Table 2

Cases of dasatinib-induced PAH and their pharmacotherapy.

Study	N of participants/diagnosis	Age, yr/ gender, M or F	Time from dasatinib initiation to PAH diagnosis (mo)	DASA dose, mg/day	Treatment line of DASA	Concomitant PE	Intervention	Improved items
Jose et al. (2017) [64]	1, CML	61, M	26	140	Second	Yes	DASA D/C Tad 20 mg QD and Amb 5 mg daily. The Tad was up-titrated over a period of 4 wk to 40 mg QD, followed by an up titration of Amb to 10 mg QD over the following 4 wk	After 4 mo, mPAP PCWP PVR 6-MWD WHO FC
Ibrahim et al. (2019) [62]	1, CML	46, F	120	70	Second	Yes	DASA D/C Amb 5 mg daily+Tad 20 mg QD	After 1 wk, PAP
Orlandi et al. (2012) [80]	1, CML	53, F	31	100	Second	No	DASA D/C Sil 20 mg TID	After 2 mo, WHO FC PAP 6-MWD
Sano et al. (2012) [81]	1, CML	61, F	27	140	Second	Yes	DASA D/C Sil 60 mg QD	After 1 mo, WHO FC RVSP NT-pro BNP PAP
Wang et al. (2015) [82]	1, CML	33, M	63	100	Second	No	DASA D/C Sil	After 3 mo, PASP
Taçoy et al.(2015) [94]	1, ALL	50, M	24	140	Second	Yes	DASA D/C Bos 62.5 mg BID and in 2 wk increased to 125 mg BID	After 1 mo, NYHA FC After 9 mo, Pro BNP 6-MWD
Groeneveldt et al. (2013) [85]	1, CML	57, M	37	70	Second	No	Sil DASA D/C	The patient did not improve in NYHA FC class by sildenafil and diuretics. 3 mo after substitution DASA with NIL, NYHA FC after start NIL
Nishimori et al. (2018) [86]	1, CML	24, M	48	100	Second	Yes	DASA D/C Sil 20 mg TID+Bos 62.5 mg BID	After 1 mo, WHO FC PAP BNP
Helgeson et al. (2016) [115]	1, CML	30, F	36	NR	Second	Yes	DASA D/C EPO 20 ng kg^-1 min^-1 for 5 mo, then EPO 4 ng kg^-1 min^-1 for 5 mo and discontinuation with mild rebound of MPAP, therefore, Sil was initiated	After 1 wk EPO, Dyspnea
Toya et al. (2019) [104]	1, CML and scleroderma	63, M	36	100	Second	Yes	DASA D/C Tad 40 mg QD+Mac 10 mg QD+Sel 1.2 mg BID	After 1 mo, mPAP PVR 6-MWD
Buchelli et al. (2014) [71]	1, CML	50, M	48	100	Second	Yes	DASA D/C Sil 20 mg TID	After 21 mo, WHO FC RVSP NT-pro BNP mPAP PVR 6-MWD CO CI
Seegobin et al. (2017) [98]	1, CML	52, M	48	NR	Second	Yes	DASA D/C Amb	NR, Symptoms as well as effusions improved
Daccord et al. (2018) [99]	1, CML	32, M	36	NR	Third	Yes	DASA D/C PDE-5 inhibitor+ERA	NR, NYHA FC mPAP 6-MWD PVR CI
Dumitrescu et al. (2011) [83]	1, CML	47, M	72	100	Second	Yes	DASA D/C Sil	After 2 mo, WHO FC PAP CO
Skride et al. (2017) [70]	1, CML	67, M	42	100	Second	Yes	DASA D/C Sil 20 mg TID	NR, mPAP 6-MWD PVR CO
Orlikow et al. (2019) [147]	1, CML	73, F	9	NR	Second	Yes	DASA D/C Nif 30 mg QD	After 12 mo, CO CI PVR
Hennigs et al. (2011) [84]	1, CML	70, M	32	140	Second	Yes	DASA D/C Sil 20 mg TID	After 10 mo, CO RVSP NT-proBNP 6-MWD Mpap WHO FC PVR
Hong et al. (2015) [61]	2, CML	43, M	69	140	Second	Yes	DASAD/C Sil+CCB+Diuretics	NR, NYHA FC PAP RVSP
Hong et al. (2015) [61]	2, CML	52, M	38	140	Second	Yes	DASA D/C Sil 25 mg QD	NR, RVSP BNP 6-MWD
Montani et al. (2012) [15]	3, CML	74, F	33	100	Second	Yes	DASA D/C CCB for 6 mo, then stopped	After 3 mo, NYHA FC, mPAP 6-MWT PVR BNP
		29, F	36	100	Second	Yes	DASA D/C Bos	After 2 mo, NYHA FC After 6 mo, mPAP 6-MWT PVR
		39, F	34	100	Second	Yes	DASA D/C Bos	After 1 mo, NYHA FC

Abbreviations: 6-MWD, 6-minute walk distance; ALL, acute lymphoblastic leukemia; Amb, ambrisentan; BID, two times a day; BNP, b-type natriuretic peptide; Bos, bosentan; CCB, calcium channel blocker; CI, cardiac index; CML, chronic myeloid leukemia; CO, cardiac output; DASA, dasatinib; D/C, discontinuation; EPO, epoprostenol; ERA, endothelin receptor-1 antagonist; F, female; FC, functional classification; M, male; Mac, macitentan; mPAP, mean pulmonary artery pressure; Nif, nifedipine; NIL, nilotinib; NT-pro BNP, N-terminal pro b-type natriuretic peptide; NYHA, New York heart association; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PASP, pulmonary artery systolic pressure; PCWP, pulmonary capillary wedge pressure; PDE-5, phosphodiesterase-5; PE, pulmonary embolism; Pro BNP, pro hormone b-type natriuretic peptide; PVR, pulmonary vascular resistance; QD, once a day; RVSP, right ventricular systolic pressure; Sel, selexipag; Sil, sildenafil; Tad, tadalafil; TID, three times a day; WHO, world health organization; WU, wood unit.

Blood Res 2021;56:229~242 https://doi.org/10.5045/br.2021.2021117