HLA-mismatched haploidentical transplantation using low-dose anti-thymocyte globulin (ATG: thymoglobulin)

Figures & data

Table 1. Patient characteristics.

Number	Age/Sex	Diagnosis	Disease status	Regimen	CMV/EBV VCA- IgG	Previous HSCT^a	Previous donor	CR duration after the 1st HSCT [days]	Duration between the 1st and 2nd HSCT [days]
1	45/F	AML	RL1	ivBu/Mel/ATG	+/+	+	MMRD	211	251
2	31/M	ALL	RL1	CY/TBI/ATG	+/unknown	−
3	34/M	AML	CR2	Flu/Mel/TBI/ATG	+/+	+	MUD	282	439
4	55/M	AML	RL1	ivBu/Mel/ATG	+/+	+	MMRD	828	1214
5	50/F	CMML	RL1	CY/TBI/ATG	−/+	+	MUD	393	520
6	23/F	Ph+ ALL^b	CR1	CY/TBI/ATG	−/+	−
7	19/F	Ph+ ALL^b	CR2	Flu/Mel/TBI/ATG	+/+	+	MRD	519	757
8	15/M	AML	RL1	CY/TBI/ATG	+/+	−
9	19/M	NHL	PIF	CY/TBI/ATG	+/+	−
10	24/F	AML	PIF	CY/TBI/ATG	+/+	−
11	39/M	LCS	RL1	Flu/Mel/TBI/ATG	−/+	+	CB	659	1495
12	64/M	PMF	Int-1^c	Flu/ivBu/TBI/ATG	+/+	−

^aNo patient had received autologous HSCT.

^bThese patients were not in molecular remission.

^cThe diagnosis of Int-1 was made according to the dynamic international prognostic scoring system.

Abbreviations: CMV, cytomegalovirus; EBV, Epstein–Barr virus; VCA, viral capsid antigen; HSCT, hematopoietic stem cell transplantation; CR, complete remission; AML, acute myelogenous leukemia; ALL, acute lymphoblastic leukemia; CMML, chronic myelomonocytic leukemia; Ph+, Philadelphia chromosome-positive; NHL, non-Hodgkin lymphoma; LCS, Langerhans cell sarcoma; PMF, primary myelofibrosis; RL, relapse; PIF, primary induction failure; PD, progression disease; Int-1, Intermediate-1; ivBu, intravenous busulfan; Mel, melphalan; ATG, anti-thymocyte globulin; CY, cyclophosphamide; TBI, total body irradiation; Flu, fludarabine; MMRD, human leukocyte antigen (HLA)-mismatched related donor; MUD, HLA-matched unrelated donor; MRD, HLA-matched related donor; CB, cord blood.

Table 2. Donor characteristics.

Number	Relationship	Age	Number of antigen MM in the GVH direction^a	Number of antigen MM in the HVG direction^a	Blood type MM	CMV/EBV VCA-IgG	Number of CD34+ cells in the graft [×10^6/kg]	Number of CD3+ cells in the graft [×10^8/kg]
1	Sister^b	42	3	2	−	+/+	3.3	3.2
2	Father	60	3	3	−	+/+	4.4	2.5
3	Brother	30	2	3	−	+/+	4.8	1.44
4	Brother^b	53	2	2	−	+/+	4.2	1.2
5	Son	23	2	2	−	+/+	3.2	2.6
6	Father	47	2	2	−	+/+	5.7	0.6
7	Brother	27	3	3	−	+/+	3.7	0.5
8	Father	52	2	3	−	+/+	3.0	1.2
9	Brother	22	2	2	−	+/+	3.6	1.5
10	Brother	29	3	3	−	+/+	3.3	1.5
11	Sister	43	3	3	−	+/+	3.1	1.6
12	Son	25	3	3	Major	+/+	3.1	1.2

^aNumber of antigen MM was counted in HLA-A; B, DR antigens.

^bThese donors also donated graft in the 1st allogeneic hematopoietic stem cell transplantation.

Abbreviations: MM; mismatch; GVH, graft-versus-host; HVG, host-versus-graft; CMV, cytomegalovirus; EBV, Epstein–Barr virus; VCA, viral capsid antigen.

Figure 1. Transplantation outcomes. Overall survival (A), progression-free survival (B), and the relapse/progression rate and non-relapse/progression mortality (C) from transplantation in all patients.

Table 3. Transplantation outcomes.

Number	Engraftment [days] (Use of G-CSF)	Plt > 20 × 10^9/l [days]	CR achievement [days]	Acute GVHD	Chronic GVHD	Relapse [days]	CMV infection/disease	EBV-LPD	Outcomes [days]	Cause of death
1	27 (−)	26	30	−	Extensive	233	+/−	−	Died 288	Relapse
2	17 (+)	28	31	2	Extensive^a	60	−/−	−	Died 231	Relapse
3	23 (−)	24	CR before HSCT	−	Limited	−	+/−	−	Alive 1711	NA
4	− (+)	−	−	–	NA	NA	−/−	−	Died 27	Sepsis
5	27 (−)	26	34	1	Limited	150	+/−	−	Died 328	Relapse
6	16 (+)	26	CR before HSCT	3	Extensive	−	−/−	+	Alive 1280	NA
7	15 (+)	25	CR before HSCT	−	−	321	−/−	−	Alive 1077	NA
8	15 (+)	−	38	−	NA	96	−/−	−	Died 122	Relapse
9	15 (+)	29	−	−	NA	NA	−/−	−	Died 72	Progression
10	73 (−)	80	39	1	−	−	+/−	−^b	Alive 157	NA
11	14 (+)	20	17	1	−	−	−/−	−^b	Alive 147	NA
12	51 (−)	−	31	1	−	−	+/−	−^b	Died 113	IPS

^aExtensive chronic GVHD developed after relapse and rapid tapering of immunosuppressive agents.

^bRituximab was administered for high EBV-DNA load.

Abbreviations: G-CSF, Granulocyte-colony stimulating factor; Plt, platelet; CR, complete remission; GVHD, graft-versus-host disease; CMV, cytomegalovirus; EBV-LPD, Epstein–Barr virus-related lymphoproliferative disorder; HSCT, hematopoietic stem cell transplantation; DNA, deoxyribonucleic acid; IPS, idiopathic pneumonia syndrome.

Figure 2. Immune reconstitution. Immune reconstitution was evaluated by the quantification of CD3+/CD4+ and CD3+/CD8+ cells by flowcytometry in nine of ten patients who achieved CR after allogeneic hematopoietic stem cell transplantation (HSCT). The geometric mean values were calculated using the cell counts at 1 month, 2 months, 3 months, 6 months, and 12 months after HSCT.