Hyperbaric oxygen therapy improves the efficacy of conventional supportive treatment for late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Figures & data

Table 1. General clinical data of HC patients.

Case	Sex	Age (years)	Diagnosis	Clinical status	Transplantation mode	Conditioning regimen	GvHD prophylaxis	GvHD (type)	GvHD (grade)
1	F	37	ALL	CR	MUD-HSCT	Etoposide, BuCy, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous, gastrointestinal	I
2	M	19	ALL	CR	Haplo-HSCT	Etoposide, BuCy, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous, gastrointestinal	IV
3	F	21	AML	CR	Haplo-HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous, gastrointestinal	II
4	M	48	ALL	CR	Haplo-HSCT	TBI, Cy, Ara-C, FLU	ATG, short-course MTX, CsA, MMF	None	0
5	M	42	NHL	CR	MSD-HSCT	BuCy, attenuated-dose Ara-C, Semustine, ATG, FLU	ATG, short-course MTX, CsA	Cutaneous, gastrointestinal	II
6	F	25	ALL	CR	Haplo-HSCT	Decitabine, BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Gastrointestinal	II
7	M	30	T-LBL	CR	Haplo-HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous, gastrointestinal	II
8	M	51	AML	CR	Haplo-HSCT	Decitabine, BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Gastrointestinal	II
9	M	53	AML	CR	MSD-HSCT	Decitabine, BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous	I
10	F	49	AML	CR	Haplo-HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	None	0
11	F	24	AML	CR	Haplo-HSCT	Etoposide, BuCy, ATG, FLU	ATG, short-course MTX, CsA, MMF	Gastrointestinal, liver	III
12	M	43	MDS	CR	Haplo-HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	None	0
13	M	59	AML	CR	Haplo-HSCT	Decitabine, BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Gastrointestinal	II
14	M	62	MDS	CR	MUD-HSCT	Decitabine, BuCy, Ara-C, FLU, ATG	ATG, short-course MTX, CsA, MMF	Cutaneous, gastrointestinal	III
15	F	48	ALL	CR	MSD -HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Gastrointestinal	II
16	F	30	ALL	CR	MSD -HSCT	BuCy, Ara-C, Semustine, ATG	ATG, short-course MTX, CsA, MMF	Gastrointestinal	II

Case	HBOT	Onset days after transplantation	Hematuria (grade)*	Clinical symptoms of HC	Time of conventional treatment (days)	Ultrasound	Anti-viral treatment before HBOT	Outcomes after HC treatment.	Time of HBOT (days)
1	+	31	III	Frequent urination, pain, gross hematuria	24	Normal	Ganciclovir	CR	10
2	+	32	III	Frequent urination, terminal pain, gross hematuria, blood clots	29	Bladder wall thickening and roughing	Foscarnet Sodium, Aciclovir	PR	25
3	+	24	I	Lack of urination, pain, and gross hematuria after urination	22	Normal	Ganciclovir	CR	12
4	+	52	III	Frequent urination, terminal urination pain, flesh-water urine, small blood clots	12	Not performed	Ganciclovir	CR	5
5	+	34	II	Pain, and discomfort of the urethra, gross hematuria, and small blood clots.	14	Bladder wall thickening and roughing	Ganciclovir, entecavir	CR	11
6	+	21	I	Persistent pain in urine	17	Normal	Ganciclovir	CR	5
7	+	40	II	Pain after urination, morning onset, gross hematuria, blood clots	12	Bladder wall thickening and roughing	Ganciclovir, Foscarnet sodium	PR	9
8	+	36	III	Dysuria, gross hematuria, blood clots	10	Bladder wall roughing	Ganciclovir	CR	6
9	−	31	II	Pain, and discomfort of the urethra, gross hematuria, and small blood clots.	22	Bladder wall thickening and roughing	Foscarnet sodium	CR	0
10	−	21	I	Persistent pain in urine	24	Bladder wall thickening and roughing	Ganciclovir	CR	0
11	−	14	III	Frequent urination, terminal urination pain, flesh-water urine, small blood clots	84	Bladder wall thickening and roughing	Ganciclovir, foscarnet sodium	Death	0
12	−	61	III	Frequent urination, terminal urination pain, flesh-water urine, small blood clots	16	Bladder wall thickening and roughing	Ganciclovir, foscarnet sodium	CR	0
13	−	38	II	Pain, and discomfort of the urethra, gross hematuria, and small blood clots.	26	Bladder wall thickening and roughing	Ganciclovir, foscarnet sodium	CR	0
14	−	58	III	Frequent urination, terminal urination pain, flesh-water urine, small blood clots	114	Bladder wall thickening and roughing	Foscarnet sodium	Death	0
15	−	20	II	Pain, and discomfort of the urethra, gross hematuria, and small blood clots.	46	Bladder wall thickening and roughing	Ganciclovir, foscarnet sodium	PR	0
16	−	33	III	Frequent urination, terminal urination pain, flesh-water urine, small blood clots	31	Bladder wall thickening and roughing	Foscarnet Sodium, Aciclovir, Ganciclovir	PR	0

ALL acute lymphoblastic leukemia, AML acute myeloid leukemia, NHL Non-Hodgkin lymphoma, T-LBL T-cell lymphoblastic lymphoma, TBI total body irradiation, CR completely response, Bu busulfan, Cy cyclophosphamide, ATG anti-thymocyte globulin, Ara-C cytarabine, FLU fludarabine, MTX methotrexate, CsA cyclosporine, MMF mycophenolate, Haplo-HSCT haploidentical hematopoietic stem cell transplantation, MUD matched unrelated donor, MSD matched sibling donor, HLA human leukocyte antigen.

* Diagnosis of HC [6]: The diagnostic criteria of HC refer to the literature. The World Health Organization (WHO) classifies the clinical classification of HC according to the degree of hematuria: I: microscopic hematuria; II: carnal hematuria; III: carnal hematuria with clots; IV: clots obstructing the urethra, requiring measures to remove the clots or requiring surgical intervention. The patient’s HC grade is based on the highest grade that occurs in the course of the disease.

Figure 1. Treatment of HC.

Table 2. Comparison of Patient characteristic data before HBOT in two groups.

	Sex	Age	GVHD grading	HC grade	NRS	NRS after treatment	HC grading after treatment	Time to onset of HC (days after transplantation)
Z	0.488	1.788	0.465	0.229	1.473	0.812	1.243	0.316
P	0.626*	0.074*	0.642*	0.819*	0.141*	0.417*	0.214*	0.752*

*P > 0.05, there was no statistical significance.

Figure 2. Time after occurrence of HC (day) P = 0.0175 < 0.05.

Table 3. The treatment time of the two groups.

Group	M (P25, P75)	Median difference (95% CI)	Wilcoxon Mann-Whitney
			Z	P
HBOT(+) (n = 8)	15.5 (12.0, 23.5)	14.0 (2.0–62.0)	2.421	0.015*
HBOT(−) (n = 8)	28.5 (22.5, 74.5)

* P < 0.05, the difference was statistically significant.

Figure 3. There was no statistically significant difference in the analysis of the 2-year survival rates between the two transplantation groups. P = 0.0851 > 0.05.

Table 4. Type of viruses.

Case	HBOT	Serum CMV-DNA (copies/ml)*		Urine CMV-DNA (copies/ml)*		Urine BKV-DNA
		Before the treatment	After the treatment	Before the treatment	After the treatment
1	+	5.67E+02	<1.00E+03	1.50E+02	<1.00E+03	+
2	+	5.81E+02	<1.00E+03	9.9E+03↑	<1.00E+03	+
3	+	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
4	+	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
5	+	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
6	+	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
7	+	5.46E+03↑	1.95E+02	<1.00E+03	<1.00E+03	+
8	+	1.15E+03↑	<1.00E+03	6.10E+02	<1.00E+03	+
9	−	2.418E+03↑	2.220E+03↑	2.418E+03↑	<1.00E+03	+
10	−	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
11	−	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
12	−	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
13	−	<1.00E+03	<1.00E+03	<1.00E+03	<1.00E+03	+
14	−	<1.00E+03	<1.00E+03	<1.00E+03	1.52E+05↑	+
15	−	2.71E+04↑	<1.00E+03	<1.00E＋03	<1.00E+03	+
16	−	3.01E+04↑	<1.00E+03	<1.00E+03	<1.00E+03	+

* The normal value of serum CMV-DNA is <1.00E + 03 copies/ml; the normal value of urine CMV-DNA is <1.00E + 03 copies/ml.

Savva-Bordalo J, Pinho Vaz C, Sousa M, et al. Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2012;47(8):1095–1098. doi:10.1038/bmt.2011.228

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