Health Related Quality of Life in stem cell transplantation: Clinical and psychometric validation of the questionnaire module, High Dose Chemotherapy (HDC-19)

Figures & data

Figure 1.  Attrition of patients from approach to one year follow-up.

Table I.  Clinical and demographic data at inclusion (n = 202).

	N (%)
Sex
Male	121 (60%)
Female	81 (40%)
Age Mean (SD)	51.5 (11.2)
Median(min-max)	54 (19–70)
Employment
Employed	42 (21%)
Retired	24 (12%)
On sick-list	49 (24%)
Student	2 (1%)
Unknown	85 (42%)
Marital status
Married	146 (72%)
Single	35 (17%)
Unknown	21 (10%)
Diagnosis^1
Lymphoma	66 (32%)
Multiple myeloma	58 (28%)
AL	31 (15%)
CL	14 (7%)
Solid tumors	14 (7%)
Other	19 (9%)
Transplantation
Autologous	145 (72%)
Allogeneic	57 (28%)
Clinical status^2
CR I–II	67 (33%)
PR I–III	91 (48%)
CP	9 (5%)
Not available	35 (14%)
Conditioning^3
Melphalan	62 (31%)
BEAM	62 (31%)
Cy/TBI	16 (8%)
Flu/Bu	16 (8%)
Cy/Bu	14 (7%)
Other	23 (11%)

¹AL = Acute Leukaemia; CL = Chronic Leukemia; Other = Amyloidos (8 patients), Myelodysplastic Syndrome (5 patients), Mb Waldenström (1 patient), Myelofibrosis (3 patients), Aplastic Anaemia (1 patient), SLE (1 patient).

²CR = Complete Remission; PR = Partial Remission; CP = Chronic Phase.

³BEAM = BCNU, Etoposid, ARA-C and Melphalan; Cy/TBI= Cyclophosphamide/Total Body Radiation; Flu/Bu = Fludarabin/Busulphan; Cy/Bu = Cyclophosphamide/Busulphan.

Table II.  Item convergent validity, Cronbach's alpha and item/scale discriminatory validity of the four potential multi-item scales in HDC19.

	Health worries 3 items	Sexual functioning 2 items	Joint and muscle pain 2 items	Skin irritations 2 items
Time 1 inclusion (n = 171)
Mean(Range) convergent validity^a	.73 (.64–.82)	.76 (.76–.76)	.42 (.42–.42)	.46 (.46–.46)
Cronbach's alpha	.86	.86	.59	.62
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/50/50	0/0/0/100
Time 2 baseline (n = 149)
Mean(Range) convergent validity^a	.76 (.67–.84)	.78 (.78–.78)	.51 (.51–.51)	.49 (.49–.49)
Cronbach's alpha	.87	.88	.67	.65
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/13/87	0/0/0/100
Time 3 1 month after tx (n = 158)
Mean(Range) convergent validity^a	.75 (.63–.84)	.73 (.73–.73)	.46 (.46–.46)	.36 (.36–.36)
Cronbach's alpha	.87	.83	.63	.49
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/0/100	0/37/37/25
Time 4 3 monts after tx (n = 149)
Mean(Range) convergent validity^a	.75 (.68–.83)	.76 (.76–.76)	.56 (.56–.56)	.38 (.38–.38)
Cronbach's alpha	.87	.91	.72	.55
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/0/100	0/0/37/63
Time 5 6 months after tx (n = 139)
Mean(Range) convergent validity^a	.78 (.72–.82)	.71 (.71–.71)	.63 (.63–.63)	.48 (.48–.48)
Cronbach's alpha	.89	.83	.77	.65
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/0/100	0/0/0/100
Time 6 12 months after tx (n = 132)
Mean(Range) convergent validity^a	.81 (.72–.86)	.77 (.77–.77)	.55 (.55–.55)	.53 (.53–.53)
Cronbach's alpha	.90	.87	.71	.69
Percent success rate discrimin. validity^b	0/0/0/100	0/0/0/100	0/0/0/63	0/0/25/75

^aCorrelations between items and hypothesized scale corrected for overlap.

^bPercent correlations that are ‘significantly lower/lower/higher/significantly higher’ with hypothesized scale compared to other scales.

Table III.  Means (SD) of the HDC19.

	No. of items	Inclusion	Baseline	1 month after tx	3 months after tx	6 months after tx	12 months after tx
Functioning scales^a
Sexual functioning	2	23.5 (23.9)	24.8 (24.5)	14.4 (20.2)	24.3 (22.2)	27.3 (23.6)	30.5 (26.1)
Sexual enjoyment	1	62.4 (26.0)	64.9 (25.0)	53.7 (26.7)	56.1 (23.2)	64.4 (25.7)	61.3 (24.8)
Future health perspect.	3	64.3 (27.6)	66.2 (26.9)	65.3 (27.2)	68.3 (26.4)	69.4 (26.1)	66.1 (27.7)
Someone to talk to	1	57.4 (33.4)	58.8 (32.3)	52.3 (35.0)	52.2 (36.2)	54.6 (33.9)	52.9 (36.1)
Symptom scales^b
Joint and muscle pain	2	24.4 (23.6)	21.8 (23.1)	23.5 (21.5)	32.5 (25.3)	26.9 (25.5)	28.6 (23.7)
Skin irritations	2	17.4 (18.7)	16.3 (17.7)	24.5 (21.7)	19.5 (20.2)	20.0 (21.4)	20.0 (22.2)
Felt cold more easily	1	24.9 (27.2)	21.1 (25.2)	44.1 (28.8)	30.1 (29.3)	20.2 (26.4)	19.8 (23.4)
Been dizzy	1	13.7 (8.24)	10.7 (18.4)	20.7 (25.1)	12.3 (18.7)	11.0 (18.4)	11.8 (19.2)
Increased mucous prod.	1	8.2 (17.9)	5.9 (14.6)	18.5 (30.3)	10.2 (18.8)	5.3 (15.6)	8.5 (20.6)
Soreness in the mouth	1	2.4 (10.6)	1.6 (8.32)	8.7 (20.5)	3.3 (12.5)	5.5 (15.7)	5.1 (15.0)
Dry mouth	1	16.9 (25.9)	14.1 (22.6)	33.1 (32.0)	29.2 (32.1)	24.6 (30.9)	20.0 (26.0)
Change of taste	1	19.3 (27.6)	15.8 (25.7)	51.6 (32.5)	21.6 (28.1)	14.6 (26.9)	10.6 (22.4)
Worries about sterility	1	7.1 (21.2)	8.7 (23.5)	7.5 (21.3)	6.3 (18.4)	.1 (21.6)	6.6 (21.3)
Potency problems	1	37.2 (36.2)	33.3 (35.5)	48.9 (37.5)	36.1 (38.1)	35.9 (33.0)	36.4 (38.1)

^aScores range from 0 to 100, with higher scores representing higher level of functioning.

^bScores range from 0 to 100, with higher scores representing higher levels of symptoms.

Table IV.  Percent at floor and ceiling of the HDC-19.

	Inclusion		Baseline		1 month after tx		3 months after tx		6 months after tx		12 months after tx
	% floor	% ceil.	% floor	% ceil.	% floor	% ceil.	% floor	% ceil.	% floor	% ceil.	% floor	% ceil.
Functioning scales^a
Sexual functioning	37	1	37	1	56	1	35	0	32	0	27	3
Sexual enjoyment^b	1	23	2	24	5	15	3	11	1	25	0	21
Future health perspect.	6	14	7	15	5	17	5	20	6	18	5	22
Someone to talk to	14	26	13	27	19	23	21	25	16	24	19	27
Symptom scales^c
Joint and muscle pain	33	1	37	1	31	1	20	2	30	2	24	1
Skin irritations	40	0	42	0	26	2	36	1	36	1	39	0
Felt cold more easily	45	4	49	4	15	11	39	5	55	3	52	1
Been dizzy	68	1	68	1	52	2	67	0	70	1	70	0
Increased mucous prod.	80	1	80	1	68	6	75	0	88	0	83	1
Soreness in the mouth	94	0	96	0	81	2	92	1	87	1	88	1
Dry mouth	63	3	65	3	37	9	44	9	51	8	54	4
Change of taste	60	5	61	5	16	19	55	4	72	5	78	1
Worries about sterility	88	3	85	3	87	3	87	2	88	4	89	3
Potency problems	39	14	40	15	26	24	43	18	32	13	45	17

^aHigher scores represent higher level of functioning.

^bNote that respondents were requested to answer this question only if they were sexually active.

^cHigher scores represent higher levels of symptoms.

Table V.  Test-retest agreement between the assessments at inclusion and baseline. Intraclass correlations (ICC) and limits of agreement (M_d±1.96×SD_d).

	ICC	Limits of agreement
Functioning scales
Sexual functioning	0.99	0.11±4.6
Sexual enjoyment	0.98	0.54±8.3
Future health perspective	0.99	−0.15±5.0
Someone to talk to	0.98	0.22±9.3
Symptom scales
Joint and muscle pain	0.96	0.00±10.5
Skin irritations	0.96	0.64±9.0
Felt cold more easily	0.98	0.43±7.4
Been dizzy	0.96	−0.21±9.1
Increased mucous production	0.98	−0.21±5.3
Soreness in the mouth	1.00	0.00±0.0
Dry mouth	0.97	0.22±9.1
Change of taste	0.99	−0.21±5.2
Worries about sterility	0.97	−0.68±9.3
Potency problems	0.99	−0.39±7.2

Table VI.  Known-groups comparisons. Patients with myeloma (n = 47) versus lymphoma (n = 47); Patients with complete remission (CR) (n = 61) versus partial remission (PR) (n = 44); Patients with related donor (RD) (n = 20) versus unrelated donor (URD) (n = 26). Mean values (SD) and p-values from independent t-tests one month after transplantation are presented.

	Myeloma – Lymphoma	p	CR – PR	p	RD – URD	p
Functioning scales
Sexual functioning	17.7 (23.9)–13.1 (17.0)	0.28	11.9 (18.4)–19.5 (20.0)	0.05	20.9 (26.9)–9.6 (16.4)	0.09
Sexual enjoyment	51.3 (25.9)–48.5 (22.9)	0.78	57.1 (30.5)–48.9 (21.3)	0.40	61.9 (35.6)–50.0 (43.0)	0.63
Future health perspective	56.2 (29.7)–68.3 (26.2)	0.04	66.8 (23.2)–70.2 (26.1)	0.49	67.2 (28.7)–72.2 (20.7)	0.49
Someone to talk to	55.8 (39.2)–39.4 (28.1)	0.03	57.6 (32.7)–40.0 (34.8)	0.01	57.9 (34.9)–64.1 (32.6)	0.54
Symptom scales
Joint and muscle pain	27.6 (21.9)–19.4 (19.9)	0.05	23.7 (23.5)–20.1 (18.5)	0.39	20.9 (20.9)–26.3 (23.7)	0.42
Skin irritations	24.8 (26.4)–20.4 (18.1)	0.34	25.4 (19.2)–22.3 (21.2)	0.44	26.7 (23.2)–25.6 (17.2)	0.86
Felt cold more easily	38.8 (29.1)–44.2 (28.3)	0.35	49.2 (25.5)–36.4 (26.7)	0.01	53.3 (27.4)–46.2 (29.9)	0.41
Been dizzy	14.9 (22.6)–23.1 (25.6)	0.10	23.5 (27.4)–21.2 (23.9)	0.65	20.0 (27.4)–24.6 (29.2)	0.61
Increased mucous production	23.8 (31.9)–23.1 (33.5)	0.92	19.1 (31.9)–18.2 (27.3)	0.87	20.0 (34.9)–7.7 (19.6)	0.14
Soreness in the mouth	12.2 (24.2)–6.8 (15.2)	0.19	9.2 (22.9)–7.6 (20.2)	0.62	10.0 (26.7)–7.7 (21.7)	0.75
Dry mouth	36.1 (31.8)–38.9 (31.7)	0.66	37.2 (33.9)–24.0 (27.5)	0.04	30.0 (35.7)–20.5 (28.4)	0.32
Change of taste	57.1 (33.3)–51.0 (34.1)	0.37	54.6 (32.8)–46.9 (28.1)	0.21	48.3 (29.6)–44.9 (32.6)	0.71
Worries about sterility	2.8 (9.40)–8.5 (22.5)	0.11	5.7 (16.7)–9.8 (23.4)	0.30	8.7 (26.9)–14.7 (30.6)	0.51
Potency problems	60.5 (37.0)–54.8 (35.0)	0.55	45.6 (35.5)–54.8 (34.2)	0.32	33.3 (30.9)–40.0 (44.0)	0.71

Table VII.  Mean (SD) changes from baseline, p-values and Standardised Response Means (SRM).

	Baseline – 1 month			Baseline – 3 months			Baseline – 6 months			Baseline – 12 months
	Mean (SD) change from baseline	p-value	SRM^c	Mean (SD) change from baseline	p-value	SRM^c	Mean (SD) change from baseline	p-value	SRM^c	Mean (SD) change from baseline	p-value	SRM^c
Functioning scales^a
Sexual functioning	−8.6 (23.9)	0.00	0.38	−0.1 (21.6)	0.31	0.09	+3.9 (24.3)	0.07	0.16	+6.5 (26.3)	0.01	0.25
Sexual enjoyment	−13.8 (30.2)	0.02	0.48	−4.2 (24.4)	0.16	0.21	+3.8 (21.8)	0.26	0.18	+0.0 (25.0)	0.99	0.00
Future health perspec.	+0.8 (21.7)	0.96	0.00	+4.4 (28.5)	0.11	0.15	+5.3 (22.3)	0.01	0.24	+3.1 (22.7)	0.13	0.14
Someone to talk to	−4.8 (29.6)	0.18	0.13	−6.2 (28.5)	0.04	0.20	−4.4 (30.7)	0.12	0.14	−6.5 (25.4)	0.07	0.18
Symptom scales^b
Joint and muscle pain	+0.2 (21.1)	0.63	0.04	+9.6 (23.9)	0.00	0.45	+5.3 (28.2)	0.03	0.19	+6.5 (25.4)	0.01	0.26
Skin irritations	+8.1 (23.3)	0.00	0.36	+3.7 (21.8)	0.03	0.20	+4.0 (24.1)	0.06	0.17	+4.1 (26.0)	0.08	0.16
Felt cold more easily	+20.5 (32.4)	0.00	0.74	+5.1 (29.6)	0.01	0.24	−2.0 (30.5)	0.45	0.06	−2.9 (27.8)	0.24	0.11
Been dizzy	+.6.2 (29.5)	0.00	0.31	+2.1 (22.8)	0.42	0.07	−2.8 (23.3)	0.17	0.12	−1.9 (26.4)	0.43	0.07
Increased mucous prod.	+10.0 (30.2)	0.00	0.39	+2.2 (22.8)	0.02	0.21	−3.03 (18.2)	0.06	0.17	−0.0 (23.1)	0.99	0.00
Soreness in the mouth	+7.3 (21.6)	0.00	0.32	+0.7 (12.3)	0.37	0.08	+4.5 (15.8)	0.00	0.29	+2.6 (15.5)	0.06	0.17
Dry mouth	+17.5 (32.7)	0.00	0.60	+11.8 (20.3)	0.00	0.46	+9.1 (30.6)	0.00	0.30	+4.5 (31.7)	0.11	0.14
Change of taste	+31.9 (36.9)	0.00	0.94	+1.7 (30.3)	0.22	0.11	−3.8 (34.9)	0.21	0.11	−7.4 (32.9)	0.01	0.23
Worries about sterility	−1.5 (15.6)	0.36	0.08	−2.3 (17.1)	0.17	0.13	−1.4 (16.2)	0.36	0.08	−1.72 (18.6)	0.32	0.09
Potency problems	+10.7 (35.7)	0.01	0.34	+4.4 (35.2)	0.72	0.05	1.9 (32.3)	0.06	0.06	−1.5 (41.2)	0.77	0.04

^aHigher scores indicate better functioning.

^bHigher scores indicate more symptoms.

^cThe thresholds suggested by Cohen (1988) are; small (0.2–0.5), moderate (0.5–0.8) and large (above 0.8).