Double vs. single cord blood transplantation in adolescent and adult hematological malignancies with heavier body weight (≥50 kg)

Figures & data

Figure 1. Flow diagram of the study.

Table 1. Patients’ and transplant characteristics.

Characteristics	Double-unit CBT	Single-unit CBT	p
Total (n)	37	60
Age at transplantation (years): median (range)	24 (14–51)	23 (15–46)	0.31
Sex: male/female	29/8	40/20	0.32
Body weight (kg)	65 (50–90)	60 (50–100)	0.25
Underlying disease (n, %)			0.59
ALL	13 (35.1)	25 (41.7)
AML	10 (27.0)	15 (25.0)
CML-CP	6 (16.2)	4 (6.7)
CML-AP/BC	6 (16.2)	9 (15.0)
MDS	1 (2.7)	3 (5.0)
NHL	0 (0)	3 (5.0)
MPAL	1 (2.7)	1 (1.7)
Disease risk at first diagnosis (n, %)			0.78
High risk	30 (81.1)	51 (85.0)
Standard or intermediate risk	7 (18.9)	9 (15.0)
Disease stage in transplant (n, %)			0.68
CR1	25 (67.6)	37 (61.7)
≥CR2	7 (18.9)	9 (15.0)
Primary induction failure or no remission after relapse	5 (13.5)	14 (23.3)
Positive recipient CMV serology prior to transplant (n, %)	29 (78.4)	49 (81.7)	0.47
Conditioning regimens (n, %)			0.029
TBICY + HDAC	29 (78.4)	57 (95.0)
∗Others	8 (21.6)	3 (5.0)
GVHD Prophylaxis, n (%)
CSA + MMF	37 (100)	60 (100)
Neutrophil engraftment(days), median (range)	22 (14–65)	19 (12–42)	0.079
Platelet engraftment(days), median (range)	43 (21–115)	41 (18–75)	0.51
Follow-up among survivors, (months), median (range)	85 (48–130)	52 (38–102)

CBT, cord blood transplantation; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML-CP, chronic myeloid leukemia in chronic phase; CML-AP/BC, chronic myeloid leukemia in accelerated phase or blast crisis; MDS, myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; MPAL, mixed phenotype acute leukemia. CR, complete remission; CMV, cytomegalovirus; TBI, total body irradiation; CY, cyclophosphamide; HDAC, high-dose arabinoside cytarabine; GVHD, graft-versus-host disease; CSA, cyclosporine; MMF, mycophenolate mofetil.

^∗ Others included myeloablative BUCY2 plus HDAC (n = 1) and reduced intensity conditioning [fludarabine (150–165 mg/m²)+ busulfan (BU) (6.4 mg/kg) +low-dose TBI (3 Gy)+ antithymocyte globulin (7.5 mg/kg)] (n = 7) in double-unit CBT group, and myeloablative BUCY2 plus fludarabine (n = 3) in single-unit CBT group.

Table 2. Cord blood characteristics.

Characteristics	Double-unit CBT			Single-unit CBT	p*
	CB-1	CB-2	Combined
HLA match, no (%)					0.37
6/6	8 (21.6)	3 (8.1)	1 (2.7)	28 (46.7)
5/6	21 (56.8)	22 (59.5)	19 (51.4)	26 (43.3)
4/6	8 (21.6)	12 (32.4)	17 (45.9)	6 (10.0)
ABO compatibility, no (%)					0.086
Match	19 (51.4)	16 (43.2)	9 (24.3)	24 (40.0)
Major mismatch	8 (21.6)	7 (18.9)	11 (29.7)	21 (35.0)
Minor mismatch	10 (27.0)	14 (37.8)	17 (45.9)	15 (25.0)
Total nucleated-cell dose, median (range) (×10^7/kg) (infused)	2.51 (1.35–4.6)	2.02 (1.93–3.75)	4.53 (3.27–8.33)	3.29 (2.42–6.76)	<0.001
Total CD34+ cell dose, median (range) (×10^5/kg) (infused)	1.26 (0.85–5.12)	1.11 (0.45–3.67)	2.37 (1.29–8.78)	1.78 (1.05–4.95)	0.011

*p value was calculated by comparing combined double-unit grafts with single-unit graft in two groups.

The combined match score was the minimum HLA match between the first or second unit and the recipient (references [6,7]).

Figure 2. Neutrophil and platelet engraftment. The cumulative incidence of myeloid engraftment at 42 days was 89.2% (95%CI, 72.7–95.7%) in the double-unit CBT group, and 96.7% (95%CI, 86.9–99.2%) in the single-unit CBT group (p = 0.026) (a). The cumulative incidence of platelet engraftment at 100 days was 70.3% (95%CI, 51.2–81.9) in the double-unit CBT group, and 86.7% (95%CI, 74.6–93.0)] in the single-unit CBT group (p = 0.057) (b).

Figure 3. Acute GVHD and chronic GVHD. The cumulative incidences of grade II to IV aGVHD at day 100 in the double-unit CBT and the single-unit CBT groups were 23.4% (95%CI, 7.8–36.4) and 24.1% (95%CI, 12.3–34.4), respectively (p = 0.71) (a). The cumulative incidences of grade III to IV aGVHD in the corresponding group were 8.7% (95%CI, 0–17.7) and 12.1% (95%CI, 3.3–20.1), respectively (p = 0.59) (b). The cumulative incidences of cGVHD and extensive cGVHD at 5 year were 28.4% (95%CI, 5.8–45.5) and 19.9% (95%CI, 0.03–36.0) in the double-unit CBT group, and 24.4% (95%CI, 10.6–36.1) and 14.4% (95%CI, 2.9–24.4) in the single-unit CBT group, with no differences between the two groups (p = 0.72, 0.54) (c) and (d).

Figure 4. TRM and relapse. The 5-year cumulative incidence of TRM was significantly higher in the double-unit CBT group when compared with that of the single-unit CBT group [54.1% (95%CI, 36.5–68.7) vs. 33.3% (95%CI, 21.7–45.4), p = 0.026] (a). The 5-year relapse was 13.5% (95%CI, 4.8–26.8) in the double-unit CBT group and 11.7% (95%CI, 5.1–21.3) in the single-unit CBT group (p = 0.82) (b).

Table 3. Causes of death.

Mortality	Double-unit CBT (n = 25)	Single-unit CBT (n = 25)
Relapse (n, %)	4 (16.0)	6 (24.0)
Infection (n, %)	8 (32.0)	8 (32.0)
Acute graft-versus-host disease (n, %)	2 (8.0)	2 (8.0)
Chronic graft-versus-host disease (n, %)	3 (12.0)	5 (20.0)
Primary engraftment failure (n, %)	3 (12.0)	1 (4.0)
Fulminant hepatic failure with hepatitis B virus reactivation (n, %)	2 (8.0)	0 (0)
Intracerebral hemorrhage (n, %)	1 (4.0)	0 (0)
Cerebral infarction (n, %)	1 (4.0)	0 (0)
Thrombotic microangiopathy (n, %)	0 (0)	2 (8.0)
Others (n, %)	1 (4.0)	1 (4.0)

Others included one patient with suicide in double-unit CBT group, and one patient with Guillain-Barre syndrome in single-unit CBT group.

Figure 5. Survival. The 5-year probability of OS was 37.8% (95%CI, 22.6–53.0) in the double-unit CBT group, which significantly lower than that of the single-unit CBT group [56.7% (95%CI, 43.2–68.1)] (p = 0.037) (a). The 5-year probability of DFS in the double-unit CBT group [32.4% (95%CI, 18.2–47.5)] was significantly decreased compared with that in the single-unit CBT group [55.0% (95%CI, 41.6–66.5)] (p = 0.017) (b). The 5-year probability of GRFS was 24.3% (95%CI, 12.1–38.8) among double-unit recipients, which significantly lower than that among single-unit recipients [50.0% (95%CI, 36.8–61.8)] (p = 0.006) (c).

Wagner JE, Jr, Eapen M, Carter S, et al. Blood and marrow transplant clinical trials network. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014;371(18):1685–1694. doi: 10.1056/NEJMoa1405584

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Michel G, Galambrun C, Sirvent A, et al. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome. Blood. 2016;127(26):3450–3457. doi: 10.1182/blood-2016-01-694349

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