J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Original Article

Volume 12, Number 6, December 2023, pages 255-267

Haploidentical and Matched Sibling Transplantation for Acute Myeloid Leukemia: A Hospital-Based Study

Figure 1. Comparison of overall survival of allogeneic hematopoietic stem cell transplantation, 2013 - 2019. There is no statistically significant difference between groups (P = 0.142). HRD: haploidentical related donor; MSD: HLA-matched sibling donor.

Figure 2. Overall and comparison of relapse-free survival in allogeneic hematopoietic stem cell transplantation, 2013 - 2019. (a) Overall of relapse-free survival. (b) Comparison of relapse-free survival. There is no statistically significant difference between groups (P = 0.188). HRD: haploidentical related donor; MSD: HLA-matched sibling donor.

Figure 3. Overall and comparison of non-relapse mortality after allogeneic hematopoietic stem cell transplantation, 2013 - 2019. There is no statistically significant difference between groups (P = 0.190). (a) Overall of non-relapse mortality. (b) Comparison of non-relapse mortality. HRD: haploidentical related donor; MSD: HLA-matched sibling donor.

Figure 4. Comparison of relapse after allogeneic hematopoietic stem cell transplantation, 2013 - 2019. There is no statistically significant difference between groups (P = 0.537). HRD: haploidentical related donor; MSD: HLA-matched sibling donor.

**Table 1.** Patients and Hematopoietic Stem Cell Transplantation Characteristics (n = 50)
Characteristics	Total (n = 50)	Type of hematopoietic stem cell transplantation	P-value
FAB: French-American-British cooperative team; HRD: haploidentical related donor; IQR: interquartile range; MSD: HLA-matched sibling donor.
Median patient/recipient age (IQR), years	38 (24 - 47)	38 (23 - 46)	37 (24 - 50)	0.824
Median donor age (IQR), years	31 (22 - 41)	40 (25 - 43)	29 (20 - 38)	0.075
Male sex, n (%)	22 (44)	5(28)	17 (53)	0.083
FAB categories, n (%)
M0 = 0	11 (22)	4 (22)	7 (22)	0.732
M1 = 1	9 (18)	5 (28)	4 (13)
M2 = 2	8 (16)	3 (17)	5 (16)
M4	3 (6)	-	3 (9)
M5	6 (12)	1 (6)	5 (16)
M5b	3 (6)	1 (6)	2 (6)
NOS	10 (20)	4 (22)	6 (19)
Pre-transplantation disease status, n (%)
First complete remission	31 (62)	8 (44)	23 (72)	0.227
Second complete remission	10 (20)	5 (28)	5 (16)
Third or beyond complete remission	3 (6)	2 (11)	1 (3)
Active disease	6 (12)	3 (17)	3 (9)
Median time of follow-up (IQR), months	9 (4 - 22)	10 (6 - 23)	8 (3 - 23)	0.293
Neutrophil engraftment, n (%)	47 (94)	18 (100)	29 (90)	0.180
Median time of neutrophil engraftment (IQR), days	17 (13 - 19)	14 (12 - 18)	18 (15 - 19)	0.022
Platelets engraftment, n (%)	47 (94)	18 (100)	29 (90)	0.180
Median time of platelet engraftment (IQR), days	18 (14 - 24)	14 (12 - 19)	22 (16 - 25)	0.007

Table 1. Patients and Hematopoietic Stem Cell Transplantation Characteristics (n = 50)

Characteristics

Total (n = 50)

Type of hematopoietic stem cell transplantation

P-value

MSD (n = 18)

HRD (n = 32)

FAB: French-American-British cooperative team; HRD: haploidentical related donor; IQR: interquartile range; MSD: HLA-matched sibling donor.

Median patient/recipient age (IQR), years

38 (24 - 47)

38 (23 - 46)

37 (24 - 50)

0.824

Median donor age (IQR), years

31 (22 - 41)

40 (25 - 43)

29 (20 - 38)

0.075

Male sex, n (%)

22 (44)

5(28)

17 (53)

0.083

FAB categories, n (%)

M0 = 0

11 (22)

4 (22)

7 (22)

0.732

M1 = 1

9 (18)

5 (28)

4 (13)

M2 = 2

8 (16)

3 (17)

5 (16)

3 (6)

3 (9)

6 (12)

1 (6)

5 (16)

M5b

3 (6)

1 (6)

2 (6)

NOS

10 (20)

4 (22)

6 (19)

Pre-transplantation disease status, n (%)

First complete remission

31 (62)

8 (44)

23 (72)

0.227

Second complete remission

10 (20)

5 (28)

5 (16)

Third or beyond complete remission

3 (6)

2 (11)

1 (3)

Active disease

6 (12)

3 (17)

3 (9)

Median time of follow-up (IQR), months

9 (4 - 22)

10 (6 - 23)

8 (3 - 23)

0.293

Neutrophil engraftment, n (%)

47 (94)

18 (100)

29 (90)

0.180

Median time of neutrophil engraftment (IQR), days

17 (13 - 19)

14 (12 - 18)

18 (15 - 19)

0.022

Platelets engraftment, n (%)

47 (94)

18 (100)

29 (90)

0.180

Median time of platelet engraftment (IQR), days

18 (14 - 24)

14 (12 - 19)

22 (16 - 25)

0.007

**Table 2.** Mortality-Related Transplant Factors (n = 50)
Variable	Total (n = 50)	MSD (n = 18)	HRD (n = 32)	P-value
^an = 32. ^bn = 12. ^cn = 26. aGvHD: acute graft-versus-host disease; BUFLU TBI-400: fludarabine, busulfan plus 400 cGy fractionated total body irradiation; cGvHD: chronic graft-versus-host disease; Cy TBI-1320: cyclophosphamide plus 1,320 cGy fractionated total body irradiation; EBMT: The European Group for Blood and Marrow Transplantation; HRD: haploidentical related donor; IQR: interquartile range; MSD: HLA-matched sibling donor.
EBMT risk score
Low risk	24 (48)	8 (44)	16 (50)	0.928
Intermediate risk	14 (28)	5 (28)	9 (28)
High risk	12 (24)	5 (28)	7 (22)
Conditioning regimen, n (%)
BUFLU TBI-400	30 (63)	9 (56)	21 (66)	0.527
Cy TBI-1320	18 (37)	7 (44)	11 (34)
Median number of infused CD34⁺ (IQR), × 10⁶	10.25 (7.85 - 13.58)	11.04 (6.97 - 13.41)^b	9.92 (7.85 - 13.66)^c	0.224
aGvHD, n (%)^a
II-IV	14 (44)	4 (44)	10 (43)	1
III-IV	3 (9)	1 (11)	2 (9)	1
cGvHD, n (%)	18 (44)	8 (50)	10 (40)
Mild	13 (72)	5 (63)	8 (80)
Moderate	4 (22)	2 (25)	2 (20)	0.765
Severe	1 (6)	1 (12)	-
Cytomegalovirus viremia, n (%)	33 (66)	10 (56)	23 (72)	0.242

Table 2. Mortality-Related Transplant Factors (n = 50)

Variable

Total (n = 50)

MSD (n = 18)

HRD (n = 32)

P-value

^an = 32. ^bn = 12. ^cn = 26. aGvHD: acute graft-versus-host disease; BUFLU TBI-400: fludarabine, busulfan plus 400 cGy fractionated total body irradiation; cGvHD: chronic graft-versus-host disease; Cy TBI-1320: cyclophosphamide plus 1,320 cGy fractionated total body irradiation; EBMT: The European Group for Blood and Marrow Transplantation; HRD: haploidentical related donor; IQR: interquartile range; MSD: HLA-matched sibling donor.

EBMT risk score

Low risk

24 (48)

8 (44)

16 (50)

0.928

Intermediate risk

14 (28)

5 (28)

9 (28)

High risk

12 (24)

5 (28)

7 (22)

Conditioning regimen, n (%)

BUFLU TBI-400

30 (63)

9 (56)

21 (66)

0.527

Cy TBI-1320

18 (37)

7 (44)

11 (34)

Median number of infused CD34⁺ (IQR), × 10⁶

10.25 (7.85 - 13.58)

11.04 (6.97 - 13.41)^b

9.92 (7.85 - 13.66)^c

0.224

aGvHD, n (%)^a

II-IV

14 (44)

4 (44)

10 (43)

III-IV

3 (9)

1 (11)

2 (9)

cGvHD, n (%)

18 (44)

8 (50)

10 (40)

Mild

13 (72)

5 (63)

8 (80)

Moderate

4 (22)

2 (25)

2 (20)

0.765

Severe

1 (6)

1 (12)

Cytomegalovirus viremia, n (%)

33 (66)

10 (56)

23 (72)

0.242

**Table 3.** Literature Review of Haploidentical Related Donors and HLA-Matched Sibling Donors Transplants in Acute Myeloid Leukemia
Author/country	Design/period	Sample size	Engraft, n (%)	aGvHD	cGvHD	OS	RFS	Conditioning	NRM	Relapse
^aIt includes all cases of allogeneic PBSCT (not specific for acute myeloid leukemia). ^bThese results include both acute myeloid leukemia and acute lymphoblastic leukemia. aGvHD: acute graft-versus-host disease; ATG: anti-thymocyte globulin; BU: busulfan; cGvHD: chronic graft-versus-host disease; Cy: cyclophosphamide; FLU: fludarabine; HRD: haploidentical related donor; MAC: myeloablative conditioning; MRD: matched related donor; MSD: HLA-matched sibling donor; Neu: neutrophils; NMA: non-myeloablative; NRM: non-relapse mortality; OS: overall survival; Plt: platelets; RFS: relapse-free survival; RIC: reduced-intensity conditioning; TBI: total body irradiation.
Baena et al Colombia	Retrospective 2013 - 2019	MSD: 18 HRD: 32	Neu: 94% median 17 days Plt: 94% median 18 days	MSD (II-IV): 44% HRD (II-IV): 43%	MSD: 50% HRD: 40%	MSD: 62% 5 years HRD: 43% 5 years	MSD: 77% 5 years HRD: 57% 5 years	MAC with TBI: 100%	MSD: 6% day-100 HRD: 20% day-100	MSD: 18% 5 years HRD: 25% 5 years
Abello et al, 2008 [20] Colombia	Retrospective 1993 - 2007	46	-	-	-	53.2%^a	50.9%^a	MAC	-	-
Leon Rodriguez et al, 2017 [21] Mexico	Retrospective 1998 - 2017	19 (15%)	Neu: median 20 days Plt: median 16 days	21%^a	33%^a	48% 5 years	65% 10 years^a	MAC: 75% NMA: 25%	36%^a	58%^b
Trucco et al, 2017 [22] Argentina	Retrospective 2012 - 2016	MRD: 89 (36%) HRD: 83 (33%)	MRD: 35% ≥ 15 days HRD: 85% ≥ 15 days	MRD (II-IV): 27% HRD (II-IV): 33%	MRD: 22% HRD: 25%	MRD: 51% 3 years HRD: 34% 3 years	MRD: 42% 3 years HRD: 31% 3 years	MAC: 81%	MRD: 15% 3 years HRD: 29% 3 years	MRD: 44% 3 years HRD: 40% 3 years
Versluis et al, 2017 [23] Europe	Retrospective 2000 - 2014	MRD: 3,511 HRD: 193	MRD: 16 days HRD: 18 days	MRD (II-IV): 22% HRD (II-IV): 25%	MRD: 38±1% 2 years HRD: 37±4% 2 years	MRD: 59±1% 2 years HRD: 57±4% 2 years	MRD: 53±1% 2 years HRD: 52±4% 2 years	MRD: MAC 56% HRD: MAC 54%	MRD: 15±1% 2 years HRD: 26±3% 2 years	MRD: 30% 2 years HRD: 22±3% 2 years
Ostgard et al, 2018 [24] Denmark	Cohort 2000 - 2014	HRD: 196 MRD: 91 (46.4%)	-	-	-	Median 1,173 days	Median 1,068 days	MAC Cy TBI 90% BU-Cy 9% FLU-Treosulfan 1%	-	24%
Salvatore et al, 2018 [25] Europe	Retrospective 2007 - 2015	HRD: 185 MRD: 2,469		HRD (II-IV): 36% MRD (II-IV): 24%	HRD: 39% MRD: 33%	HRD: 67% MRD: 66%	-	MAC: HRD 50%, MRD 53% RIC: HRD 50%, MSD 47%	HRD: 18% 2 years MRD: 10% 2 years	HRD: 21% MRD: 36%
Liu et al, 2019 [26] China	Retrospective 2008 - 2015	MSD: 43 HRD: 127	Neu: 100% median 14.9 days Plt: 94.1% median 20.7 days	General (II-IV/III-IV): 40%/12.9% MRD (II-IV/III-IV): 27.9%/7% HRD (II-IV/III-IV): 44.1%/15%	-	General: 63.9% 3 years MRD: 63.0% HRD: 64.1%	General: 59.7% MRD: 51.8% HRD: 62.7%	HRD: cytarabine, BU, Cy, simustine, thymoglobulin MRD: hydroxyurea, cytarabine, BU, Cy, simustine	-	-
Rashidi et al, 2019 [27] USA	Retrospective 2008 - 2015	MRD: 869 HRD: 336	MRD: Neu 99% 1 month Plt 97% 100 days HRD: Neu: 92% 1 month Plt 89% 100 days	MRD (II-IV): 30% 6 months HRD (II-IV): 32% 6 months	MRD: 56% 3 years HRD: 26% 3 years	MRD: 55% 3 years HRD: 48% 3 years	MRD: 3 years 48%, HRD: 3 years 43%	MRD: MAC without TBI 45%, MAC with TBI 24% HRD: RIC/NMA 65%, MAC without TBI 25%	MRD: 14% 3 years HRD: 19% 3 years	MRD: 38% 3 years HRD: 38% 3 years
Figueroa et al, 2020 [28] Colombia	Descriptive cohort 2015 - 2018	66	-	MRD (III-IV): 23.7% HRD (III-IV): 12.8%^b	-	MRD: 72% 2 years HRD: 42% 2 years^b	-	MAC	-	MRD: 25% HRD: 22%^b
Yanada et al, 2020 [29] Japan	Retrospective 1992 - 2016	5,638	Neu: 14 days Plt: 21 days	35% 100 days	39% 2 years	41% 5 years	-	MAC: 71% RIC: 29%	26% 5 years	36% 5 years
Mehta et al, 2022 [30] USA	Retrospective 2015 - 2020	HRD: 661 MRD: 140	HRD: Neu 19 days, Plt 27 days MRD: 15 days, Plt 22 days	HRD (II-IV): 44% 180 days MRD (II-IV): 44% 180 days	HRD: 15% MRD: 16%	HRD: 50% MRD: 71%	-	MAC: HRD 24%, MRD 74% RIC: HRD 76%, MRD 26%	HRD: 32% MRD: 11%	HRD: 25% MRD: 30%
Rieger et al, 2023 [31] Switzerland	Retrospective 2015 - 2020	MSD: 68 HRD: 40	HRD: Neu median 16 days, Plt 26.5 days MRD: Neu median 12 days, Plt 15 days	MRD (II-IV): 14.7% HRD (II-IV): 27.5%	-	HRD: 50% 2 years MRD: 77% 2 years	-	MAC BU-Cy-ATG: MRD 30.9%, HRD 0% BU-Cy: MRD 2.9%, HRD: 22.5% FLU-Cy-sTBI: MRD 0%, HRD: 12.5% Other: MRD 7.4%, HRD 0% RIC regimens FLU-BU-ATG: MRD 48.5%, HRD 0% FLU-BU: MRD 2.9%, HRD 65% Other: MRD 7.4%, HRD 0%	HRD: 18% 2 years MRD: 2.9% 2 years	-

Table 3. Literature Review of Haploidentical Related Donors and HLA-Matched Sibling Donors Transplants in Acute Myeloid Leukemia

Author/country

Design/period

Sample size

Engraft, n (%)

aGvHD

cGvHD

RFS

Conditioning

NRM

Relapse

^aIt includes all cases of allogeneic PBSCT (not specific for acute myeloid leukemia). ^bThese results include both acute myeloid leukemia and acute lymphoblastic leukemia. aGvHD: acute graft-versus-host disease; ATG: anti-thymocyte globulin; BU: busulfan; cGvHD: chronic graft-versus-host disease; Cy: cyclophosphamide; FLU: fludarabine; HRD: haploidentical related donor; MAC: myeloablative conditioning; MRD: matched related donor; MSD: HLA-matched sibling donor; Neu: neutrophils; NMA: non-myeloablative; NRM: non-relapse mortality; OS: overall survival; Plt: platelets; RFS: relapse-free survival; RIC: reduced-intensity conditioning; TBI: total body irradiation.

Baena et al
Colombia

Retrospective
2013 - 2019

MSD: 18
HRD: 32

Neu: 94% median 17 days
Plt: 94% median 18 days

MSD (II-IV): 44%
HRD (II-IV): 43%

MSD: 50%
HRD: 40%

MSD: 62% 5 years
HRD: 43% 5 years

MSD: 77% 5 years
HRD: 57% 5 years

MAC with TBI: 100%

MSD: 6% day-100
HRD: 20% day-100

MSD: 18% 5 years
HRD: 25% 5 years

Abello et al, 2008 [20]
Colombia

Retrospective
1993 - 2007

53.2%^a

50.9%^a

MAC

Leon Rodriguez et al, 2017 [21]
Mexico

Retrospective
1998 - 2017

19 (15%)

Neu: median 20 days
Plt: median 16 days

21%^a

33%^a

48% 5 years

65% 10 years^a

MAC: 75%
NMA: 25%

36%^a

58%^b

Trucco et al, 2017 [22]
Argentina

Retrospective
2012 - 2016

MRD: 89 (36%)
HRD: 83 (33%)

MRD: 35% ≥ 15 days
HRD: 85% ≥ 15 days

MRD (II-IV): 27%
HRD (II-IV): 33%

MRD: 22%
HRD: 25%

MRD: 51% 3 years
HRD: 34% 3 years

MRD: 42% 3 years
HRD: 31% 3 years

MAC: 81%

MRD: 15% 3 years
HRD: 29% 3 years

MRD: 44% 3 years
HRD: 40% 3 years

Versluis et al, 2017 [23]
Europe

Retrospective
2000 - 2014

MRD: 3,511
HRD: 193

MRD: 16 days
HRD: 18 days

MRD (II-IV): 22%
HRD (II-IV): 25%

MRD: 38±1% 2 years
HRD: 37±4% 2 years

MRD: 59±1% 2 years
HRD: 57±4% 2 years

MRD: 53±1% 2 years
HRD: 52±4% 2 years

MRD: MAC 56%
HRD: MAC 54%

MRD: 15±1% 2 years
HRD: 26±3% 2 years

MRD: 30% 2 years
HRD: 22±3% 2 years

Ostgard et al, 2018 [24]
Denmark

Cohort
2000 - 2014

HRD: 196
MRD: 91 (46.4%)

Median 1,173 days

Median 1,068 days

MAC
Cy TBI 90%
BU-Cy 9%
FLU-Treosulfan 1%

24%

Salvatore et al, 2018 [25]
Europe

Retrospective
2007 - 2015

HRD: 185
MRD: 2,469

HRD (II-IV): 36%
MRD (II-IV): 24%

HRD: 39%
MRD: 33%

HRD: 67%
MRD: 66%

MAC: HRD 50%, MRD 53%
RIC: HRD 50%, MSD 47%

HRD: 18% 2 years
MRD: 10% 2 years

HRD: 21%
MRD: 36%

Liu et al, 2019 [26]
China

Retrospective
2008 - 2015

MSD: 43
HRD: 127

Neu: 100% median 14.9 days
Plt: 94.1%
median 20.7 days

General (II-IV/III-IV): 40%/12.9%
MRD (II-IV/III-IV): 27.9%/7%
HRD (II-IV/III-IV): 44.1%/15%

General: 63.9% 3 years
MRD: 63.0%
HRD: 64.1%

General: 59.7%
MRD: 51.8%
HRD: 62.7%

HRD: cytarabine, BU, Cy, simustine, thymoglobulin
MRD: hydroxyurea, cytarabine, BU, Cy, simustine

Rashidi et al, 2019 [27]
USA

Retrospective
2008 - 2015

MRD: 869
HRD: 336

MRD: Neu 99% 1 month
Plt 97% 100 days
HRD: Neu: 92% 1 month
Plt 89% 100 days

MRD (II-IV): 30% 6 months
HRD (II-IV): 32% 6 months

MRD: 56% 3 years
HRD: 26% 3 years

MRD: 55% 3 years
HRD: 48% 3 years

MRD: 3 years 48%, HRD: 3 years 43%

MRD: MAC without TBI 45%, MAC with TBI 24%
HRD: RIC/NMA 65%, MAC without TBI 25%

MRD: 14% 3 years HRD: 19% 3 years

MRD: 38% 3 years
HRD: 38% 3 years

Figueroa et al, 2020 [28]
Colombia

Descriptive cohort
2015 - 2018

MRD (III-IV): 23.7%
HRD (III-IV): 12.8%^b

MRD: 72% 2 years
HRD: 42% 2 years^b

MAC

MRD: 25%
HRD: 22%^b

Yanada et al, 2020 [29]
Japan

Retrospective
1992 - 2016

5,638

Neu: 14 days
Plt: 21 days

35% 100 days

39% 2 years

41% 5 years

MAC: 71%
RIC: 29%

26% 5 years

36% 5 years

Mehta et al, 2022 [30]
USA

Retrospective
2015 - 2020

HRD: 661
MRD: 140

HRD: Neu 19 days, Plt 27 days
MRD: 15 days, Plt 22 days

HRD (II-IV): 44% 180 days
MRD (II-IV): 44% 180 days

HRD: 15%
MRD: 16%

HRD: 50%
MRD: 71%

MAC: HRD 24%, MRD 74%
RIC: HRD 76%, MRD 26%

HRD: 32%
MRD: 11%

HRD: 25%
MRD: 30%

Rieger et al, 2023 [31]
Switzerland

Retrospective
2015 - 2020

MSD: 68
HRD: 40

HRD: Neu median 16 days, Plt 26.5 days
MRD: Neu median 12 days, Plt 15 days

MRD (II-IV): 14.7%
HRD (II-IV): 27.5%

HRD: 50% 2 years
MRD: 77% 2 years

MAC
BU-Cy-ATG: MRD 30.9%, HRD 0%
BU-Cy: MRD 2.9%, HRD: 22.5%
FLU-Cy-sTBI: MRD 0%, HRD: 12.5%
Other: MRD 7.4%, HRD 0%
RIC regimens
FLU-BU-ATG: MRD 48.5%, HRD 0%
FLU-BU: MRD 2.9%, HRD 65%
Other: MRD 7.4%, HRD 0%

HRD: 18% 2 years
MRD: 2.9% 2 years