Need for hemodialysis in patients undergoing hematopoietic stem cell transplantation: risk factors and survival in a retrospective cohort

Chapchap, Eduardo Cerello; Doher, Marisa Petrucelli; Kerbauy, Lucila Nassif; Belucci, Talita Rantin; Santos, Fabio Pires de Souza; Ribeiro, Andreza Alice Feitosa; Hamerschlak, Nelson

doi:10.1016/j.htct.2022.04.005

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Hematology, Transfusion and Cell Therapy

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Original article • Hematol., Transfus. Cell Ther. 45 (3) • Jul-Sep 2023 • https://doi.org/10.1016/j.htct.2022.04.005 copy

Need for hemodialysis in patients undergoing hematopoietic stem cell transplantation: risk factors and survival in a retrospective cohort

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) patients are exposed to acute and chronic nephrotoxic events (drugs, hypotension, infections, and microangiopathy). The need for hemodialysis (HD) may be associated with high mortality rates. However, the risk factors and clinical impact of HD are poorly understood.

Aim:

To analyze survival and risk factors associated with HD in allo-HSCT Patients and methods: single-center cohort study 185 (34 HD cases versus 151 controls) consecutive adult allo-HSCT patients from 2007-2019. We performed univariate statistical analysis, then logistic regression and competing risk regression were used to multivariate analysis. Survival was analyzed by Kaplan-Meier and Cox proportional-hazards models.

Results:

The one-year HD cumulative incidence was 17.6%. Univariate analysis revealed that HD was significantly associated with male gender, age (p 0.056), haploidentical donor, grade II-IV acute GVHD, polymyxin B, amikacin, cidofovir, microangiopathy, septic shock (norepinephrine use) and steroid exposure. The median days of glycopeptides exposure (teicoplanin/vancomycin) was 16 (HD) versus 10 (no HD) (p 0.088). In multivariate analysis, we found: norepinephrine (hazard ratio, HR:3.3; 95% confidence interval, 95%CI:1.2-8.9; p 0.024), cidofovir drug (HR:11.0; 95%CI:4.6 - 26.0; p < 0.001), haploidentical HSCT (HR:1.94; 95%CI:0.81-4.65; p 0.14) and Age (HR:1.01; 95%CI: 0.99-1.03; p 0.18). The HD group had higher mortality rate (HR:6.68; 95% CI: 4.1-10.9; p < 0.001).

Conclusion:

HD was associated with decreased survival in allo-HSCT. Carefully use of nephrotoxic drugs and improving immune reconstitution could reduce severe infections (shock) and patients requiring cidofovir, which taken together may result in lower rates of HD, therefore improving survival.

Keywords:
Allogeneic hematopoietic stem cell transplantation; Hemodialysis; Mortality; Risk factors; Stem cell transplantation

Clinical features	Hemodialysis group n (%) or median (range)	Hemodialysis-free group n (%) or median (range)	p-value
Mean age (range)	52.9 (23–76) (24–73)	48.1 (18–76) (22–74)	0.056#
Gender (male/female)	24/10 (70.6/29.4%)	79/72 (52.3/47.8%) (52.3/47.7%)	0.021
Diagnosis
AML/MDS	20 (62.5%)	79 (51.3%)
Myeloproliferative	2 (6.2%)	12 (7.8%)
ALL	6 (18.7%)	16 (10.4%)
Lymphoid and plasmocytic neoplasms	5 (15.6%)	33 (21.4%)
Bone marrow failure/hemoglobinopathies	0 (0%)	8 (5.2%) / 2 (1.3%)
Disease status
CR1 or CR2	15 (46.8%)	71 (53.9%)
CR3 or partial remission	2 (6.2%)	24 (18.1%)
Active disease	13 (40.6%)	37 (28.0%)	0.165
Conditioning
iv Bu/Flu ± ATG	16 (50%)	77 (50.3%)
Flu/Mel+TBI	7 (21.8%)	29 (18.9%)
Flu/Cy/TBI 200cGy¹⁴14 Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using non-myeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol blood and marrow transplant: j Am Society for Blood and Marrow Transplantation. 2008;14(6):641–50. https://doi.org/10.1016/j.bbmt.2008.03.005. https://doi.org/10.1016/j.bbmt.2008.03.0... or Flu/TBI	6 (18.7%)	21 (13.7%)
CYTBI 1200cGy	2 (6.2%)	9 (5.9%)
Other	3 (9.3%)	15 (9.8%)
GVHD prophylaxis
MTX + CNI	20 (60.6%)	111 (74.5%)
MMF + CNI + Cy post	13 (39.4%)	38 (25.5%)
Donor type
MRD	8 (23.5%)	59 (39.0%)
MUD/mismatch	9/3 (26.5%/8.8%)	48/6 (31.8%/4.0%)
Haploidentical	14 (41.2%)	38 (25.2%)	0.051
Bone marrow graft source	20 (62.5%)	79 (52.6%)
Peripheral blood graft source	12 (37.5%)	70 (45.7%)

Clinical outcome	Results	95% CI
Cumulative incidence of hemodialysis at 1 year	17.6%	13.1–28.0
Overall survival D+100	81.3%	75.1–86.3
Overall survival at 1-year	64.3%	58.0–71.2
Transplant-related mortality D+100	14.7%	7.0–26.5
Transplant-related mortality at 1 year	22.0%	12.0–36.1
Acute GVHD at 1 year	52.5%	–
Acute GVHD (II-IV) at 1 year	43.0%	–
Cumulative relapse incidence at 1 year	17.1%	11.4–34.5
Relapse related mortality at 1 year	14.6%	–

Risk factors	Dialysis n/total (%)	No dialysis n/total (%)	X2	p-value
Creatinine clearance (^a a Cockcroft-Gault equation ) pre-HSCT (Mean/95% CI)	130 (106–150)	123 (113–132)	–	0.276^# # Comparison using Student’s t-test.
Conditioning (myeloablative/RIC)	16/18 (47/53%)	72/79 (47.7/52.3%)	0.004	0.948
Mean age (95%CI)	52.9 (47.7–58.0) (47.7–58.0)	48.1 (45.6–50.7)(45.6–50.7)	–	0.056^# # Comparison using Student’s t-test.
Gender (male/female)	24/10 (70.6/29.4%)	79/72 (52.3/47.7%)	5.30	0.021
Haploidentical donor versus other	14/34 (41.2%)	38/151 (25.2%)	3.50	0.051
Septic shock (norepinephrine use)	26/31 (83.9%)	26/144 (18.0%)	28.41	< 0.001
Cidofovir	20/31 (64.5%)	5/145 (3.4%)	78.15^* * P-values calculated by the Fisher’s exact test and association factor calculated by the Chi-squared test with Yates correction. # Comparison using Student’s t-test.	< 0.001^* * P-values calculated by the Fisher’s exact test and association factor calculated by the Chi-squared test with Yates correction. # Comparison using Student’s t-test.
Polymyxin B	8/30 (26.7%)	9/144 (6.25%)	11.74	0.003^* * P-values calculated by the Fisher’s exact test and association factor calculated by the Chi-squared test with Yates correction. # Comparison using Student’s t-test.
Amikacin	9/29 (31.0%)	17/144 (11.8%)	6.99	0.019^* * P-values calculated by the Fisher’s exact test and association factor calculated by the Chi-squared test with Yates correction. # Comparison using Student’s t-test.
Thrombotic microangiopathy (TAM)	13/31 (41.9%)	7/66 (0.6%)	12.65	0.001
Glycopeptide (teicoplanin/vancomycin)	13/30 (43.3%)	92/140 (65.7%)	5.24^* * P-values calculated by the Fisher’s exact test and association factor calculated by the Chi-squared test with Yates correction. # Comparison using Student’s t-test.	0.037
Duration of glycopeptide (days)(median and nge)	16 (1–55)	10 (1–59)	–	0.088
CNI duration (time in days post-HSCT) (median and range)	137 (14–597)	519 (74 – 1,364)	–	< 0.001
Time to neutrophil engraftment (days) (median d range)	17 (11–30)	15 (10–22)	–	0.007
Amphotericin B	8/31 (25.8%)	49/143 (34.3%)	0.83	0.406
Steroid exposure (^b b prednisone ≥ 20 mg/day or equivalent longer than 14 days. )	26/30 (86.6%)	86/146 (59%)	3.75	0.039
Acute GVHD (II–IV)	20/34 (58.8%)	55/151 (36.4%)	5.78	0.020
Active disease vs. other disease status pre-HSCT	13/32 (40.6%)	37/132 (28.0%)	1.93	0.165
Allo-HSCT period (2007–2014 us. 2015–2019)	24/10 (20.7%/14.5%)	92/59 (79.3%/85.5%)	1.10	0.293

Risk factors	HR	95%CI	p-value
Septic shock (norepinephrine use)	3.30	1.20–8.90	0.024
Cidofovir	11.0	4.60–26.01	< 0.001
Haploidentical transplant	1.94	0.81–4.65	0.140
Age	1.01	0.99–1.03	0.180

Case	Sepsis + VAD	Drug	Drug class	TAM	Viral infection	SOS	Dialysis indication
1	++	+	Teicoplanin				Lab clearance
2		++	Cidofovir	+	+		Lab clearance + anuria
3	++	+	Contrast			+	Lab clearance
4	+	+	Amikacin			+++	Volume overload
5		++	Cidofovir	++	+		Lab clearance
6	++	++	≥ 3 drugs				Lab clearance
7	++	+	Polymyxin B				Lab clearance
8	++	++	Teicoplanin/foscarnet/polyb				Volume overload + anuria
9	++	++	Polymyxin B/cidofovir	+			Unknown
10	+++	+	Polymyxin B				Unknown
11	+++	+	Polymyxin B				Lab clearance
12	++	+	Cidofovir	+	+		Lab clearance
13	+++	+	Polymyxin B				Lab clearance
14	+++	+	Amikacin				Unknown
15	+++	+	Amikacin				Lab clearance + anuria
16	+	++	Teicoplanin/cidofovir	+	+		Unknown
17	+++		Amphotericin b				Lab clearance + anuria
18	+	+	Vancomycin				Lab clearance
19		++	CNI/teicoplanin	+	+	+	Unknown
20	++		No		+		Unknown
21	++	+	Cidofovir		+		Lab clearance
22			No			+++	Volume overload
23^* * Case #23 needed dialysis in two moments, the first was considered for the analysis.		+	Foscarnet/vancomycin			+++	Volume overload
23^* * Case #23 needed dialysis in two moments, the first was considered for the analysis.		++	Foscarnet/teicoplanin	++			Volume overload
24	+++	+	≥ 3 drugs				Lab clearance
25		+++	Cidofovir/amphotericin B		+		Lab clearance
26	+++	+	Amikacin/furosemide				Lab clearance + anuria
27		+	Teicoplanin	+++			Volume overload + uremia
28			No	+++			Volume overload
29	+++	+	Amikacin/amphotericin B				Lab clearance
30	++	+	CNI	+			Lab clearance + electrolytic disturbance
31	+	+	CNI	++			Uremia
32	+++	+	Teicoplanin				Lab clearance + anuria
33	+	++	Cidofovir		+	+	Lab clearance + anuria
34	M	M	M	M	M	M	M

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] *Corresponding author at: Dayan-Daycoval Family Hematology and Oncology Center, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/520, São Paulo, SP, CEP 05256-900 Brazil. E-mail address: eduardo.cerello@einstein.br (E.C. Chapchap).