Humoral immune response of childhood acute lymphoblastic leukemia survivors against the measles, mumps, and rubella vaccination

Figures & data

Table 1. Differing ALL children characteristics.

Variable	Number of patients (%)
Sex	28(49.1) 29(50.9)
Male Female
Age at ALL diagnosis
Mean ± SD Median (IQR) [Minimum–Maximum]	5.33 ± 3.24 year 4.0 (3.20–7.10) year [2.4–14.0] year
Age at antibodies testing (sampling)
Mean ± SD Median (IQR) [Minimum–Maximum]	12.31 ± 3.28 year 11.50 (10.0–15.0) year [6.10–18.0] years
Duration from end of treatment to testing
Mean ± SD Median (IQR) [Minimum–Maximum]	5.50 ± 2.34 year 4.90 (3.9–7.25) year [1.50–11.7] year
Risk classification and treatment received	34(59.6) 23(40.4)
Standard/intermediate risk High risk
General immunization status	35(61.4) 22(38.6) 14(24.6) 8(14.0)
Seropositive for 3 viruses (protected)
Seronegative (unprotected)
Seronegative to at least 1 virus Seronegative to all 3 viruses
Seronegative patients for each virus(unprotected)
Measles Mumps Rubella	14(24.6) 16(28.1) 14(24.6)

Note: IQR: inter quartile range (25th–75th percentile); SD: standard deviation.

Table 2. Comparative differentiation criteria with respect to patients MMR response.

	Measles			Mumps			Rubella
	Seropositive 43 patients (75.4%)	Seronegative 14 patients (24.6%)	p	Seropositive 41 patients (71.9%)	Seronegative 16 patients (28.1%)	p	Seropositive 43 patients (75.4%)	Seronegative 14 patients (24.6%)	p
Sex
Male (28 patients)	21(36.8)	7(12.3)	0.93	21(36.8)	7(12.3)	0.61	22(38.6)	6(10.5)	0.58
Female (29 patients)	22(38.6)	7(12.3)		20(35.1)	9(15.8)		21(36.8)	8(14.0)
Age on diagnosis
<5years (31 patients)	20(35.1)	11(19.3)	0.03*	17(29.8)	14(24.6)	0.001*	19(33.3)	12(21.1)	0.006*
>5 years(26 patients)	23(40.4)	3(5.7)		24(42.1)	2(3.5)		24(42.1)	2(3.5)
Age on testing
<10 years (22patients)	16(28.1)	6(10.5)	0.70	17(29.8)	5(8.8)	0.47	17(29.8)	5(8.8)	0.79
>10 years (35 patient)	27(47.4)	8(14.0)		24(42.1)	11(19.3)		26(45.6)	9(15.8)
Risk and treatment received
Standard/intermediate risk (34 patients)	24(42.1)	10(17.5)	0.30	26(45.6)	8(14.0)	0.43	26(45.6)	8(14.0)	0.82
High risk (23 patients)	19(33.3)	4(7.0)		15(26.3)	8(14.0)		17(29.8)	6(10.5)
Time of sample collection from end of treatment
<3 years (24 patients)	20(35.1)	4(7.0)	0.49	19(33.3)	5(8.8)	0.34	20(35.1)	4(7.0)	0.16
3–5 years (16 patients)	11(19.3)	5(8.8)		12(21.1)	4(7.0)		13(22.8)	3(5.7)
>5 years (17patients)	12(21.1)	5(8.8)		10(17.5)	7(12.3)		10(17.5)	7(12.3)

*p of significance if <0.05.

Figure 1. Flow chart of the research study.

Table 3. Comparative differentiation criteria with respect to patients’ response after a booster MMR vaccine administration.

	Measles 14 patients (100%)			Mumps 16 patients (100%)			Rubella 14 patients (100%)
	Seropositive 8 patients (57.1%)	Seronegative 6 patients (42.9%)	p	Seropositive 14 patients (87.5%)	Seronegative 2 patients (12.5%)	p	Seropositive 11 patients (78.6%)	Seronegative 3 patients (21.4)	p
Sex
Male	4(28.6)	3(21.4)	1.0	7(43.75)	1(6.25)	1.0	5(35.7)	1(7.1)	0.7
Female	4(28.6)	3(21.4)		7(43.75)	1(6.25)		6(42.9)	2(14.3)
Age on diagnosis
<5 years	3(21.4)	4(28.6)	0.28	4(25.0)	2(12.5)	0.05	4(28.6)	2(14.3)	0.34
>5 years	5(35.7)	2(14.3)		10(62.5)	0		7(50.0)	1(7.1)
Age on testing
<10 years	4(28.6)	2(14.3)	0.53	6(37.5)	1(6.25)	0.84	3(21.4)	2(14.3)	0.20
>10 years	4(28.6)	4(28.6)		8(50.0)	1(6.25)		8(57.1)	1(7.1)
Risk and treatment received
Standard/intermediate risk	6(42.9)	4(28.6)	0.73	7(43.75)	1(6.25)	1.0	6(42.9)	2(14.3)	0.70
High risk	2(14.3)	2(14.3)		7(43.75)	1(6.25)		5(35.7)	1(7.1)
Time of sample collection from end of treatment
<3 years	3(21.4)	1(7.1)	0.39	5(31.25)	1(6.25)	0.69	4(28.6)	0	0.21
>3 years	5(35.7)	5(35.7)		9(56.25)	1(6.25)		7(50.0)	3(21.4)

Note: p of significance if <0.05.

Table 4. Different studies evaluating seroprotection for measles, mumps, and rubella in ALL patients after the end of treatment.

Study (year)	ALL patients Number (age (range))	Place of study	Study period	Time period after the end of treatment	MMR Protective cutoff titer	Serprotection for MMR (%)	Serconversion after booster vaccination
Our study (2018)	57 patients (age median: 11.50 Y (10.0–15.0 Y)	Jeddah, Saudi Arabia	2014–2017	Median 4.9 Y Range 3.9–7.25 Y	Measles ≥13.5 AU/ml Mumps ≥9 AU/ml Rubella ≥10.0 IU/ml	Measles 75.4% Mumps 71.9% Rubella 75.4%	Measles: 57.1% (8/14 patients) Mumps: 87.5% (14/16 patients) Rubella: 78.6% (11/14 patients) (Booster MMR, response after 6–9 M)
Perkins (2017) [4]	20 patients, 15 ALL (age <21 Y (1.8–17.4 Y))	Minneapolis, USA	2010–2011	6 M	NA	Measles 80% Mumps 50% Rubella 65%	NE
Bochennek (2014) [6]	80 ALL (age <21 Y)	Frankfurt, Germany	2001–2010	12 M	NA	Measles 70.4% Mumps 60.9% Rubella 64.5%	NE
Aytac (2010) [7]	77 ALL	Ankara, Turkey	2004–2008	Median 3.31 Y	Measles and mumps: ratio ≥1.1^a Rubella 15 IU/ml	Measles 42% Mumps 53% Rubella 73.7%	Measles: 55% (20/34 (58.8%) and 2/2 (100%) without and with previous infection history) Mumps:57.1% (15/24 (62.5%) and 5/5 (100%) without and with previous infection history) Rubella: 92.3% (13/20 without infection history) (Booster MMR ± measles)
Zengin (2009) [8]	61 ALL 13 healthy siblings (age median 8.1 Y (5–19 Y))	Kocaeli, Turkey	2006–2008	NA After chemotherapy (also at diagnosis during maintenance)	>11 Virotech Unit	Measles 16.7% (55% at diagnosis 20% in maintenance) controls 38.5%	Measles 70%
Patel (2007) [9]	59 patients 46 ALL	Sutton, United Kingdom	2002–2004	Median 7 M	Measles 120 mIU/ml	Measles 71%	Measles 94% Booster MMR
Ercan (2005) [10]	37 ALL 14 control	Istanbul, Turkey	1999–2001	3–6 M	Measles 0.25 IU/ml Mumps 20 RU/ml Rubella 10 IU/ml	Measles 29% Mumps 29% –	Measles 76% Mumps 66% – (Booster ND)
Brodtman (2005) [11]	99 ALL	New York, USA	NA	Mean 26.4 M	NA	Measles 57% Mumps 55% Rubella 74%	NE
Zignol et al. (2004) [12]	192 patients Hematologic malignancy 85 ALL, 25 HD, 19 NHL	Padua, Italy	1993–1998	15 M (range 0 –72.5 M)	Qualitative assays for measles and mumps. Rubella 15 IU/l	Measles 77% (75/98) Mumps 78% (68/87) Rubella 78% (68/87)	Measles 80% (4/5 patients) Mumps 100% (1 patient) Rubella 100% (5/5 patients) (booster 1 Y after the end of treatment, response after 4 weeks)
Nilsson (2002) [13]	43 ALL (age median 12Y (range: 4–24Y))	Stockholm Sweden	1986–1996	Median 5 Y (range: 4–14 Y)	Measles >0.2 IU/ml – Rubella >10 IU/ml	Measles 60%, – Rubella 72%	Measles 57.1% (8/14 patients) Rubella78.6% (11/14 patients) (1 booster, response after 3 M)
Smith (1995) [14]	13 ALL (age mean 6.2 Y (range 3–16 Y))	New York, USA	NA	Mean 3.7 Y (range, 2–5 Y)	Measles 0.16 U Mumps 1.0 U Rubella 1.0 U	Measles 38% (5/13) Mumps 92% Rubella 92%	Measles 71.4% (5/7) (Booster ND)

Note: ALL: acute lymphoblastic leukemia; HD: Hodgkin’s disease; NHL: non-Hodgkin’s lymphoma; M: month; NE: not evaluated; NA: not available; ND: no details; Y: year

^aCut off at a ratio of the control or patient sample extrication value over value of calibrator (the extinction).

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