Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study

Figures & data

Table 1 Patients’ Baseline Demographic and Clinical Characters

Baseline Characters	n=101
Age (year) median (min, max)	46 (14, 83)
Sex
Male n (%)	49 (48.5)
Female n (%)	52 (51.5)
Hemoglobin (g/L) mean (SD)	61.88 (28.13)
Reticulocyte (10^12/L) mean (SD)	6.13 (10.01)
White cell count (10^9/L) mean (SD)	3.08 (1.03)
Neutrophil count (10^9/L) mean (SD)	1.32 (0.80)
Platelet (10^9/L) mean (SD)	38.26 (62.50)
SGPT (U/L) mean (SD)	26.88 (24.48)
Scr (μmol/L) mean (SD)	98.56 (58.66)
SF (μg/L) mean (SD)	1761.23 (1937.18)
CD4+/CD8+ ratio mean (SD)	0.94 (0.54)
Glu (mmol/L) mean (SD)	6.51 (3.97)
Notable PNH clone n (%)	7 (6.9)
RBC transfusion dependent n (%)	50 (49.5)
Platelet transfusion dependent n (%)	26 (25.7)
Chromosome abnormalities
+8 n (%)	5 (5.0)
-Y n (%)	3 (3.0)
20q- n (%)	2 (2.0)
Monosomy 7 n (%)	1 (1.0)

Abbreviations: SD, standard deviation; SGPT, serum glutamate pyruvate transaminase; Scr, serum creatinine; SF, serum ferritin; PNH, paroxysmal nocturnal hemoglobinuria.

Table 2 Patients’ Response in Different Groups

		Number	CR (N/%)	P* value	PR (N/%)	P^& value	ORR (N/%)	P^# value
Gender	Male	49	2(4.1)	0.09338	12(24.5)	0.3625	14(28.6)	0.0442
	Female	52	8(15.4)		17(32.7)		25(48.1)
Age (range)years	≤50	58	6(10.3)	1	23(39.7)	0.0033	29(50.0)	0.004
	>50	43	4(9.3)		6(14.0)		10(23.3)
CsA	Refractory/relapsed	81	7 (8.6)	0.4103	22(27.2)	0.4877	29(35.8)	0.2429
	Intolerant	20	3 (15.0)		7(35.0)		10 (50.0)
FK concentration	<4.0ng/mL	44	2(4.5)	0.0977	8(18.2)	0.0126	10(22.7)	0.0005
	4.0~12ng/mL	50	8(13.6)		21(35.6)		29(49.2)

Notes: *P value indicate the comparison of CR among different groups, ^&P value indicate the comparison of PR among different groups, #P value indicate the comparison of ORR among different groups.

Abbreviations: CR, complete response; PR partial response; ORR, overall response rate; FK, tacrolimus.

Table 3 Multivariate Analysis for the Factors Associated with ORR

	Coefficient	Standard Error	OR	Lower Bound 95% CI	Upper Bound 95% CI	P value
Male(ref=Female)	−0.7727	0.5187	0.462	0.167	1.276	0.1363
Age (year)	−0.0660	0.0191	0.936	0.902	0.972	0.0005
FK (4~12 ng/mL)	1.9729	0.5636	7.192	2.383	21.706	0.0005
refractory/relapse (ref=intolerant)	−1.7391	0.7090	0.176	0.044	0.705	0.0142

Abbreviations: ORR, overall response rate; OR, odds ratio; CI, confidence interval; ref, reference; FK, tacrolimus.

Figure 1 Regulatory T cells in peripheral blood before and after FK. (A) Total events of 50,000 were gated based on FSC and SSC characteristics, and dot plots for T_reg cells were gated on CD4+ cells. T_reg cells were defined as CD4+CD25+foxP₃+ co-expression and expressed as a percentage of the total CD4+ T population. (B) The expression of T_reg cells from 31 patients who achieved at least PR was tested before and 6 months after FK treatment. Eight age- and sex-matched normal volunteers were used as controls. Levels of T_reg cells pre-FK were much lower compared to healthy controls, but increased significantly after FK treatment. FSC, forward-scatter characteristics; SSC, side-scatter characteristics; T_reg cells, T regular cells; FK, tacrolimus; PR, partial response.