Allogeneic hematopoietic cell transplantation using fludarabine plus myeloablative busulfan and melphalan confers promising survival in high-risk hematopoietic neoplasms: a single-center retrospective analysis

Figures & data

Table 1 Patient and transplant characteristics.

Characteristics	Total (N = 39)	MEL140 group** (N = 26)	MEL80 group (N = 13)	P
Age
Median (range), yr	50 (17–68)	45.5 (17–60)	58 (33–68)	<0.001
Distribution, no (%)				0.041
<50 yr	19 (49)	16 (62)	3 (23)
50 yr or older	20 (51)	10 (38)	10 (77)
Sex, no. (%)				0.725
Female	13 (33)	8 (31)	5 (38)
Male	26 (67)	18 (69)	8 (62)
Disease, no. (%)				0.072
Myeloid neoplasms	23 (59)	14 (54)	9 (69)
AML	14 (36)	11 (42)	3 (23)
MDS	2 (5)	1 (4)	1 (8)
MPN and MDS/MPN	5 (13)	2 (8)	3 (23)
Therapy-related myeloid neoplasms	2 (5)	0 (0)	2 (15)
Lymphoid neoplasms	16 (41)	12 (46)	4 (31)
ALL	10 (26)	9 (35)	1 (8)
Mature B cell neoplasms	2 (5)	1 (4)	1 (8)
Mature T/NK cell neoplasms	4 (10)	2 (8)	2 (15)
Disease risk, no. (%)				1.00
Standard	23 (59)	15 (58)	8 (62)
High	16 (41)	11 (42)	5 (38)
Graft source, no. (%)				0.916
Related bone marrow	2 (5)	2 (8)	0 (0)
Related peripheral blood	10 (26)	7 (27)	3 (23)
Unrelated bone marrow	9 (23)	6 (23)	3 (23)
Unrelated peripheral blood	1 (3)	1 (4)	0 (0)
Unrelated cord blood	17 (44)	10 (38)	7 (54)
HLA mismatch*, no. (%)				0.064
0 antigen	25 (64)	17 (65)	8 (62)
1 antigen	3 (8)	0 (0)	3 (23)
2 antigens	10 (26)	8 (31)	2 (15)
3 antigens	1 (3)	1 (4)	0 (0)
GVHD prophylaxis, no. (%)				1.00
Cyclosporin-based	28 (72)	19 (73)	9 (69)
Tacrolimus-based	11 (28)	7 (27)	4 (31)

AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; MDS/MPN, myelodysplastic/myeloproliferative neoplasms; ALL, acute lymphoblastic leukemia; MEL140, melphalan 140 mg/m²; MEL80, melphalan 80 mg/m².

*Defined as the higher number of mismatched HLA-A, -B, and -DR antigens in either graft-versus-host or host-versus-graft directions. All of 2 or 3 antigens-mismatched cases were cord blood transplants.

**Including one unrelated peripheral blood transplant using anti-thymocyte globulin and three cord blood transplants using 2 Gy of total-body irradiation in addition to FLU-BU-MEL140 regimen.

Figure 1. Overall survival after allogeneic hematopoietic cell transplants using FBM regimen. (A) Survival rate for the entire cohort. (B) Survival rates stratified by the disease risk groups.

Table 2 Univariable and multivariate analyses for pretransplant variables potentially associated overall mortality.

Variables	Univariable analysis			Multivariate analysis
	HR	95% CI	P	HR	95% CI	P
Age
<50 yr	1.00	Reference		1.00	Reference
50 yr or older	9.15	1.98–42.2	0.005	6.60	1.31–33.2	0.022
Sex
Female	1.00	Reference		–	–
Male	1.33	0.41–4.33	0.633	–	–
Disease
Myeloid neoplasms	1.00	Reference		–	–
Lymphoid neoplasms	0.63	0.19–2.05	0.441	–	–
Disease status
Standard-risk	1.00	Reference		1.00	Reference
High-risk	3.13	1.01–9.65	0.046	2.26	0.72–7.09	0.163
Graft source
Bone marrow	1.00	Reference
Peripheral blood	1.23	0.28–5.53	0.781	–	–
Cord blood	1.13	0.57–2.28	0.722	–	–
Conditioning
MEL80-based	1.00	Reference		1.00	Reference
MEL140-based	0.33	0.11–1.01	0.052	0.66	0.21–2.08	0.478
GVHD prophylaxis
Cyclosporin-based	1.00	Reference		–	–
Tacrolimus-based	0.50	0.11–2.27	0.37	–	–

Figure 2. Cumulative incidence of neutrophil engraftment after FBM regimen. (A) Incidence rate of neutrophil engraftment by types of graft source. (B) Incidence rate of neutrophil engraftment separated by the MEL140 and MEL80 groups.

Figure 3. Cumulative incidence of acute and chronic GVHD according to types of graft source. (A) Incidence of grade II to IV acute GVHD within 100 days after transplantation. (B) Incidence of grade III or IV acute GVHD within 100 days after transplantation. (C) Incidence of chronic GVHD of any severity by NIH criteria.

Table 3 Incidence of grade 3–4 regimen toxicities, VOD/SOS and TMA within 28 days after transplant.

Regimen-related toxicity, n(%)	Total (N = 39)	MEL140 group (N = 26)	MEL80 group (N = 13)
Neurologic toxicity, no (%)
Cerebral bleeding	1 (2)	0 (0)	1 (7)
Cardiac toxicity, no (%)	0 (0)	0 (0)	0 (0)
Pulmonary toxicity, no(%)	1 (2)	1 (3)	0 (0)
Gastrointestial toxicity, no (%)
Oral mucositis	20 (51)	13 (50)	7 (53)
Diarrhea	19 (48)	14 (53)	5 (38)
Gastrointestinal bleeding	7 (17)	4 (15)	3 (23)
Hepatic toxicity, no (%)
Transaminitis	2 (5)	1 (3)	1 (7)
Hyperbilirubinemia*	3 (7)	1 (3)	2 (15)
SOS/VOD	3 (7)	1 (3)	2 (15)
Renal toxicity, no (%)
Creatinine elevation	2 (5)	0 (0)	2 (15)
TMA, no (%)	2 (5)	1 (3)	1 (7)

SOS/VOD, sinusoidal obstructive syndrome/veno-occulsive disease; TMA, transplant-associated thrombomicroangiopathy. *Hyperbilirubinemia not associated with either SOS/VOD or TMA.

Figure 5. Cumulative relapse incidence and non-relapse mortality in the MEL140 and MEL80 groups. (A) Relapse incidence (B) Non-relapse mortality