Table 5. Combination therapies for... | American Society of Hematology

Table 5.

Combination therapies for refractory ITP

References	Arms, n	Medication	Dosing	Cycles	Patients, n	Follow-up						Serious treatment complications					Concomitant tx at baseline	Previous treatment failures		Notes
References	Arms, n	Medication	Dosing	Cycles	Patients, n	Reported response	1 mo	3 mo	6 mo	12 mo	24 mo	Kidney, %	Liver, %	Thrombosis, %	Infections, %	Other	Concomitant tx at baseline	Rituximab	TPO	Notes
Pre–TPO-RA era
Figueroa et al⁴⁴	1	Cyclophosphamide	400-650 mg/m² IV, days 1 and 8	3-8	10	CR, 60% (>4, 9, 11, 30, 53, and 126 mo); PR, 20% (>2, >9 mo)	CR, 70%; PR, 20%	CR, 70%; PR, 10%	CR, 60%; PR, 10%	CR, 40%; PR, 0%	CR, 40%; PR, 0%	0	0	10	0	Nausea, alopecia, acne, malaise	No	No	No	2 pts have secondary ITP. ∼10 y follow-up. 2 pts had NR and died of ICH 2 mo later.
		Prednisone	40 mg/m² PO, days 1 and 14
		Vincristine	2 mg IV, days 1 and 8
		Procarbazine or etoposide	100 mg/m² PO, days 1 and 14 or 100 mg/m² IV, days 14-16
Choudhry et al¹¹³	1	Vinblastine	4 mg/m² IV, weekly and then monthly	8 mo	16	CR, 38%; PR, 25% after induction	CR, 38%;PR, 25%		CR, 19%; PR, 6%			0	0	0	0		No	No	No	1 pt had ICH. CR, plt > 150 000; PR, less than twofold increase in plt and >50 000/µL.
Choudhry et al¹¹³	1	Danazol	2-3 mg/kg PO, daily	8 mo	16	Remission in 25% during f/u (6-10 mo)	CR, 38%;PR, 25%		CR, 19%; PR, 6%			0	0	0	0		No	No	No
McMillan⁴⁵	1	Cyclophosphamide	400-650 mg/m² IV, days 1 and 8	3-8	12	CR 42%; PR 8%	CR, 58%; PR, 17%	CR, 58%; PR, 8%	CR, 50%; PR, 8%	CR, 50%; PR, 8%	CR, 50%; PR, 0%	0	0	0	0	Nausea, alopecia, acne, malaise	No	No	No	Follow-up of Figueroa et al.⁴ 3 pts had ICH. CR, plt > 140 000/µL; PR, plt < 50 000/µL.
		Prednisone	40 mg/m² PO, days 1, and 14
		Vincristine	2 mg IV, days 1 and 8
		Procarbazine, or	100 mg/m² PO, days 1 and 14
		Etoposide	100 mg/m² IV, days 14-16
Kappers-Klunne and van’t Veer¹¹⁴	1	Cyclosporine tapered by 50 mg/d every 2 wk	3 mg/kg PO, BID	>4 wk	10	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 20%; PR, 10%	CR, 20%; PR, 0%	CR, 20%; PR, 0%					30% HTN; severe muscle pain, HA, nausea, gum hyperplasia.				CR, plt > 110 000/µL for 12 wk; PR, plt > 40 000/µL for 8 wk. 1 pt required longer CSA to retain CR.
	1	Dosing below 3 mg/kg PO, BID	3 mg/kg PO, BID	>4 wk	10	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 20%; PR, 10%	CR, 20%; PR, 0%	CR, 20%; PR, 0%
	2	CSA	2.5 mg/kg PO BID	<4.5 mo	10	CR, 20% (>2 y, >4 y); PR, 40%			CR, 20%; PR, 40%	CR, 20%	CR, 20%	10
	2	Prednisone	0.4 mg/kg/d	<4.5 mo	10	CR, 20% (>2 y, >4 y); PR, 40%			CR, 20%; PR, 40%	Unclear length of follow-up		10
Williams & Boxer¹¹⁵	1	Vincristine	1.5 mg/m² IV, weekly	2-4 doses	10	80% had PR or CR. Treated pts have been off therapy for a median of 13 mo.	CR, 70%; PR, 0%	CR, 70%; PR, 10%	CR, 70%; PR, 10%	CR, 50%; PR, 10%	CR, 20%; PR, 0%	0	0	0		30% peripheral neuropathy, 30% constipation, 30% jaw pain, 20% alopecia, 40% nausea	Many pts on concomitant tx	No	No	40% Evans syndrome.CR, normal plt after cessation of CSA; PR, plt 80 000-120 000/µL for ≥3 mo while off CSA.
		Methylprednisone	100 mg/m² IV, weekly	2-4 doses
		CSA	5 mg/kg PO, BID	3-6 mo
Boruchov et al⁴⁷	Acute	IVIG	1 g/kg IV		17	66% responded to acute IV therapy.						0	0	6; plt very low at the time.	0		No	No	No	Increase in plt to >30 000/µL to a total count > 50 000/µL
		Anti-D
		Vincristine	0.03 mg/kg IV
		Vinblastine	10 mg IV
	Maintenance	Danazol	10 mg/kg PO		18	Response, 65% at 2 mo and 71% at 4 mo (did not start immunosuppressive therapy in 8 pts with HIV)		65% (11/17)				0	0	0	0	6% ileus	No	No	No
	Maintenance	Azathioprine	2-2.5 mg/kg PO		18			65% (11/17)				0	0	0	0	6% ileus	No	No	No
Hasan et al⁴⁶	1	Second-dose rituximab*	375 mg/m² IV, weekly ×4 weeks	4 wk	20	None with benefit over standard-dose rituximab; 38% responded to R-CVP but short duration; 63% responded to DDR, 4 pts with longer response compared with initial treatment. No pt with NR to initial rituximab responded to DDR.		CR, 50%; PR, 20%	CR, 45%; PR, 20%	CR, 40%; PR, 5%	CR, 5%; PR, 0%	0	0	0	0	13% allergy	No	Yes	No	CR, plt > 150 000/µL for ≥3 mo; PR, plt > 50 000/µL for ≥3 mo.
	2	Rituximab	375 mg/m² IV, weeks 1, 2, 5, and 8	4 infusions	8			CR 38% PR 0%	CR 38% PR 0%	CR 13% PR 0%	CR 0% PR 0%						No	Yes	No
		Cyclophosphamide	750 mg/m² IV, every 4 wk	3
		Vincristine	1.4 mg/m² IV, every 4 wk	3
		Prednisone	100 mg PO, days 1-5, every 4 wk	3
	3	DDR	750 mg/m² IV, weekly	4 wk	8			CR, 50%; PR, 13%	CR, 50%; PR, 13%	CR. 38%; PR, 13%	CR, 0%; PR, 0%						No	Yes	No
Arnold et al⁴⁸	1	Azathioprine	2 mg/kg/d		19	CR, 11%; PR, 63% in a median of 24 mo of follow-up (11.5-46.8 mo); 57% relapsed.						0	0	0	32	16%, gum hypertrophy and tremors.	No	No	No	Response: more than twofold and plt > 30 000/µL for 4 wk. Infections reported to be unrelated to tx.
		CSA	2 mg/kg/d
		MMF	1-2 g/d
Gómez-Almaguer et al¹¹⁶	1	Rituximab	100 mg IV, weekly	4 wk	11	45% achieved CR, 55% achieved PR. Median duration of CR was 46 wk.	CR, 27%; PR, 73%	CR, 36%;PR, 64%	CR, 36%; PR, 55%	CR, 18%; PR, 27%	PR, 0%; CR, 0%	0	0	0	18%, HSV; 36%, UTI	9% died from unclear cause				Patients should have Evans syndrome. CR, plt > 150 000/µL; PR, plt > 50 000/µL on 2 consecutive occasions.
Gómez-Almaguer et al¹¹⁶	1	Alemtuzumab	10 mg SQ, days 1-3	4 wk	11		CR, 27%; PR, 73%	CR, 36%;PR, 64%	CR, 36%; PR, 55%	CR, 18%; PR, 27%	PR, 0%; CR, 0%	0	0	0	18%, HSV; 36%, UTI	9% died from unclear cause
Wang et al¹¹⁷	1	rhTPO	1 µg/kg SQ, daily for 15 d		73	MRR, 38%; TRR, 60%						0	0	0	0	9% visual field defect	Antifibrinolytics	No	No	1 pt had ICH. MRR, plt > 100 000/µL; TRR, plt > 50 000/µL; OR, increase in plt of 30 000/µL and no bleeding.
	1	Danazol	200 mg PO, TID		73	MRR, 38%; TRR, 60%
	2	Danazol	200 mg PO, TID		19	MRR, 8%; TRR, 37%
Cui et al¹¹⁸	1	rhTPO	1 µg/kg SQ daily	14 d	19	Relapse rate: 17.7% at 1 mo, 29.4% at 2 mo, and 29.4% at 3 mo.	Response, 82%	Response, 71%				0	0	0	0		No		No	Response, twofold increase in plt, >30 000/µL and no bleeding. Long-term follow-up 3 mo.
	1	CSA	1.5-2 mg/kg PO, BID	3 mo	19		Response, 82%	Response, 71%
	2b	rhTPO	1 µg/kg SQ, daily	14 d	17	Relapse rate: 50% at 1 mo, 68.8% at 2 mo, and 87.5% at 3 mo.	Response, 50%	Response, 13%
Li et al¹¹⁹	1	CSA	3 mg/kg PO, BID	3-6 mo	45	SR, 37% (59% in CR group and 9% in PR group); 39% relapsed after stopping tx.						0	0	0	0	11% bleeding	No	No	No	CR, plt > 100 000/µL; PR, plt > 30 000/µL and doubled from baseline; SR, plt > 50 000/µL in follow-up. Mean observation period 18 mo.
	1	Prednisone	10-20 mg PO, daily	3-6 mo	45							0	0	0	0	11% bleeding	No	No	No
	2	Rapamycin	6 mg PO, then 2 mg PO, daily	3-6 mo	43	SR, 68% (80% in CR group, 50% in PR group); 24% relapsed after stopping tx.						0	0	0	0	7% bleeding	No	No	2%
	2	Prednisone	10-20 mg PO, daily	3-6 mo	43							0	0	0	0	7% bleeding	No	No	2%
Choi et al⁴⁹	1	Dexamethasone	40 mg PO, days 1-4		20	Response, 60% at 6 mo. Responders had RFS of 92% at 12 mo and 76% at 24 mo.				Response, 55%; CR, 30%		0	0		5	15% HTN	No	Not clear	Not clear	Response defined by Rodeghiero et al.⁹ 5 pts had secondary ITP; 1 pt had AKI 18 mo after tx due to NSAIDs.
		CSA	2.5-3 mg/kg PO, days 1-28							Response, 55%; CR, 30%
		Rituximab	100 mg IV, days 7, 14, 21, and 28
Zhou et al⁵²	1	Rituximab	100 mg IV, weekly	4 wk	77	CR, 45%; OR, 79%; SR, 44%			Response, 67%	Response, 44%	Response, 25%		0		26	1% MI	No	No	8%	1 pt in rituximab/rhTPO group had ICH and died, and 1 pt died from MI with plt count of 26 000/µL.
	1	rhTPO	400 U/kg SQ, initially daily and then weaned depending on plt counts		77	CR, 45%; OR, 79%; SR, 44%			Response, 67%	Response, 44%	Response, 25%		0		26	1% MI	No	No	8%
	2	Rituximab	100 mg IV, weekly	4 wk	38	CR, 23%; OR, 71%; SR, 30%			Response, 54%	Response, 30%	Response, 19%		0	0	21	0%	No	No	5%	CR, plt > 100 000/µL and no bleeding; PR, plt > 30,000/µL and twofold increase from baseline and no bleeding.
Li et al¹²⁰	1	Rituximab	100 mg IV, weekly	4 wk	14	CR, 50%; PR, 43%. Median follow-up 17 mo (range, 3-44 mo).	CR, 50%; PR, 43%	CR, 50%; PR, 43%	CR, 43%; PR, 43%	CR, 43%; PR, 43%	CR, 36%; PR, 43%	0	0	0	7	1 pt died from interstitial pneumonitis. 1 pt died from Aspergillus lower respiratory infection and ICH.	No	No	No	CR, plt ≥ 100 000 and no bleeding; response, plt > 30 000/µL and 2 occurrences of increased plt compared with baseline and no bleeding.
Li et al¹²⁰	1	rhTPO	300 µg/kg/d	14 d		CR, 50%; PR, 43%. Median follow-up 17 mo (range, 3-44 mo).	CR, 50%; PR, 43%	CR, 50%; PR, 43%	CR, 43%; PR, 43%	CR, 43%; PR, 43%	CR, 36%; PR, 43%	0	0	0	7		No	No	No
Mahévas et al⁵⁰	1	Supportive: IVIG, CSA, or no treatment			12	NR				0%	0%			24	40 infection, 3 sepsis		No	Yes	Yes	Response, plt > 100 000/µL or >30 000/µL and doubled from baseline. Pts crossed over from 1 group to the other. No. of pts here represents total no. of pts treated in a specific arm. 7 patients had ICH, 2 pts had HSCT, and 5 pts died.
	2	Immunosuppressants			14	Response, 7%				0%	0%
	3	TPO + immunosuppressants			10	Response, 70% with median follow-up of 15 mo. At end of follow-up, response was 30% (median, 84 mo).
	4	TPO and supportive IVIG/CSA			5	NR				0%	0%
Gudbrandsdottir et al⁵³	1	CSA/MMF, TPO, and IVIG			18						72% (CR + PR)	0				6 HTN				Duration of combination treatment, min 1 mo (mean, 5 mo)
Feng et al⁵⁴	1	Danazol	200 mg PO, BID	16 wk	45	OR, 82% (CR, 38%); 24% relapsed	Response, 47%			Response, 62%		0	0	0		2% serious bleeding, 64% dry skin, 20% HA, 20% GI disorders, 7% HTN	36%	7%	9%	PR, plt > 30 000/µL and at least doubled from baseline; CR, plt > 100 000/µL and no bleeding, without rescue medication at 12-mo follow-up.
	1	ATRA	10 mg PO, BID		45	OR, 82% (CR, 38%); 24% relapsed	Response, 47%			Response, 62%		0	0	0			36%	7%	9%
	2	Danazol	200 mg PO, BID		48	OR, 44% (CR, 8%); 43% relapsed	Response, 15%			Response, 25%		0	2	0		8% serious bleeding, 6% dry skin, 17% HA, 19% GI disorders, 6% HTN.	35%	6%	10%
Wang et al¹²¹	1	Rituximab	100 mg IV, weekly	4 wk	79	CR, 33%; PR, 25%; MR, 14%						3	3		1%	10% dizziness/HA, 15% vomiting				CR, plt > 100 000/µL for 2 mo and no bleeding; PR, plt > 50 000/µL for 2 mo and no bleeding; minimal effective, plt > 20 000/µL for 2 mo and improved bleeding.
	2	Cyclophosphamide	0.8 g IV weekly; 2 mg/kg/d PO	3 mo	86	CR, 13%; PR, 36%; MR, 13%						6	6		3%	14% dizziness/HA, 17% vomiting
	3	Rituximab	100 mg IV, weekly.	4 wk	84	CR, 58%; PR, 17%; MR, 7%						1	1		0%	6% dizziness/HA, 7% vomiting
	3	Cyclophosphamide	0.8 g IV weekly, 2 mg/kg/d PO	3 mo	84	CR, 58%; PR, 17%; MR, 7%						1	1		0%	6% dizziness/HA, 7% vomiting

References	Arms, n	Medication	Dosing	Cycles	Patients, n	Follow-up						Serious treatment complications					Concomitant tx at baseline	Previous treatment failures		Notes
References	Arms, n	Medication	Dosing	Cycles	Patients, n	Reported response	1 mo	3 mo	6 mo	12 mo	24 mo	Kidney, %	Liver, %	Thrombosis, %	Infections, %	Other	Concomitant tx at baseline	Rituximab	TPO	Notes
Pre–TPO-RA era
Figueroa et al⁴⁴	1	Cyclophosphamide	400-650 mg/m² IV, days 1 and 8	3-8	10	CR, 60% (>4, 9, 11, 30, 53, and 126 mo); PR, 20% (>2, >9 mo)	CR, 70%; PR, 20%	CR, 70%; PR, 10%	CR, 60%; PR, 10%	CR, 40%; PR, 0%	CR, 40%; PR, 0%	0	0	10	0	Nausea, alopecia, acne, malaise	No	No	No	2 pts have secondary ITP. ∼10 y follow-up. 2 pts had NR and died of ICH 2 mo later.
		Prednisone	40 mg/m² PO, days 1 and 14
		Vincristine	2 mg IV, days 1 and 8
		Procarbazine or etoposide	100 mg/m² PO, days 1 and 14 or 100 mg/m² IV, days 14-16
Choudhry et al¹¹³	1	Vinblastine	4 mg/m² IV, weekly and then monthly	8 mo	16	CR, 38%; PR, 25% after induction	CR, 38%;PR, 25%		CR, 19%; PR, 6%			0	0	0	0		No	No	No	1 pt had ICH. CR, plt > 150 000; PR, less than twofold increase in plt and >50 000/µL.
Choudhry et al¹¹³	1	Danazol	2-3 mg/kg PO, daily	8 mo	16	Remission in 25% during f/u (6-10 mo)	CR, 38%;PR, 25%		CR, 19%; PR, 6%			0	0	0	0		No	No	No
McMillan⁴⁵	1	Cyclophosphamide	400-650 mg/m² IV, days 1 and 8	3-8	12	CR 42%; PR 8%	CR, 58%; PR, 17%	CR, 58%; PR, 8%	CR, 50%; PR, 8%	CR, 50%; PR, 8%	CR, 50%; PR, 0%	0	0	0	0	Nausea, alopecia, acne, malaise	No	No	No	Follow-up of Figueroa et al.⁴ 3 pts had ICH. CR, plt > 140 000/µL; PR, plt < 50 000/µL.
		Prednisone	40 mg/m² PO, days 1, and 14
		Vincristine	2 mg IV, days 1 and 8
		Procarbazine, or	100 mg/m² PO, days 1 and 14
		Etoposide	100 mg/m² IV, days 14-16
Kappers-Klunne and van’t Veer¹¹⁴	1	Cyclosporine tapered by 50 mg/d every 2 wk	3 mg/kg PO, BID	>4 wk	10	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 20%; PR, 10%	CR, 20%; PR, 0%	CR, 20%; PR, 0%					30% HTN; severe muscle pain, HA, nausea, gum hyperplasia.				CR, plt > 110 000/µL for 12 wk; PR, plt > 40 000/µL for 8 wk. 1 pt required longer CSA to retain CR.
	1	Dosing below 3 mg/kg PO, BID	3 mg/kg PO, BID	>4 wk	10	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 30%; PR, 20%	CR, 20%; PR, 10%	CR, 20%; PR, 0%	CR, 20%; PR, 0%
	2	CSA	2.5 mg/kg PO BID	<4.5 mo	10	CR, 20% (>2 y, >4 y); PR, 40%			CR, 20%; PR, 40%	CR, 20%	CR, 20%	10
	2	Prednisone	0.4 mg/kg/d	<4.5 mo	10	CR, 20% (>2 y, >4 y); PR, 40%			CR, 20%; PR, 40%	Unclear length of follow-up		10
Williams & Boxer¹¹⁵	1	Vincristine	1.5 mg/m² IV, weekly	2-4 doses	10	80% had PR or CR. Treated pts have been off therapy for a median of 13 mo.	CR, 70%; PR, 0%	CR, 70%; PR, 10%	CR, 70%; PR, 10%	CR, 50%; PR, 10%	CR, 20%; PR, 0%	0	0	0		30% peripheral neuropathy, 30% constipation, 30% jaw pain, 20% alopecia, 40% nausea	Many pts on concomitant tx	No	No	40% Evans syndrome.CR, normal plt after cessation of CSA; PR, plt 80 000-120 000/µL for ≥3 mo while off CSA.
		Methylprednisone	100 mg/m² IV, weekly	2-4 doses
		CSA	5 mg/kg PO, BID	3-6 mo
Boruchov et al⁴⁷	Acute	IVIG	1 g/kg IV		17	66% responded to acute IV therapy.						0	0	6; plt very low at the time.	0		No	No	No	Increase in plt to >30 000/µL to a total count > 50 000/µL
		Anti-D
		Vincristine	0.03 mg/kg IV
		Vinblastine	10 mg IV
	Maintenance	Danazol	10 mg/kg PO		18	Response, 65% at 2 mo and 71% at 4 mo (did not start immunosuppressive therapy in 8 pts with HIV)		65% (11/17)				0	0	0	0	6% ileus	No	No	No
	Maintenance	Azathioprine	2-2.5 mg/kg PO		18			65% (11/17)				0	0	0	0	6% ileus	No	No	No
Hasan et al⁴⁶	1	Second-dose rituximab*	375 mg/m² IV, weekly ×4 weeks	4 wk	20	None with benefit over standard-dose rituximab; 38% responded to R-CVP but short duration; 63% responded to DDR, 4 pts with longer response compared with initial treatment. No pt with NR to initial rituximab responded to DDR.		CR, 50%; PR, 20%	CR, 45%; PR, 20%	CR, 40%; PR, 5%	CR, 5%; PR, 0%	0	0	0	0	13% allergy	No	Yes	No	CR, plt > 150 000/µL for ≥3 mo; PR, plt > 50 000/µL for ≥3 mo.
	2	Rituximab	375 mg/m² IV, weeks 1, 2, 5, and 8	4 infusions	8			CR 38% PR 0%	CR 38% PR 0%	CR 13% PR 0%	CR 0% PR 0%						No	Yes	No
		Cyclophosphamide	750 mg/m² IV, every 4 wk	3
		Vincristine	1.4 mg/m² IV, every 4 wk	3
		Prednisone	100 mg PO, days 1-5, every 4 wk	3
	3	DDR	750 mg/m² IV, weekly	4 wk	8			CR, 50%; PR, 13%	CR, 50%; PR, 13%	CR. 38%; PR, 13%	CR, 0%; PR, 0%						No	Yes	No
Arnold et al⁴⁸	1	Azathioprine	2 mg/kg/d		19	CR, 11%; PR, 63% in a median of 24 mo of follow-up (11.5-46.8 mo); 57% relapsed.						0	0	0	32	16%, gum hypertrophy and tremors.	No	No	No	Response: more than twofold and plt > 30 000/µL for 4 wk. Infections reported to be unrelated to tx.
		CSA	2 mg/kg/d
		MMF	1-2 g/d
Gómez-Almaguer et al¹¹⁶	1	Rituximab	100 mg IV, weekly	4 wk	11	45% achieved CR, 55% achieved PR. Median duration of CR was 46 wk.	CR, 27%; PR, 73%	CR, 36%;PR, 64%	CR, 36%; PR, 55%	CR, 18%; PR, 27%	PR, 0%; CR, 0%	0	0	0	18%, HSV; 36%, UTI	9% died from unclear cause				Patients should have Evans syndrome. CR, plt > 150 000/µL; PR, plt > 50 000/µL on 2 consecutive occasions.
Gómez-Almaguer et al¹¹⁶	1	Alemtuzumab	10 mg SQ, days 1-3	4 wk	11		CR, 27%; PR, 73%	CR, 36%;PR, 64%	CR, 36%; PR, 55%	CR, 18%; PR, 27%	PR, 0%; CR, 0%	0	0	0	18%, HSV; 36%, UTI	9% died from unclear cause
Wang et al¹¹⁷	1	rhTPO	1 µg/kg SQ, daily for 15 d		73	MRR, 38%; TRR, 60%						0	0	0	0	9% visual field defect	Antifibrinolytics	No	No	1 pt had ICH. MRR, plt > 100 000/µL; TRR, plt > 50 000/µL; OR, increase in plt of 30 000/µL and no bleeding.
	1	Danazol	200 mg PO, TID		73	MRR, 38%; TRR, 60%
	2	Danazol	200 mg PO, TID		19	MRR, 8%; TRR, 37%
Cui et al¹¹⁸	1	rhTPO	1 µg/kg SQ daily	14 d	19	Relapse rate: 17.7% at 1 mo, 29.4% at 2 mo, and 29.4% at 3 mo.	Response, 82%	Response, 71%				0	0	0	0		No		No	Response, twofold increase in plt, >30 000/µL and no bleeding. Long-term follow-up 3 mo.
	1	CSA	1.5-2 mg/kg PO, BID	3 mo	19		Response, 82%	Response, 71%
	2b	rhTPO	1 µg/kg SQ, daily	14 d	17	Relapse rate: 50% at 1 mo, 68.8% at 2 mo, and 87.5% at 3 mo.	Response, 50%	Response, 13%
Li et al¹¹⁹	1	CSA	3 mg/kg PO, BID	3-6 mo	45	SR, 37% (59% in CR group and 9% in PR group); 39% relapsed after stopping tx.						0	0	0	0	11% bleeding	No	No	No	CR, plt > 100 000/µL; PR, plt > 30 000/µL and doubled from baseline; SR, plt > 50 000/µL in follow-up. Mean observation period 18 mo.
	1	Prednisone	10-20 mg PO, daily	3-6 mo	45							0	0	0	0	11% bleeding	No	No	No
	2	Rapamycin	6 mg PO, then 2 mg PO, daily	3-6 mo	43	SR, 68% (80% in CR group, 50% in PR group); 24% relapsed after stopping tx.						0	0	0	0	7% bleeding	No	No	2%
	2	Prednisone	10-20 mg PO, daily	3-6 mo	43							0	0	0	0	7% bleeding	No	No	2%
Choi et al⁴⁹	1	Dexamethasone	40 mg PO, days 1-4		20	Response, 60% at 6 mo. Responders had RFS of 92% at 12 mo and 76% at 24 mo.				Response, 55%; CR, 30%		0	0		5	15% HTN	No	Not clear	Not clear	Response defined by Rodeghiero et al.⁹ 5 pts had secondary ITP; 1 pt had AKI 18 mo after tx due to NSAIDs.
		CSA	2.5-3 mg/kg PO, days 1-28							Response, 55%; CR, 30%
		Rituximab	100 mg IV, days 7, 14, 21, and 28
Zhou et al⁵²	1	Rituximab	100 mg IV, weekly	4 wk	77	CR, 45%; OR, 79%; SR, 44%			Response, 67%	Response, 44%	Response, 25%		0		26	1% MI	No	No	8%	1 pt in rituximab/rhTPO group had ICH and died, and 1 pt died from MI with plt count of 26 000/µL.
	1	rhTPO	400 U/kg SQ, initially daily and then weaned depending on plt counts		77	CR, 45%; OR, 79%; SR, 44%			Response, 67%	Response, 44%	Response, 25%		0		26	1% MI	No	No	8%
	2	Rituximab	100 mg IV, weekly	4 wk	38	CR, 23%; OR, 71%; SR, 30%			Response, 54%	Response, 30%	Response, 19%		0	0	21	0%	No	No	5%	CR, plt > 100 000/µL and no bleeding; PR, plt > 30,000/µL and twofold increase from baseline and no bleeding.
Li et al¹²⁰	1	Rituximab	100 mg IV, weekly	4 wk	14	CR, 50%; PR, 43%. Median follow-up 17 mo (range, 3-44 mo).	CR, 50%; PR, 43%	CR, 50%; PR, 43%	CR, 43%; PR, 43%	CR, 43%; PR, 43%	CR, 36%; PR, 43%	0	0	0	7	1 pt died from interstitial pneumonitis. 1 pt died from Aspergillus lower respiratory infection and ICH.	No	No	No	CR, plt ≥ 100 000 and no bleeding; response, plt > 30 000/µL and 2 occurrences of increased plt compared with baseline and no bleeding.
Li et al¹²⁰	1	rhTPO	300 µg/kg/d	14 d		CR, 50%; PR, 43%. Median follow-up 17 mo (range, 3-44 mo).	CR, 50%; PR, 43%	CR, 50%; PR, 43%	CR, 43%; PR, 43%	CR, 43%; PR, 43%	CR, 36%; PR, 43%	0	0	0	7		No	No	No
Mahévas et al⁵⁰	1	Supportive: IVIG, CSA, or no treatment			12	NR				0%	0%			24	40 infection, 3 sepsis		No	Yes	Yes	Response, plt > 100 000/µL or >30 000/µL and doubled from baseline. Pts crossed over from 1 group to the other. No. of pts here represents total no. of pts treated in a specific arm. 7 patients had ICH, 2 pts had HSCT, and 5 pts died.
	2	Immunosuppressants			14	Response, 7%				0%	0%
	3	TPO + immunosuppressants			10	Response, 70% with median follow-up of 15 mo. At end of follow-up, response was 30% (median, 84 mo).
	4	TPO and supportive IVIG/CSA			5	NR				0%	0%
Gudbrandsdottir et al⁵³	1	CSA/MMF, TPO, and IVIG			18						72% (CR + PR)	0				6 HTN				Duration of combination treatment, min 1 mo (mean, 5 mo)
Feng et al⁵⁴	1	Danazol	200 mg PO, BID	16 wk	45	OR, 82% (CR, 38%); 24% relapsed	Response, 47%			Response, 62%		0	0	0		2% serious bleeding, 64% dry skin, 20% HA, 20% GI disorders, 7% HTN	36%	7%	9%	PR, plt > 30 000/µL and at least doubled from baseline; CR, plt > 100 000/µL and no bleeding, without rescue medication at 12-mo follow-up.
	1	ATRA	10 mg PO, BID		45	OR, 82% (CR, 38%); 24% relapsed	Response, 47%			Response, 62%		0	0	0			36%	7%	9%
	2	Danazol	200 mg PO, BID		48	OR, 44% (CR, 8%); 43% relapsed	Response, 15%			Response, 25%		0	2	0		8% serious bleeding, 6% dry skin, 17% HA, 19% GI disorders, 6% HTN.	35%	6%	10%
Wang et al¹²¹	1	Rituximab	100 mg IV, weekly	4 wk	79	CR, 33%; PR, 25%; MR, 14%						3	3		1%	10% dizziness/HA, 15% vomiting				CR, plt > 100 000/µL for 2 mo and no bleeding; PR, plt > 50 000/µL for 2 mo and no bleeding; minimal effective, plt > 20 000/µL for 2 mo and improved bleeding.
	2	Cyclophosphamide	0.8 g IV weekly; 2 mg/kg/d PO	3 mo	86	CR, 13%; PR, 36%; MR, 13%						6	6		3%	14% dizziness/HA, 17% vomiting
	3	Rituximab	100 mg IV, weekly.	4 wk	84	CR, 58%; PR, 17%; MR, 7%						1	1		0%	6% dizziness/HA, 7% vomiting
	3	Cyclophosphamide	0.8 g IV weekly, 2 mg/kg/d PO	3 mo	84	CR, 58%; PR, 17%; MR, 7%						1	1		0%	6% dizziness/HA, 7% vomiting

Long-term follow-up may be low because patients relapsed or because of the small number of patients at the specific time point.

AKI, acute kidney injury; ATRA, all-trans retinoic acid; BID, twice a day; CSA, cyclosporine A; DDR, double the standard dose rituximab; f/u, follow-up; GI, gastrointestinal; HA, headache; HSCT, hematopoietic stem cell transplant; HSV, herpes simplex virus; HTN, hypertension; ICH, intracranial hemorrhage; MI, myocardial infarction; min, minimum; MMF, mycophenolate mofetil; MRR, major response rate; NSAID, nonsteroidal anti-inflammatory drug; OR, overall response; plt, platelets; PO, by mouth; pt/pts, patient/patients; R-CVP, rituximab, cyclophosphamide, vincristine, and prednisone; RFS, relapse-free survival; rhTPO, recombinant human TPO; SQ, subcutaneous; SR, sustained response; TID, 3 times a day; TRR, total response rate; tx, treatment; UTI, urinary tract infection.

With the addition of immunosuppressive therapy.

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