Patients 45 total; 32 Thal 35 Thal patients;

190 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

**MC CBT Jaing et al. [6]**

5 Re-CBT

Type of CB 100% MC CB 100% MC CB 100% MC CB 100% RCR CB

Age (yrs) Median 4.5 5.5 3.5 4

Pesaro class 1/2/3 21/9/0\* N/A N/A 9/2/4 N/A 2 20 HLA A/B/DR 6/6 11 8 26 5 5/6 25 16 48 14 ≤4/6 matches 27 28 53 16 TNC dose median 7.6 7.8 10.5 pre-freeze 6 Range 2.8–15.0 2.8–14.7 7.7 infused 2–32 CD34+ cell dose 4.0 4.0 3.7 N/A

% CB not washed 100% 100% 58% NA DCBT 13 DCBT 10 15 0

> 100% MC CB/ NW/±DCBT/CD34+

Myeloid ANC500 ANC500 88% ANC 88% ANC 87 ± 6% ANC500 42.8%

1 Secondary

F/U (M) median/range 26/3–66 36/6–76 6.5 21/3–138 Acute GvHD II–IV 76% 6 I; 12 II 0–II 38 ± 5% 23 ± 2%

**DFS 5Y 77.1% DFS 5Y 85.7% DFS 1 Y 72 ± 5%;**

**2Y TRM 12% 2Y TRM 11.7 ± 6.7% TRM 100 D 10 ± 3%;**

Priority

Platelet 20K (Plt20K) Plt 20K 82% Plt 20K 78% Plt 20K 81 ± 6%

Survival **OS 5Y 88.1% OS 5Y 88.3 ± 6.7% OS 1Y 79 ± 4%;**

Range 1.2–14 0.1–14

**MC CBT Petz et al. [5]**

100% MC CB/ NW/±DCBT

**3Y 79 ± 4%**

**3Y 70 ± 6%**

**3Y 20 ± 4%**

3 ± 2% 20/35

NA

57.2%

**OS 62 ± 9%**

**DFS 21 ± 7%**

120 total; 46 Thal 35 Thal

**RCR CBT Ruggeri et al. [3]**

> **Thal** = thalassemia major; **Other** = other nonmalignant indications; **CB** = cord blood; **CBT** = cord blood transplant; **MC** = non-red blood cell reduced cord blood MaxCell; **RCR** = red cell reduced cord blood; **SCBT** = single cord blood transplantation; **DCBT** = double cord blood transplantation; NW = non-wash post-thaw processing; **N/A** = not available; **GvHD** = graft-versus-host disease; **Ltd**. = limited chronic GvHD; **Ext** = extensive chronic GvHD; **TNC** = total nucleated cells in ×107 /kg patient weight; **CD34**+ = total CD34+ cells in ×105 /kg patient weight; **OS** = overall survival; **DFS** = disease-free survival; **TRM** = transplant-related mortality; **M** = months; **Y** = year; **D** = days post-transplant; **F/U** =  follow-up; **CI** = cumulative incidence; **KM** = Kaplan-Meier estimator survival; \* = Modified Pesaro (no liver biopsy), which may underestimate the disease severity; @ = TC data audited by CIBMTR on site.

**Table 2.** Unrelated CB transplantation for patients with thalassemia—large series—3 MC CBT and 1 RCR CBT.

From 2005 onwards, the Jaing-Chow collaboration reported their experience of a number of studies using unrelated CBT for thalassemia (**Tables 2** and **3**)—both Chang Gung Children Hospital single institution experiences [4, 6, 26, 31–35, 37, 51–53, 58] and multi-institutional studies from the StemCyte cord blood bank outcome database [5, 7, 35, 39, 42, 49, 54, 55]. The first thalassemia patient transplanted by Jaing's group on October 2003 became the first disease-free surviving CBT recipient in Taiwan [37].

A single institution series of unrelated CBT of 45 patients with nonmalignant diseases (32 thalassemia cases) was reported by Jaing's group in 2010 (**Table 2**). Most patients received HLA-mismatched CB grafts with median infused nucleated and CD34+ cell doses at 7.6 × 107 / kg and 4.0 × 105 /kg, respectively [26]. With cumulative incidence of neutrophil and platelet engraftment at 88 and 82%, four patients experienced primary graft failure. Three patients experienced grade IV acute GvHD and only a single patient suffered extensive chronic GvHD. Five-year OS and DFS were 88.1 and 77.1%, respectively, and TRM was 12% at 2 years.

To study the effect of RBC-replete MaxCell CB in a series of 58 thalassemia patients performed at nine U.S. and five non-U.S. transplant centers, Chow's group [33] compared 48 patients who received MaxCell CB versus 10 patients who received RCR CB (**Table 3**). Though this initial study was not rigorously matched, patients were similar among two groups in age, weight, disease severity, TNC dose, #HLA matches, conditioning regimen, no post-thaw wash, and transplant center experience. There were more double CBTs in the MaxCell group (23 versus 10%). The raw comparison results between the two groups showed no significant differences in cumulative incidence in neutrophil (MaxCell 96 ± 4% vs. RCR 75 ± 15%; RR = 1.31; p = 0.56) or platelet 50K engraftment (MaxCell 95 ± 5% vs. RCR 75 ± 15%; RR = 1.24; p = 0.64). Overall patient survival at 1-year trended higher for MaxCell CBT (MaxCell 89 ± 6% vs. RCR 53 ± 20%; RR = 0.32; p = 0.17); however, importantly, DFS was significantly higher at 89 ± 6% for MaxCell CB compared to 38 ± 17% (RR = 0.17; p = 0.01).



**Jaing et al. 2008 matched pair (MP) MC CB ARM @ [32–34]**

58 Thal patients 48 MC patients

pairs

CSA MP

Range Pre-match 2.5–47

MP 3.4–20

0.92)

0.73) Graft failure **MP 1Y MC 7 ± 5%;**

**RCR 22 ± 14%**

Age (yrs) median Pre-match 5.0

Range Pre-match 0.3–20

patients

post-MP 4.0

post-MP 0.3–12

MP performed on 30 matched

192 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

30 MC patients vs. 10 RCR
