Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis: A systematic review with meta-analysis

Table 1 Methodological quality and risk of bias assessment of the included studies (n = 17)

Randomized controlled trial
			Ref.	Randomization process	Deviation from the intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported result	Overall Bias
			Moore et al[13]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Prospective studies
	Ref.			A clearly stated aim	Inclusion of consecutive patients	Prospective collection of data	Endpoints appropriate to the aim of the study	Unbiased assessment of the study endpoint	Follow-up period appropriate to the aim of the study	Loss to follow up less than 5%	Prospective calculation of the study size
	Tyndall et al[29]			1	1	2	2	2	1	2	1
	Burt et al[26]			2	2	2	1	2	1	2	1
	Burt et al[25]			2	2	2	1	2	1	2	1
	Verburg et al[30]			2	2	2	2	2	2	2	1
	Snowden et al[27]			2	2	2	1	2	1	2	1
	van Laar et al[28]			2	2	2	2	2	2	2	1
	Snowden et al[15]			1	1	2	1	2	1	2	1
	Bingham et al[11]			2	2	2	2	2	2	2	1
	Teng et al[9]			2	2	2	2	2	2	2	1
	Pavletic et al[31]			2	2	2	2	2	2	2	1
	Verburg et al[32]			2	2	2	2	2	2	2	1
Case reports
		Ref.		Selection score	Ascertainment score	Causality score	Reporting score	Total score
		Silva et al[12]		1	2	1	1	5
		Joske et al[33]		1	1	1	1	4
		Kim et al[35]		1	2	1	1	5
		Durez et al[34]		1	1	1	1	4
		Burt et al[36]		1	2	1	1	5

Table 2 General characteristics of the included studies (n = 17)

Sl. No	Ref.	Year	Study design	Indication	Sample size	Age (yr)	Source (Autologous/allogenic)	Mean follow-up (mo)
1	Joske et al[33]	1997	Case report	Failed DMARDs	1	46	Autologous	6
2	Durez et al[34]	1998	Case report	Failed DMARDs	1	22	Autologous	10
3	Burt et al[26]	1998	Prospective study	Failed DMARDs	2	44	Autologous	12
4	Snowden et al[27]	1999	Prospective study	Failed DMARDs	8	18-65	Autologous	18
5	Burt et al[25]	1999	Prospective study	Failed DMARDs	4	46.2	Autologous	12
6	Kim et al[35]	2002	Case report	Failed DMARDs	1	54	Autologous	6
7	Tyndall et al[29]	2001	Prospective study	Primary treatment	43	NR	Autologous	11
8	van Laar et al[28]	2001	Prospective study	Failed DMARDs	8	18-60	Autologous	18
9	Verburg et al[30]	2001	Prospective study	Failed DMARDs	14	43	Autologous	12
10	Bingham et al[11]	2001	Prospective study	Failed DMARDs	6	37.33	Autologous	20
11	Pavletic et al[31]	2001	Prospective study	Failed DMARDs	6	42.5	Autologous	26.5
12	Moore et al[13]	2001	RCT	Failed DMARDs	33	18-65	Autologous	12
13	Burt et al[36]	2004	Case report	Failed DMARDs	1	52	Allogenic	12
14	Snowden et al[15]	2004	Prospective study	Failed DMARDs	73	42	Autologous	18
15	Verburg et al[32]	2005	Prospective study	Failed DMARDs	8	35-55 years	Autologous	24
16	Teng et al[9]	2005	Prospective study	Failed DMARDs	8	43	Allogenic	60
17	Silva et al[12]	2018	Retrospective study	Failed DMARDs (10), failed autologous HSCT (1), secondary haemophagocytic lymphohistiocytosis (5)	16	12	Allogenic	29

DMARDs: Disease modifying anti-rheumatic drugs; HSCT: Haematopoietic stem cell transplant; NR: Not reported; RCT: Randomised controlled trial.

Table 3 Hematopoietic stem cell transplant protocol in the included studies (n = 17)

Sl. No	Ref.	Mobilization regimen	Graft manipulation	HSC selection	Conditioning regimen
1	Joske et al[33]	CYC 4 g/m2, G-CSF 10 µg/kg	Leukapheresis	CD 34 +ve selection	CYC 200mg/kg
2	Durez et al[34]	CYC 1.5 g/m2, etoposide 300 mg/m2, G-CSF 5 µg/kg	Leukapheresis	CD 34 +ve selection	CYC 60 mg daily and busulfan 4 mg daily
3	Burt et al[26]	CYC, G-CSF	Leukapheresis	CD 34 +ve selection	CYC 200 mg/kg, ATG 90 mg/kg
4	Snowden et al[27]	CYC 100-200 mg/kg, G-CSF 5 µg/kg	Leukapheresis	CD34 +ve selection	CYC 100 mg/kg or 200 mg/kg
5	Burt et al[25]	CYC 2 g/m2, G-CSF	Leukapheresis	CD34 +ve selection	CYC 200 mg/kg, ATG 90 mg/kg
6	Kim et al[35]	CYC 4 g/m², G-CSF 5 µg/kg	Leukapheresis	CD 34 +ve selection	CYC 200 mg/kg, ATG 90 mg/kg
7	Tyndall et al[29]	CYC, G-CSF	Leukapheresis	NR	CYC 200 mg/kg, ± ATG 90 mg/kg, ± Busulfan
8	van Laar et al[28]	CYC 4 g/m², G-CSF 10 µg/kg	Leukapheresis	CD34 +ve selection	CYC 200 mg/kg
9	Verburg et al[30]	CYC 4 g/m², G-CSF 10 µg/kg	Leukapheresis	CD 34 +ve selection	CYC 200 mg/kg
10	Bingham et al[11]	CYC 2 g/m2, G-CSF	Leukapheresis	CD 34 +ve selection	CYC 200 mg/kg
11	Pavletic et al[31]	CYC 2 g/m2, G-CSF	Leukapheresis	CD34 +ve selection	CYC 200 mg/kg, ATG 90 mg/kg
12	Moore et al[13]	CYC 200 mg/kg, G-CSF 10 µg/kg	Leukapheresis	CD34 +ve selection (18) / No selection (15)	CYC 200 mg/kg
13	Burt et al[36]	NA	NA	CD 34 +ve selection	CYC 150 mg/kg, fludarabine 125 mg/m2, alemtuzumab 20 mg
14	Snowden et al[15]	CYC 200 mg/kg, G-CSF 5- 10 µg/kg	Leukapheresis	CD 34 +ve selection (45) / No selection (28)	CYC 200 mg/kg
15	Verburg et al[32]	CYC 200 mg/kg, G-CSF	Leukapheresis	CD 34 +ve selection	CYC 200 mg/kg
16	Teng et al[9]	NA	NA	CD 34 +ve selection	CYC 200 mg/kg
17	Silva et al[12]	NA	NA	CD 34 +ve selection	Fludarabine 30 mg/m²/d, melphalan 140 mg/m²/d, alemtuzumab 0.2 mg/kg/d or fludarabine 30 mg/m²/d, treosulfan 14 mg/m²/d, alemtuzumab 0.2 mg/kg/d

ATG: Anti-thymocyte globulin; CD: Cluster differentiation: CYC: Cyclophosphamide; G-CSF: Granulocyte colony stimulating factor; HSC: Hematopoietic stem cell; NA: Not applicable; NR: Not reported.