异基因造血干细胞移植后晚发重症肺炎患者治疗与预后转归的关系

doi:10.19723/j.issn.1671-167X.2022.05.031

Abstract

Abstract:

Objective: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). Methods: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. Results: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. Conclusion: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.

Key words: Allogeneic hematopoietic stem cell transplantation, Pneumonia, Antiviral agents, Glucocorticoids, Prognosis

CLC Number:

R733

Le-qing CAO,Jing-rui ZHOU,Yu-hong CHEN,Huan CHEN,Wei HAN,Yao CHEN,Yuan-yuan ZHANG,Chen-hua YAN,Yi-fei CHENG,Xiao-dong MO,Hai-xia FU,Ting-ting HAN,Meng LV,Jun KONG,Yu-qian SUN,Yu WANG,Lan-ping XU,Xiao-hui ZHANG,Xiao-jun HUANG. Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation[J].Journal of Peking University (Health Sciences), 2022, 54(5): 1013-1020.

Figures/Tables 4

Table 1

Comparison of clinical characteristics of patients with LOSP after allogeneic hematopoietic stem cell transplantation"

Characteristics	Total	Outcomes at 60 d		P value
Characteristics	Total	Survival	Death	P value
Patients (male/female), n	82 (57/25)	48 (32/16)	34 (25/9)	0.506
Age/years, M (Range)	36 (12-66)	41 (12-66)	35 (17-64)	0.446
Diagnosis, n(%)				0.859
AML	30 (36.6)	16 (33.3)	14 (41.2)
ALL	34 (41.5)	21 (43.8)	13 (38.2)
MDS	9 (11.0)	6 (12.5)	3 (8.8)
Others	9 (11.0)	5 (10.4)	4 (11.8)
Transplant type, n(%)				0.599
MSDT	17 (20.7)	9 (18.8)	8 (23.5)
Haplo-SCT	65 (79.3)	39 (81.3)	26 (76.5)
Engraftment, n(%)
Neutrophil	82 (100)	48 (100)	34 (100)
Platelet	77 (93.9)	47 (97.9)	30 (88.2)	0.071
Time to engraftment/d, M (Range)
Neutrophil	14 (10-23)	13 (10-23)	14 (11-23)	0.084
Platelet	15 (8-180)	15 (8-180)	18 (9-117)	0.281
Early complications after transplantation, n(%)
Cytomegalovirus viremia	55 (67.1)	32 (66.7)	23 (67.6)	0.926
EBV infection	14 (17.1)	7 (14.6)	7 (20.6)	0.476
Acute GVHD Ⅱ-Ⅳ	16 (19.5)	11 (22.9)	5 (14.7)	0.198
Acute GVHD Ⅲ-Ⅳ	8 (9.8)	4 (8.3)	4 (11.8)	0.465
Chronic GVHD	43 (52.4)	27 (56.1)	16 (47.1)	0.580
Time of LOSP post-transplantation/d, M (Range)	220 (93-813)	224 (98-811)	215 (96-813)	0.421
Season of LOSP, n(%)				0.042
Spring (March to May)	14 (17.1)	10 (20.8)	4 (11.8)
Summer (June to August)	19 (23.2)	6 (12.5)	13 (38.2)
Autumn (September to November)	22 (26.8)	13 (27.1)	9 (26.5)
Winter (December to February of the following year)	27 (32.9)	19 (39.6)	8 (23.5)
Pathogens detected during LOSP, n(%)				0.706
Virus	31 (37.8)	19 (39.6)	12 (35.3)
Bacteria	4 (4.9)	2 (4.2)	2 (5.9)
Fungus	1 (1.2)	1 (2.1)	0
Mixed organisms (virus+bacteria/fungus)	7 (8.5)	5 (10.4)	2 (5.9)
Unidentified	39 (47.6)	21 (43.8)	18 (52.9)
Time from the start of intravenous antibacterial drugs to the onset of respiratory symptoms/d, M (Range)	0 (0-14)	0 (0-12)	0 (0-14)	0.545
Treatment with antiviral drugs, n(%)	80 (97.6)	47 (97.9)	33 (97.1)	0.804
Time from antiviral drug initiation to onset of LOSP/d, M (Range)	5 (0-27)	5 (0-20)	7 (0-22)	0.386
Time from antiviral drug initiation to onset of LOSP, n(%)				0.014
< 10 d	60 (75.0)	40 (85.1)	20 (60.6)
≥ 10 d	20 (25.0)	7 (14.9)	13 (39.4)
Major antiviral drugs ^*, n(%)				0.501
Ganciclovir	19 (23.8)	13 (27.7)	6 (18.2)
Acyclovir	10 (12.5)	4 (8.5)	6 (18.2)
Foscarnet sodium	38 (47.5)	23 (48.9)	15 (45.5)
Combination	13 (16.3)	7 (14.9)	6 (18.2)
Glucocorticoid treatment during LOSP, n(%)	73 (89.0)	41 (85.4)	32 (94.1)	0.214
Time from LOSP onset to glucocorticoid use/d, M (Range)	10 (0-41)	13 (1-41)	10 (0-31)	0.084
Time from glucocorticoid initiation to antiviral drug/d, M (Range)	4 (0-35)	5 (0-35)	2 (0-14)	0.029
Time from glucocorticoid initiation to antiviral drug, n(%)				0.011
< 10 d	58 (80.6)	28 (70.0)	30 (93.8)
≥ 10 d	14 (19.4)	12 (30.0)	2 (6.3)
Type of mechanical ventilation, n(%)
Non-invasive mechanical ventilation	30 (36.6)	11 (22.9)	19 (55.9)	0.002
Invasive mechanical ventilation	25 (30.5)	3 (6.3)	22 (64.7)	＜0.001

Table 1

Table 2

Figure 1

Table 3

Comparison of clinical characteristics between groups of patients with LOSP after allogeneic hematopoietic stem cell transplantation"

Characteristics	Time from antiviral drug initiation to onset of LOSP			Time from glucocorticoid initiation to antiviral drug
Characteristics	< 10 d	≥ 10 d	P value	< 10 d	≥ 10 d	P value
Patients (male/female), n	60 (40/20)	20 (15/5)	0.486	58 (43/15)	14 (8/6)	0.209
Age/years, M (Range)	41 (12-66)	32 (19-64)	0.100	36 (12-66)	45 (21-58)	0.385
Diagnosis, n(%)			0.816			0.305
AML	24 (40.0)	6 (30.0)		20 (34.5)	8 (57.1)
ALL	23 (38.3)	9 (45.0)		25 (43.1)	3 (21.4)
MDS	7 (11.7)	2 (10.0)		5 (8.6)	2 (14.3)
Others	6 (10.0)	3 (15.0)		8 (13.8)	1 (7.1)
Transplant type, n(%)			> 0.999			0.524
MSDT	12 (20.0)	4 (20.0)		12 (20.7)	4 (28.6)
Haplo-SCT	48 (80.0)	16 (80.0)		46 (79.3)	10 (71.4)
Engraftment, n(%)
Neutrophil	60 (100.0)	20 (100.0)		58 (100.0)	14 (100.0)
Platelet	57 (95.0)	18 (90.0)	0.424	54 (93.1)	14 (100.0)	0.312
Time to engraftment/d, M (Range)
Neutrophil	14 (10-23)	14 (11-23)	0.871	14 (11-23)	13 (10-23)	0.235
Platelet	15 (8-180)	18 (10-46)	0.606	15 (9-180)	14 (8-38)	0.155
Early complications after transplantation, n(%)
Cytomegalovirus viremia	40 (66.7)	14 (70.0)	0.783	40 (69.0)	7 (50.0)	0.181
EBV infection	9 (15.0)	4 (20.0)	0.600	8 (13.8)	2 (14.3)	0.962
Acute GVHD Ⅱ-Ⅳ	12 (20.0)	4 (20.0)	> 0.999	9 (15.5)	5 (35.7)	0.087
Acute GVHD Ⅲ-Ⅳ	4 (6.7)	4 (20.0)	0.085	5 (8.6)	3 (21.4)	0.171
Chronic GVHD	29 (48.3)	13 (60.0)	0.285	30 (51.7)	9 (64.3)	0.335
Time of LOSP post-transplantation/d, M (Range)	222 (96-813)	222 (93-623)	0.537	215 (96-813)	233 (110-811)	0.490
Pathogens detected during LOSP, n(%)			0.530			0.841
Virus	24 (40.0)	5 (25.0)		20 (34.5)	5 (35.7)
Bacteria	3 (5.0)	2 (10.0)		4 (6.9)	0
Fungus	1 (1.7)	0		1 (1.7)	0
Mixed organisms (virus+bacteria/fungus)	6 (10.0)	1 (5.0)		5 (8.6)	1 (7.1)
Unidentified	26 (43.3)	12 (60.0)		28 (48.3)	8 (57.1)
Time from the start of intravenous antibiotics to the onset of respiratory symptoms/d, M (Range)	0 (0-10)	0 (0-14)	0.552	0 (0-14)	0 (0-14)	0.364
Major antiviral drugs ^*, n(%)			0.423			0.314
Ganciclovir	17 (28.3)	2 (10.0)		13 (22.4)	3 (21.4)
Acyclovir	7 (11.7)	3 (15.0)		10 (17.2)	0
Foscarnet sodium	27 (45.0)	11 (55.0)		25 (43.1)	9 (64.3)
Combination	9 (15.0)	4 (20.0)		10 (17.2)	2 (14.3)
Type of mechanical ventilation, n(%)
Non-invasive mechanical ventilation	24 (40.0)	6 (30.0)	0.424	25 (43.1)	4 (28.6)	0.320
Invasive mechanical ventilation	16 (26.7)	9 (45.0)	0.126	23 (39.7)	1 (7.1)	0.021

Table 3

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Characteristics	Univariate analysis			Multivariate analysis
Characteristics	χ² value/Z value	P value	OR value	95%CI	P value
Platelet engraftment (yes or no)	3.258	0.071
Engraftment time of neutrophil	-1.728	0.084
Time from antiviral drug initiation to onset of LOSP (< 10 d vs. ≥ 10 d)	6.207	0.014	0.183	0.048-0.693	0.012
Time from glucocorticoid initiation to onset of LOSP (< 7 d vs. ≥ 7 d)	2.924	0.087
Time from glucocorticoid initiation to antiviral drug (< 10 d vs. ≥ 10 d)	6.402	0.011	6.503	1.235-34.238	0.027

Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation

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