassoni

Casarino

Verdiani

Bacigalupo

. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001;112(1):219–27.

Wang

Gao

Wang

Zhang

Wang

Yan

Chen

Han

Wang

, et al. Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs. identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia. Chin J Cancer Res. 2024;36(5):530–44.

Luo

Pei

Zhang

Chen

. Targeting early EBV-driven IDO1-NAD metabolism as a potential therapeutic strategy for EBV-related diseases. The Innovation Medicine. 2024;2(3):100084.

10.

Wang

Zhang

Cao

Shao

Liu

. Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation. Chin J Cancer Res. 2023;35(4):386–98.

11.

Jiang

Zhang

Wang

Yan

Chen

Han

Wang

Sun

, et al. Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation. Cell Transplant. 2024;33.

12.

Liu

Cao

. Vedolizumab provides a new hope of acute graft-versus-host disease prophylaxis through immune regulation. Innov Med. 2024;2(3):100083.

13.

Zhang

Wang

Jing

Gao

Dou

, et al. Similar Survival But Less Chronic GVHD in Antithymocyte Globulin-Based Myeloablative Haploidentical Transplant Compared With Matched Sibling Transplant for Adult T-cell Acute Lymphoblastic Leukemia/Lymphoma. Cell Transplant. 2024;33.

14.

Wang

Chang

Chen

Han

Huang

Lai

Liu

Luo

, et al. Consensus on the monitoring, treatment, and prevention of leukaemia relapse after allogeneic haematopoietic stem cell transplantation in China: 2024. Cancer Lett. 2024;605:217264.

15.

Zheng

. Effect of class 10000 laminar flow ward on the incidence of healthcare-associated infection inpatients with initial occurrence of acute leukemiaduring induction chemotherapy period. Chin J Infect Control. 2016;15(04):250–53.

16.

Hahn

Cummings

Michalek

Lipman

Segal

McCarthy

Jr.

Efficacy of high-efficiency particulate air filtration in preventing aspergillosis in immunocompromised patients with hematologic malignancies. Infect Control Hosp Epidemiol. 2002;23(9):525–31.

17.

Poirot

Gangneux

Fischer

Malbernard

Challier

Laudinet

Bergeron

. Evaluation of a new mobile system for protecting immune-suppressed patients against airborne contamination. Am J Infect Control. 2007;35(7):460–66.

18.

Sixt

Dalle

Lafon

Aho

Couillault

Valot

Calinon

Danaire

Vagner

Cuisenier

Sautour

, et al. Reduced fungal contamination of the indoor environment with the Plasmair system (Airinspace). J Hosp Infect. 2007;65(2):156–62.

19.

Brenier-Pinchart

Coussa-Rivière

Lebeau

Mallaret

Bulabois

Ducki

Cahn

Grillot

Pelloux

. Mobile air-decontamination unit and filamentous fungal load in the hematology ward: how efficient at the low-activity mode? Am J Infect Control. 2009;37(8):680–82.

20.

Fernandez-Gerlinger

Jannot

Rigaudeau

Lambert

Eloy

Mignon

Farhat

Castaigne

Merrer

Rousselot

. The Plasmair decontamination system is protective against invasive aspergillosis in neutropenic patients. Infect Control Hosp Epidemiol. 2016;37(7):845–51.

21.

Sakudo

Yamashiro

Onodera

. Recent Advances in Prion Inactivation by Plasma Sterilizer. Int J Mol Sci. 2022;23(18).

22.

Feng

Zhang

Qiu

. Clinical Features of Infection within 100 days after Hematopoietic Stem Cell Transplantation in 313 patients with Hematologic Diseases. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020;28(2):602–608.

23.

Russo

Mendes

Levin

Dulley

Oliveira

Shikanai-Yasuda

Costa

. Bloodstream infection in hematopoietic stem cell transplantation outpatients: risk factors for hospitalization and death. Rev Inst Med Trop Sao Paulo. 2018;61:e3.

24.

Chen

Liu

Zhang

. Risk factors for postoperative pulmonary infection after allogeneic hematopoietic stem cell transplantation. Chin J Lab Diagn. 2017;21(12):2125–29.

25.

Wang

Tong

. Research progress on risk factors for intravascular catheter-related bloodstream infection. J Clin Nurs. 2019;18(01):60–64.

26.

Almyroudis

Fuller

Jakubowski

Sepkowitz

Jaffe

Small

Kiehn

Pamer

Papanicolaou

. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2005;7(1):11–17.

27.

Ortega

Rovira

Almela

Marco

de la Bellacasa

Martínez

Carreras

Mensa

. Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol. 2005;84(1):40–46.

28.

Blennow

Ljungman

Sparrelid

Mattsson

Remberger

. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis. 2014;16(1):106–14.

29.

Huang

Gao

Wang

. China's COVID-19 reopening measures-warriors and weapons. Lancet. 2023;401(10377):643–44.

30.

Zhou

Lai

Tang

Liu

Shen

Peng

. Estimating cumulative infection rate of COVID-19 after adjusting the dynamic zero-COVID policy in China. Infect Dis Model. 2025;10(2):429–38.

31.

Chen

Gong

Chen

Liu

Sun

Yang

Chen

. Features and significance of the recent enormous COVID-19 epidemic in China. J Med Virol. 2023;95(3):e28616.

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