Table 2. Immunosuppression, GvHD and outcome following CSA-related neurotoxicity.

Patient no.	Immune suppression post CSA toxicity	Interval before re-starting CSA/TAC	Maximum GvHD pre CSA toxicity acute and chronic	Evolution of GvHD post CSA neurotoxicity		Outcome/follow-upa cause death/current complications
				Acute/late acute	Chronic
1	TACb, CS, mAb	219	Grade II skin, extensive chronic skin, mouth	Nil	Progressed to extensive skin, mouth and lung	Alive +7.8 years	Extensive bronchiolitis obliterans
2	CS, MMF	NA	Grade I skin	Progressed to Grade II skin	Developed limited skin	Alive +12.1 years	GvHD resolved
3	CSA/TACc, CS	20	Grade IV skin and gut	Grade IV skin, gut recurred	Developed extensive skin	Alive +10.3 years	Extensive vitiligo, epilepsy following PRES needing treatment with anti-epileptics
4	Nil	NA	Grade I skin	Grade I skin recurred	Nil	Alive +8.1 years
5	TAC, CS	132	Nil	Developed Grade III skin, liver	Developed extensive skin, lung	Alive +5.9 years	Bronchiolitis obliterans, bilateral avascular necrosis of the hip
6	TAC, CS, MMF, Siro, mAb, MSC	597	Grade IV skin, gut	Grade IV skin, gut persisted	Developed limited skin, liver	Deceased +1.8 years	Liver GvHD
7	TACc, CS, MMF, mAb	228	Nil	Developed Grade IV skin, gut	Developed extensive skin, gut, liver	Deceased +293 days	Bronchiolitis obliterans/infection
8	CSA/TACc, CS, MMF, MTX, mAb	2	Grade IV skin, gut, extensive chronic skin/gut	Nil	Progressed to extensive skin, gut, liver	Deceased +1.2 years	GvHD, infection (E. coli sepsis, pulmonary Aspergillosis)
9	TAC, CS	0	Grade IV skin, gut, liver	Grade IV skin, gut, liver persisted	NE	Deceased +68 days	Infection, TMA
10	CS, MMF	NA	Nil	Developed Grade II gut	Developed limited gut	Deceased +1.6 years	Acute liver necrosis, presumed infection
11	CSAc, CS, MMF, Siro	3	Grade II skin	Progressed to Grade III skin	NEd	Deceased +275 days	Bone marrow aplasia, fungal chest infection, CMV/adeno/HHV6 viraemia
12	CSAe, CS, MMF	10	Nil	Developed Grade II skin	Developed limited skin	Alive +10.4 years	GvHD resolved
13	CS, MMF, mAb	NA	Grade II skin, limited chronic skin	Progressed to Grade IV gut	Limited skin persisted. Developed extensive gut	Alive +7.8 years	GvHD resolved
14	CS, Siro, mAb, MSC	NA	Grade IV skin and gut	Grade IV gut persisted	Developed extensive gut	Alive +6.2 years	GvHD resolved
15	TAC, CS	30	Grade 1 skin	Progressed to Grade IV skin, gut	Developed extensive skin, gut	Deceased +298 days	GvHD, infection (RSV pneumonitis)
16	CSA/TACc, CS, mAb, MSC	4	Grade III skin, gut	Progressed to Grade IV skin, gut, liver	Developed extensive skin, gut, liver	Deceased +253 days	GvHD/infection
17	CSA, CS, MMF, mAb, ATG, MSC	1	Grade IV skin	Grade IV skin persisted Developed Grade IV gut	NE	Deceased +66 days	GvHD, pulmonary haemorrhage
18	CS, MMF, mAb	NA	Grade I gut	Progressed to Grade III skin, gut	Developed extensive skin, gut	Deceased +1.9 years	GvHD
19	TACc, CS, MMF, mAb	0	Grade III skin, gut, liver, extensive chronic skin, gut, liver	Nil	extensive skin, gut, liver persisted	Deceased +1.9 years	Infection (Influenza pneumonitis)
20	CSAc, CS, Siro mAb	12	Grade III skin, gut, extensive chronic skin, gut	Grade III skin, gut recurred	Progressed to extensive skin, gut, liver	Deceased +304 days	GvHD, infection (adenoviraemia)
21	CSAc, CS	4	Nil	Nil	Nil	Deceased +5.2 years	Pulmonary fibrosis
22	TAC, CS, MMF	343	Grade IV skin, gut	Nil	Developed extensive skin, gut	Alive +10.3 years	Extensive vitiligo
23	CS, MMF	NA	Nil	Developed Grade I skin	Nil	Alive +5.5 years	GvHD resolved
24	CS, MMF, Siro	NA	Nil	Nil	Nil	Deceased +125 days	Pulmonary vasculopathy, infection
25	CSA/TAC, CS, MMF, mAb	5	Nil	Developed Grade IV skin, gut	Developed extensive gut, liver	Deceased +1.6 years	Infection
26	CSA, CS	20	Nil	Developed Grade I skin	Nil	Alive +7.9 years	GvHD resolved

Abbreviations: CS=corticosteroids; CSA=cyclosporine; mAb=monoclonal antibodies including infliximab, daclizumab and/or basiliximab; MMF=mycophenolate mofetil; MSC=mesenchymal stem cells; MTX=methotrexate; NA=not applicable; NE=not evaluable; RSV=respiratory syncytial virus; Siro=sirolimus; TAC=Tacrolimus.

^aAs of 1 April 2016 except for patient #22 for whom last follow-up was 27 September 2012.

^bTacrolimus started to assess if tolerated in context of potential lung transplantation.

^cCSA and/or Tacrolimus restarted but not tolerated.

^dNE as received second HSCT.

^eCSA continued with clobazam.