Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

Table 1

Summary of studies evaluating use of haploidentical transplantation, along with reported outcomes.

Study	Indications for transplant	HSC manipulation	Study group		Conditioning	HSC source	Engraft rate (%)	aGVHD II–IV (%)	cGVHD (%)	Relapse (%)	PFS/DFS/EFS (%)	OS (%)
[65]	2174 AML	Unmanipulated (T cell replete)	Haplo	192	104 myeloablative CNI, MMF, and PTCy	85 BM, 19 PB	90	16	30	44	24	3 yr OS 45
					88 RIC CNI, MMF, and PTCy	77 BM, 11 PB	93	19	34	58	18	3 yr OS 46
			MUD (8/8)	1982	1245 myeloablative CNI + MMF/MTX	231 BM, 1014 PB	97	33	53	39	12	3 yr OS 50
					737 RIC CNI + MMF/MTX	80 BM, 657 PB	96	28	52	42	10	3 yr OS 44
[66]	227 AML/MDS	Unmanipulated (T cell replete)	MRD	87	Fludarabine, melphalan, tacrolimus, and mini-MTX	2 BM, 23 PB	99	31	43	28	36	56
			MUD	108	Fludarabine, melphalan, tacrolimus, mini-MTX, and ATG	10 BM, 16 PB	96	29	30	23	27
			Haplo	32	Fludarabine, melphalan, thiotepa, PTCy, tacrolimus, and MMF	18 BM, 1 PB	97	29	19	33	30	66
[67]	450 AML	Unmanipulated (T cell replete)	Haplo	231	Cytarabine, busulfan, Cy, Me-CCNU, and ATG; CsA, MMF, and MTX	Combined	100	36	42	15	74	79
			MRD (Sib)	219	Hydroxycarbamide, cytarabine, busulfan, Cy, Me-CCNU, and ATG; CsA, MMF, and MTX	14 BM, 81 PB, 124 combined	100	13	15	15	78	82
[68]	82 ALL	Unmanipulated (T cell replete)	MRD/MUD	35	TBI, Cy, MMF, CsA, and MTX imatinib	Not specified		26	26	45	46	63
			Haplo	47	Ara-C, Cy, ATG, MMF, CsA, and MTX imatinib			51	49	19	60	64
[69]	918 AML	Unmanipulated (T cell replete)	CB	558	Various (276 MAC, 280 RIC)	558 cord	84	31	24		38
			Haplo	360	Various (219 MAC, 141 RIC)	171 BM, 175 PB, 14 combined	91	27	29	(NS)	32
	528 ALL	Unmanipulated (T cell replete)	CB	370	Various (261 MAC, 108 RIC)	370 cord	80	31	25		28
			Haplo	158	Various (111 MAC, 43 RIC)	65 BM, 78 PB, 15 combined	94	33	31		34
[70]	7874 AML, 2805 ALL	T cell depleted	MRD	297	Various	⁢1585 BM, 8174 PB, 56 combined		24	30	31	48
		Unmanipulated (T cell replete)		9518	Various				37	32	52	⁢
		T cell depleted	Haplo	268	Various	⁢ 284 BM, 544 PB, 36 combined		25	17	25	21
		Unmanipulated (T cell replete)		596	Various				27	40	30
[71]	90 HL	Unmanipulated (T cell replete)	MRD	38	Various: TBI fludarabine, MMF, or CsA + tacrolimus	38 PBSC	95	50	50	56	23	53
			MUD/mmUD	24		24 PBSC	99	50	63	63	29	58
			Haplo	28	Nonmyeloablative: Cy, fludarabine, TBI, PTCy, tacrolimus, and MMF	28 BM	100	43	35	40	51	58
[72]	718 NHL, 199 HL	Unmanipulated (T cell replete)	MUD	241	Various (fludarabine + busulfan/Cy/melphalan TBI) + ATG	26 NM, 279 PBSC	97	49	33	36	38	50
				491	Various (fludarabine + busulfan/Cy/melphalan TBI) without ATG	31 BM, 460 PBSC	97	40	51	28	49	62
			Haplo	185	RIC (fludarabine, Cy, TBI, and PTCy)	172 BM, 13 PBSC	94	27	13	36	47	60
[55]	26 HL	Unmanipulated (T cell replete)	Haplo	26	(RIC) Cy, fludarabine, low dose TBI, PTCy, tacrolimus/CsA, and MMF	26 BM	96	24	9	31	63	77
[56]	91 AML, 44 NHL, 41 ALL, 26 CML/MPD, 22 MDS, 17 HL, 15 CLL, 13 MM, and 2 others	Unmanipulated (T cell replete)	MRD	117	Various	7 BM, 108 PB, 2 combined	98	8	54	34	53	76
			MUD	101	Various	6 BM, 92 PB	98	11	54	34	52	67
			Haplo	53	35 nonmyeloablative: fludarabine, TBI, Cy, PTCy, tacrolimus, and MMF. 18 myeloablative: fludarabine, busulfan, Cy, PTCy, tacrolimus, and MMF	32 BM, 21 PB	98	11	38	33	60	64
[73]	170 AML, 62 ALL, 70 NHL, 53 MDS, 29 HL, 29 CML, 26 CLL, 21 MPD, and 15 MM	Unmanipulated (T cell replete)	MRD	181	Various. Tacrolimus and MTX for GVHD prophylaxis	2 BM, 179 PBSC	98	21	58	30	56	72
			MUD	178	Various. Tacrolimus and MTX for GVHD prophylaxis	32 BM, 146 PBSC	98	48	62	34	50	59
			Haplo	116	Nonmyeloablative (fludarabine, TBI, Cy, and PTCy) or myeloablative (fludarabine, busulfan, Cy, PTCy or fludarabine, TBI, and PTCy)	64 BM, 52 PBSC	97	41	38	29	54	57
[74]	42 AML, 30 NHL, 22 MDS, 17 MM, 10 ALL, 10 CLL, 4 MPD, 3 HL, and 3 CML	Unmanipulated (T cell replete)	MRD	47	RIC (fludarabine, busulfan, ATG, CsA, and MMF)	47 PB	100	21	35	25	64	78
			MUD/MMUD	63	RIC (fludarabine, busulfan, ATG, CsA, and MMF)	3 BM, 60 PB	100	44	24	31	38	51
			Haplo	31	Initially nonmyeloablative (Cy, fludarabine, and TBI) increased if necessary to RIC (Cy/thiotepa, fludarabine, and busulfan) + PTCy, CsA, and MMF	4 BM, 27 PB	97	23	13	23	67	70
[75]	29 HL, 24 NHL, 4 CLL, 4 AML/MDS, 4 MM, and 2 ALL	Unmanipulated (T cell replete)	Haplo BM	46	(RIC) Cy, fludarabine, low dose TBI, PTCy, tacrolimus/CsA, and MMF	46 BM	87	25	13		62	68
			Haplo PB	23		23 PB	95	33	13
[76]	38 AML, 20 ALL, 11 NHL, 7 MDS/MPD, and 1 SAA	Fixed CD3 DLI, positive CD34 selection	MRD	27	TBI, Cy, tacrolimus, and MMF	27 DLI	100	8	12	27	70	71
			Haplo	50	TBI, Cy, tacrolimus, and MMF	50 DLI	96	40	19	21	68	70
[77]	16 AML, 4 ALL, 3 NHL, 2 MDS, 1 SAA, and 1 other	Fixed CD3 DLI w/OKT3	Haplo	27	TBI, Cy, tacrolimus, and MMF	27 PB	85	59	16	32		48
[78]	15 AML, 10 ALL, 2 NHL, and 1 MDS	Fixed CD3 DLI, positive CD34 selection	Haplo	28	TBI, Cy, tacrolimus, and MMF	28 PB	100	39	22		2 yr DFS 74	2 yr OS 77
[79]	15 AML, 2 ALL, 2 MDS, and 1 CML	Unmanipulated (T cell replete)	Haplo 1 PTCy	9	Fludarabine, cytarabine, ATG, busulfan/melphalan, and PTCy	9 PB	95	56	10		35	44
			Haplo 2 PTCy	11	Fludarabine, cytarabine, ATG, busulfan/melphalan, and PTCy 2	11 PB		64				64
[80]	25 AML, 12 ALL, 5 HL/NHL, 4 MF, 3 CML, and 1 MPD	Unmanipulated (T cell replete)	Haplo	50	Thiotepa, busulfan, and fludarabine; PTCy, CsA, and MMF; or TBI, fludarabine, PTCy, CsA, and MMF	50 BM	90	12	26	26	51	62
[81]	232 AML/ALL, 59 HL/NHL, 74 MPD, 81 MDS, and 13 others	Unmanipulated (T cell replete)	MRD (Sib)	176	Various myeloablative or RIC. GvHD prophylaxis CsA, MTX	156 BM, 20 PB		31	29	40	32	45
			MUD	43	Various myeloablative or RIC. GvHD prophylaxis CsA, MTX, and ATG	26 BM, 17 PB		21	22	23	36	43
			MMUD	43	Various myeloablative or RIC. GvHD prophylaxis CsA, MTX, and ATG	28 BM, 15 PB		42	19	30	34	40
			CB	105	Various myeloablative or RIC. GvHD prophylaxis CsA, MMF, and ATG	105 cord		19	23	30	33	34
			Haplo	92	Thiotepa, busulfan, and fludarabine; PTCy, CsA, and MMF; or TBI, fludarabine, PTCy, CsA, and MMF	92 BM		14	15	35	43	52
[54]	16 AML, 12 NHL, 9 HL, 5 MDS, 4 SAA, 4 CLL, 3 CML, and 2 ALL	Unmanipulated (T cell replete)	Haplo	55	RIC (fludarabine, Cy, TBI, PTCy, tacrolimus, and MMF)	55 PB	96	61	18	28	51	48
[82]	12 AML, 3 CML, 2 ALL, 2 NHL, and 1 HL	Unmanipulated (T cell replete)	Haplo	20	Fludarabine, busulfan Cy and PTCy, tacrolimus, and MMF	20 PB	100	30	35	40	50	69

, no statistical comparison available, and data not reported.
AML: acute myeloid leukaemia, ALL: acute lymphoblastic leukaemia, HL: Hodgkin’s lymphoma, NHL: non-Hodgkin’s lymphoma, CLL: chronic lymphocytic leukaemia, CML: chronic myeloid leukaemia, MM: multiple myeloma, SAA: severe aplastic anaemia, MDS: myelodysplastic syndrome, MPD: myeloproliferative disorder, SCD: sickle cell disease, Haplo: haploidentical transplant, MUD: matched unrelated donor transplant, MRD: matched related donor transplant, Sib: matched sibling donor transplant, MMUD: mismatched unrelated donor transplant, RIC: reduced intensity conditioning, MAC: myeloablative conditioning, CNI: calcineurin inhibitor, MMF: mycophenolate mofetil, PTCy: posttransplant cyclophosphamide, Cy: cyclophosphamide, MTX: methotrexate, Me-CCNU: methyl chloride hexamethylene urea nitrate, ATG: antithymocyte globulin, CsA: ciclosporin A, TBI: total body irradiation, OKT3: muromonab CD3, BM: bone marrow, PB: peripheral blood stem cell, CB: cord blood transplant, DLI: donor leucocyte infusion, aGVHD: acute graft-versus-host disease, cGVHD: chronic graft-versus-host disease, TRM: transplant-related mortality, PFS: progression-free survival, DFS: disease-free survival, EFS: event-free survival, and OS: overall survival.