Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience

Table 1 Demographics and orthotopic heart transplantation outcomes

AL-OHT	M/F	Age at OHT	List to OHT (d)	Year OHT	PO FU (yr)	Major outcomes
8	F	52	62	1997	16.5	Alive, doing well
22	F	53	1160	2011	3.9	Alive, PTLD in remission, VGPR on bortezomib
23	M	58	13	2011	3.1	Alive, doing well
1	M	45	86	1992	14.1	Died, progressive amyloid; renal transplantation 53 mo post OHT
17	F	51	94	2003	10.8	Died, renal failure, debility; hematologic relapse and renal amyloid
9	M	56	16	1998	8.6	Died, metastatic melanoma
2	M	44	126	1993	8.4	Died, PTLD, sepsis, progressive amyloidosis
12	F	57	44	1999	8.2	Died, cardiogenic shock secondary to cardiac amyloid, required dialysis for renal amyloid post ASHCT#2
3	M	56	14	1994	7.5	Died, progressive amyloid
14	M	33	30	1999	6.3	Died, cardiac allograft vasculopathy
16	F	53	33	2000	5.4	Died, progressive GI amyloid and stroke; renal transplant 23 mo post-op
7	M	61	415	1997	3.5	Died, progressive amyloid autonomic and peripheral neuropathy
18	M	56	33	2004	3.1	Died, complications of myelodysplastic syndrome
5	F	47	68	1995	2.6	Died, PTLD, progressive multifocal leukoencephalopathy
10	F	54	5	1998	2.2	Died, progressive amyloid
19	M	62	18	2005	2.1	Died, progressive amyloid peripheral neuropathy and GI involvement, recurrent pneumonia
4	M	49	86	1994	1.2	Died, progressive amyloid
21	F	51	29	2007	1.2	Died, progressive GI amyloid, right heart failure, renal failure, steroid myopathy vs amyloid neuropathy
13	F	51	103	1999	0.9	Died, sepsis, multiorgan failure after AHSCT
11	F	48	31	1999	0.7	Died, disseminated fungal infection after AHSCT
15	F	60	33	1999	0.6	Died, progressive amyloid peripheral and autonomic neuropathy
20	F	52	33	2006	0.6	Died, progressive amyloid and overwhelming infection
6	M	56	99	1996	0.04	Died, refractory rejection; had combined renal and cardiac transplant
Median (IQR)		53 (33, 62)	33 (29, 94)

The first three rows are alive. M: Male; F: Female; PO FU: Post-operative follow-up; PTLD: Post-transplant lymphoproliferative disorder; GI: Gastrointestinal; VGPR: Very good partial response; IQR: Interquartile range.

Table 2 Baseline disease burden

AL-OHT	IFE positive	g/dL	dFLC (mg/L)	Tx mBMI, kg g/L m2	Creatinine (mg/dL)	Alkaline phosphatase (U/L)	IVS (mm)	EF (%)	BM PC (%)
8	Yes			688	0.9	115	15	33	12
22	Yes	1.6	298	977	0.8	60	14	55	18
23	NA	0	1059	951	1.5	150	15	50	10
1	Yes			1120	1.4	112	16	40	8
17	Yes	0	70	913	0.9	302	16	64	12
9	Yes	0	271	822	1.7	334	12	78	8
2	Yes			1191	1.1	130	15	60	5
12	Yes	0		742	1.2	312	17	30	13
3	NA			729	1.2		18	56	20
14	Yes			620	0.9	207	16	20	12
16	No	0		402	1.1	145	12	53	15
7	No				1.2	132	15	57	6
18	Yes	0	245	935	1.2	90	18	56	17
5	No			599	0.9	428	22	40	4
10	Yes	0		629	0.7	110	16	44	5
19	Yes	0	304	744	1.1	90	16	24	12
4	NA			693	1.1		14	20	NA
21	Yes	1.9	138	632	0.9	70	13	43	13
13	Yes	0.14		779	1.0	312	16	40	5
11	Yes	0	279	513	0.7	156	21	30	12
15	Yes			788	1.2	118	17	50	9
20	Yes	0	87	865	1.5	112	14	40	7
6	Yes			894	1.1	229	13	35	19
Median (IQR)			27 (11-30)	761 (631, 919)	1.1 (0.9, 1.2)	132 (111, 267)	15 (14, 16)	40 (34, 56)	12 (7, 13)

The first three rows are alive. IFE: Immunofixation of serum and/or urine; dFLC: Difference between involved and uninvolved immunoglobulin free light chains; Tx: Transplant; mBMI: Modified body mass index [albumin × weight/(height)²]; IVS: Interventricular septum; EF: Ejection fraction; BM PC: Bone marrow plasma cells; NA: Not available; IQR: Interquartile range.

Table 3 Chemotherapy and response

AL-OHT	Rx relative to OHT	First amyloid directed therapy (Rx)	Response to1st Rx	Lines of Rx
8	Only Rx post-OHT	AHSCT1	CR	1
22	Rx pre- and post-OHT	Mel-Dex	CR	≥ 2
23	Rx pre- and post-OHT	Bortezomib-Dex3	VGPR	≥ 2
1	Only Rx post-OHT	Mel-Pred	CR	≥ 2
17	Only Rx post-OHT	AHSCT1	CR	≥ 2
9	Only Rx post-OHT	AHSCT1	CR	≥ 2
2	Only Rx pre-OHT	Mel-Pred	IFE positive	1
12	Only Rx post-OHT	AHSCT2	PR	≥ 2
3	Only Rx post-OHT	AHSCT1	CR	1
14	Only Rx post-OHT	AHSCT2	IFE positive	1
16	Only Rx post-OHT	AHSCT1	VGPR	≥ 2
7	Rx pre- and post-OHT	VBMCP	IFE positive	≥ 2
18	Only Rx post-OHT	AHSCT1	VGPR	1
5	Only Rx post-OHT	Mel-Pred	NA	1
10	No treatment	None	NA	0
19	Only Rx post-OHT	AHSCT2	PR	1
4	Rx pre- and post-OHT	Mel-Pred	IFE positive	≥ 2
21	Only Rx post-OHT	AHSCT2	No response	≥ 2
13	Only Rx post-OHT	AHSCT1	IFE positive	1
11	Only Rx post-OHT	AHSCT2	IFE positive	1
15	No treatment	None	NA	0
20	Only Rx post-OHT	Dex	CR	1
6	No treatment	None	NA	0

¹Melphalan conditioning 200 mg/m²;

²Melphalan conditioning 140 mg/m² in all but OHT #12 who got 150 mg/m²;

³Patient had AHSCT as second line and received Melphalan conditioning 200 mg/m². Amyloid directed therapy: AHSCT: Autologous hematopoietic stem cell transplant; Mel: Oral melphalan; Pred: Prednisone; Bortez: Bortezomib; Dex: Dexamethasone; VBMCP: Vincristine, BCNU, melphalan, cytoxan, prednisone; NA: Not available; CR: Complete hematologic response; PR: Partial response; VGPR: Very good partial response; IFE: Immunofixation.

Table 4 Orthotopic heart transplantation in patients with amyloidosis

Ref.	n	AHSCT	Outcomes
Current series	23	13	1-yr OS 77%
			5-yr OS 43%
MGH[10]	18	14	5-yr OS 60%
United Kingdom 2004[19]	171	3	1-yr 59%
			5-yr approximately 37%
United Kingdom 2010[17]	141	8	1-yr OS 86%
			5-yr OS 45%
Spanish registry[28]	13	3	1-yr OS 43%
			5-yr OS 36%
German group[29]	12	5	1-yr OS 83%
			3-yr OS 83%
ISHLT Registry[8,30]	102	None	1-yr 88%
			4-yr 38%
Maurer[16]	10	8	1-yr 90%
Stanford[20]	9	5	1-yr 100%
French registry[31]	8	3	1-yr 89%

¹Unclear how much overlap between these two groups. Intervals for Dubrey series was 1982-2002 and for Sattianayagam series, interval was 1984-2004, but there was no reference of which patients had been previously reported;

²At least 8 were AL; unclear what other 2 were. ISHT: International Society for Heart Transplant; OS: Overall survival; AHSCT: Autologous hematopoietic stem cell transplantation.