Assessing the significance of cytomegalovirus reactivation in recipients of allogeneic hematopoietic stem cell transplantation: a cohort study

Oliveira, L.P. de; Paton, E.J.A.; Giovanardi, M.F.; Silva, A.F. da; Tavares, L.G.; Fernandes, C.G.; Dias, J.O.; Fabreti-Oliveira, R.A.

doi:10.1590/1414-431X2026e15073

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Research Article • Braz. J. Med. Biol. Res. 59 • 2026 • https://doi.org/10.1590/1414-431X2026e15073 linkcopy

Assessing the significance of cytomegalovirus reactivation in recipients of allogeneic hematopoietic stem cell transplantation: a cohort study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Cytomegalovirus (CMV) infection increases morbidity in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Despite advancements in prevention and treatment, CMV reactivation remains a considerable concern following allo-HSCT. In this study, we aimed to evaluate the impact of CMV reactivation in allo-HSCT recipients on clinical outcomes and patient survival, as well as to identify the risk factors associated with CMV reactivation. This retrospective observational cohort study included data from 67 transplantations performed between 2019 and 2022 at a private hospital in Belo Horizonte, Brazil. Clinical, laboratory, and procedural data were collected. The median age of the patients was 47.0 years, and 52.2% of them were women. The most frequent indication for allo-HSCT was acute myeloid leukemia (28.4%), followed by myelodysplastic syndrome (16.4%). CMV reactivation occurred in 62.7% of the recipients, and the median time to CMV reactivation was 32.5 days. Six patients (9.0%) presented with CMV end-organ disease (83.3% were free of systemic disease); however, when present, gastrointestinal involvement was the most common disease (4.5%). In the multivariate analysis, the risk factors for CMV reactivation included acute lymphoblastic leukemia (P=0.006), mismatched human leukocyte antigen (HLA)-unrelated donors (P=0.002), and graft-versus-host disease (P=0.024). One-year overall survival was 57.7%. However, CMV reactivation was not significantly associated with mortality after controlling for confounding factors. CMV reactivation remains a common complication following allo-HSCT, with leukemia type, donor type, and graft-versus-host disease affecting the risk of disease recurrence. No direct correlation was observed between CMV recurrence and increased mortality or patient survival.

Key words:
Cytomegalovirus; Hematopoietic stem cell transplantation; Allogenic transplantation; HLA incompatibilities; Risk factor

Variables	N	Statistics
Time between diagnosis and transplant (months)	67
Min/max		1.2/385.9
Median [Q1; Q3]		10.0 [6.3; 18.5]
Mean (SD)		24.6 (51.3)
Underlying disease	67
AML		19 (28.4%)
Stage	19
Total remission		16 (84.2%)
Partial remission		2 (10.5%)
No remission - active disease		1 (5.3%)
Myelodysplastic syndrome		11 (16.4%)
Stage	11
Low risk		1 (9.1%)
Intermediate risk		2 (18.2%)
High risk		3 (27.3%)
Unclassified		5 (45.5%)
ALL		12 (17.9%)
Stage	12
Total remission		11 (91.7%)
Partial remission		1 (8.3%)
Non-neoplastic diseases^†		7 (10.4%)
Stage	7
Unclassified stage		7 (100.0%)
Myelofibrosis		5 (7.5%)
Stage	5
Progressive disease		5 (100.0%)
Hodgkin's lymphoma		4 (4.8%)
Stage	4
Complete response		1 (25.0%)
Partial response		3 (75.0%)
Others		9 (10.8%)
Unclassified stage	9	9 (100.0)
Comorbidities^‡	67	33 (50.7%)
Hypothyroidism		12 (17.9%)
Hypertension		10 (14.9%)
Others^§		24 (35.8%)
Type of donor	67
MMR		25 (37.3%)
MRD		29 (43.3%)
MMUD		1 (1.5%)
MUD		12 (17.9%)
Transplant conditioning regimen	67
Myeloablative		42 (62.7%)
Non-myeloablative		25 (37.3%)
Stem cell source	67
Bone marrow		13 (19.4%)
Peripheral blood		54 (80.6%)
Presence of GVHD^‡	67	42 (62.7%)
Acute disease	42	36 (85.7%)
Mild		15 (41.7%)
Severe		10 (27.8%)
Unclassified		11 (30.6%)
Chronic disease	42	13 (31.0%)
Mild		7 (53.8%)
Severe		2 (15.4%)
Unclassified		4 (30.8%)
Use of corticosteroids for GVHD treatment	67	31 (46.3%)
GVHD prophylaxis regimen^†
Calcineurin inhibitors + Methotrexate	67	4 (6.0%)
ATG + calcineurin inhibitors + methotrexate	67	37 (55.2%)
Post-cyclophosphamide + calcineurin inhibitors + mycophenolate	67	23 (34.3%)
ATG + post-cyclophosphamide + calcineurin inhibitors + mycophenolate	67	2 (3.0%)
Post-cyclophosphamide + calcineurin inhibitors	67	1 (1.5%)
Relapse	67	17 (25.4%)
Time between transplantation and relapse (months)	17
Min/max		1/33
Median [Q1; Q3]		6.0 [2.0; 9.0]
Mean (SD)		7.6 (8.2)
Bone marrow engraftment	67	62 (92.5%)
Time to bone marrow engraftment (days)	62
Min/max		10.0/46.0
Median [Q1; Q3]		14.0 [13.0; 17.8]
Mean (SD)		15.9 (5.7)
Follow-up time (months)	67
Min/max		0/42.0
Median [Q1; Q3]		13.0 [3.5; 22.5]
Mean (SD)		14.8 (12.2)

Variables	N	Statistics
CMV serology	67
D-/R+		10 (14.9%)
D+/R-		2 (3.0%)
D+/R+		55 (82.1%)
CMV Reactivation	67	42 (62.7%)
Time of CMV reactivation post-transplant (days)	42
Min/max		11.0/261.0
Median [Q1; Q3]		32.5 [26.2; 40.8]
Mean (SD)		41.1 (38.9)
Treatment	67
Ganciclovir		40 (59.7%)
Valganciclovir		6 (9.0%)
Clinical CMV disease	67
Absent		61 (91.0%)
GI tract involvement		3 (4.5%)
Respiratory tract involvement		2 (3.0%)
Other		1 (1.5%)
CMV pneumonitis and hepatitis		1 (100.0%)
Preemptive CMV treatment response	42	37 (88.1%)

Variable	CMV reactivation		P
	No (n=25)	Yes (n=42)
Transplant conditioning regimen			0.383
Myeloablative	14 (33.3%)	28 (66.7%)
Non-myeloablative	11 (44.0%)	14 (56.0%)
Type of allogeneic transplantation			0.709
MMR	8 (32.0%)	17 (68.0%)
MRD	11 (37.9%)	18 (62.1%)
MMUD	0 (-)	1 (100.0%)
MUD	6 (50.0%)	6 (50.0%)
GVHD prophylaxis regimen^†
Calcineurin inhibitors + methotrexate	2 (50.0%)	2 (50.0%)	0.626
ATG + calcineurin inhibitors + methotrexate	15 (40.5%)	22 (59.5%)	0.544
Post-cyclophosphamide + calcineurin inhibitors + mycophenolate	7 (30.4%)	16 (69.6%)	0.400
ATG + post-cyclophosphamide + calcineurin inhibitors + mycophenolate	1 (50.0%)	1 (50.0%)	1.000
Post-cyclophosphamide + calcineurin inhibitors	0 (-)	1 (100.0%)	1.000

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[TFN01t01] ^†Non-neoplastic diseases are sickle cell disease (n=1) and marrow aplasia (n=7). ^‡Multiple responses are possible. ^§Other comorbidities with more than one citation: depression (n=4), obesity (n=4), splenectomized (n=3), deep vein thrombosis (n=3), breast cancer (n=3), smoking (n=3), alcoholism (n=2), chronic obstructive pulmonary disease (n=2), previous pulmonary aspergillosis (n=2), hypercholesterolemia (=2). Q1: first quartile; Q3: third quartile; SD: standard deviation; AML: acute myeloid leukemia; ALL: acute lymphoblastic leukemia; ATG: anti-thymocyte globulin; GVHD: graft-versus-host disease; MMR: mismatched related donor; MRD: matched related donor; MMUD: mismatched unrelated donor; MUD: matched unrelated donor. Time to bone marrow engraftment: neutrophil engraftment.