Hematopoietic Stem Cell Therapy for Wiskott–Aldrich Syndrome: Improved Outcome and Quality of Life

Figures & data

Table 1 Scoring System to Define Clinical Phenotypes Associated with Mutations in the WAS Gene

Clinical Phenotype	XLN	iXLT	XLT.		Classic WAS
Score	0	<1	1	2	3	4	5
Clinical/laboratory findings
Thrombocytopenia	–	–/+	+	+	+	+	+
Small platelets	–	+	+	+	+	+	+
Eczema	–	–	–	(+)	+	++	–/(+)/+/++
Immunodeficiency	–/(+)	–	–/(+)	(+)	+	+	(+)/+
Infections	–/(+)	–	–	(+)	+	+/++	–/(+)/+/++
Autoimmunity and/or malignancy	–	–	–	–	–	–	+
Congenital neutropenia	+	–	–	–	–	–	–
Myelodysplasia	–/+	–	–	–	–	–	–

Notes: Scoring system: –/(+), absent or mild; –/+, intermittent thrombocytopenia, possible myelodysplasia; (+), mild, transient eczema or mild, infrequent infections not resulting in sequelae; +, thrombocytopenia, persistent but therapy-responsive eczema, and recurrent infections requiring antibiotics and often intravenous immunoglobulin prophylaxis; ++, eczema that is difficult to control and severe, life-threatening infections. Reproduced with permission from Albert MH, Notarangelo LD, Ochs HD. Clinical spectrum, pathophysiology and treatment of the Wiskott–Aldrich syndrome. Curr Opin Hematol. 2011;18(1):42–48.³⁰ Copyright © 2011, Wolters Kluwer Health.

Abbreviations: WAS, Wiskott–Aldrich syndrome; XLN, X-linked neutropenia; XLT, X-linked thrombocytopenia; iXLT, intermittent XLT.

Table 2 Allogeneic HSCT for WAS: Evolution of Long-Term Outcomes

	Donor Sources (n)	Overall Survival	Graft Rejection	Acute GvHD	Chronic GvHD	Post-HSCT Autoimmunity	Mixed Chimerism
Filipovich et al^Citation46 1968–1996 N=170	MSD (55) MRD (3) MMRD (59) MUD (43) MMUD (19)	70% MSD-87% Other RD-52% UD-71%	9%	Grade II–IV: MSD- 34% Other RD- 30% UD-56% grade III–IV: NR	21%	NR	NR
Ozsahin et al^Citation48 1979–2001 N= 96	MSD (45) MMRD (19) MUD (32)	96% EFS 75% <2 yo: 84% ≥2 yo: 68%	NR	NR	7%	20%	18% with mixed chimerism Associated with post-HSCT autoimmunity
Moratto et al^Citation47 1980–2009 N=194	MSD (39) MRD (1) MMRD (35) MUD (91) UCB (24)	84% <5 yo: 91.9% ≥5 yo: 73.3%	7%	Grade II–IV: NR grade III–IV: 11.3%	14.8%	13.9%	27.9% in at least one cell lineage Associated with post-HSCT autoimmunity
Shin et al^Citation67 1990–2009 N=47	MSD (6) MRD (1) MMRD (1) MUD (17) MMUD (14) UCB (8)	80%	8.5%	Grade II–IV: 40% grade III–IV: 23%	21%	55%	No association with post-HSCT autoimmunity
Elfeky et al^Citation49 1996–2016 N=34	MSD (7) MMRD (3) MUD (20) MMUD (1) UCB (3)	100%	6%	Grade II–IV: 26% grade III–IV: NR	3%	20%	No association with post-HSCT autoimmunity
Ngwube et al^Citation50 2004–2016 N=12	MRD (4) MUD (5) MMUD (3)	92%	25%	Grade II–IV: 16.7% grade III–IV: NR	0%	25%	42% with mixed chimerism
Burroughs et al^Citation33 2005–2015 N=129	MSD (22) MMRD (2) MUD (41) MMUD (21) UCB (39)	91% <5 yo: 94% ≥5 yo: 66%	4.7%	Grade II–IV: 27% grade III–IV: 15%	17%	14%	No association with post-HSCT autoimmunity
Shekhovtsova et al^Citation53 1996–2013 N=90	UCB (90)	75% >2 yo: HR 2.61	11%	Grade II–IV: 38% grade III–IV: 14%	17%	NR	24% with mixed chimerism
Balashov et al^Citation62 2012–2016 N=34	MUD (18) Haplo (16)	93.8% EFS Historical group: 50% GCSF group: 93.8%	30.3% in historical group 0% in GCSF/plerixafor group	Grade II–IV: 26.8% grade III–IV: 0%	6%	NR	50% with mixed chimerism in historical group No patients with mixed chimerism in the GCSF/plerixafor group
Yue et al^Citation55 2015–2017 N= 5	Haplo (5)	100%	0%	Grade I: 40% grade II–IV: 0%	20%	NR	No patients with mixed chimerism

Abbreviations: EFS, event-free survival; GvHD, graft-vs-host disease; Haplo, haploidentical; HSCT, hematopoietic stem cell transplantation; HR, hazard ratio; MRD, matched related donor; MMRD, mismatched related donor; MMUD, mismatched unrelated donor; MSD, matched sibling donor; MUD, matched unrelated donor; NR, not reported; RD, related donor; UCB, umbilical cord blood.

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