Page 1850 - Hematology_ Basic Principles and Practice ( PDFDrive )

1646 Part X Transplantation

TABLE Potential Strategies to Enhance Cord Blood Engraftment
107.4
Median Age Platelet Engraftment
Strategy Reference Protocol Patients (n) (year) Neutrophil Engraftment (≥20,000/mm ) Outcomes
3
Coinfusion Bautista et al 113 Single CB units + 55 34 96%; median ANC, 10 78%; median time, 32 DFS 47% and OS
of HSC coinfusion of TCD HSC days (9–36 days) days (13–98 days) 56% at 5 years
from haploidentical or
third-party donors
Liu et al 114 Single CB units + 45 50 95%; median ANC 11 83%; median time, 19 PFS 42% and OS
coinfusion of TCD HSC days (9–15 days) days (15–33 days) 55% at 1 year
from haploidentical
related donors
Stem cell de Lima et al 115 CB ex vivo expansion 10 21 Median ANC, 30 days Median, 48 days 30% survival at
expansion with copper chelator (16–46 days); 9/10 (35–105 days) in 25 months
TEPA patients engrafted 6/10 patients
Stiff et al 116 CB ex vivo expansion 101 37 21 days 54 days Improved survival
with copper chelator at day 100
TEPA compared with
controls
Delaney et al 56 Notch-mediated 10 27 Median ANC, 16 days Unknown 7/10 alive
+
expansion of CD34 (7–34 days); 1
cells patient had primary
graft rejection
de Lima et al 117 CB ex vivo expansion 32 35 97%; median ANC, 15 Median, 40 days OS 40% at 5
with MSC days (9–42 days) (13–62 days) years
Horwitz et al 118 Nicotinamide 11 45 Median ANC, 13 days Median, 33 days OS 82%
PFS 73%
Wagner et al 119 SR1
Stem cell Campbell et al 120 CD26 inhibition N/A (mice) N/A Significant increase in Unknown N/A
homing Christopherson engraftment
et al 121,122
Cutler et al 123 CB treated with PGE 2 9 43 Median ANC, 24 days Median, 72.5 days 2 graft failures
Cohort 1 in 7/9
12 57.5 Median ANC, 17.5 Median, 43 days No graft failure
CB treated with PGE 2
Cohort 2 days (14–31 days) (20–60 days)
Popat et al 124 Fucosylation of CB CD34 22 42 Median ANC, 17 days Median, 35 days 1 patient died
+
cells (12–34 days) (18–100 days) from sepsis on
day 23; 1 had
secondary graft
failure.
ANC, Absolute neutrophil count; CB, cord blood; DFS, disease-free survival; HSC, hematopoietic stem cell; MSC, mesenchymal stem cell; N/A, not applicable; OS, overall
survival; PGE 2, prostaglandin E 2; PFS, progression-free survival; TCD, T cell depleted; TEPA, tetraethylenepantamine.

113
unmatched third-party donor to support single-unit CBT. This A recent study from the MSKCC assessed the use of DCBT
series included 55 patients with high-risk hematologic malignancies. combined with haploidentical CD34+ cells in 39 patients (median
126
The median time to neutrophil recovery was 10 days, and the 48 years) after myeloablative (n = 2) or RIC (n = 37). The median
7
7
maximum cumulative incidence of neutrophil engraftment was 96%; infused TNC dose of CB units was 2.30 × 10 /kg and 1.86 × 10 /
3
the median time to platelets greater than 20,000/mm was 32 days kg and the median infused CD34+ cell dose from haploidentical
6
with an incidence of 78%. The cumulative incidence of full CB donors was 3.1 × 10 /kg. One patient with DSAs to the haploidential
chimerism was 91% and took a median of 44 days. Grade II–IV acute and both CB units had graft rejection. In the remaining evaluable
GVHD developed in 10 patients and grade III–IV acute GVHD in patients, the median time to neutrophil engraftment was 13 days
6 patients. Twenty-two patients died (3 relapses, 6 organ failures, 4 (range 11–38), one of which had graft rejection at a later time. All
GVHD, 8 infections, 1 graft failure). The 5-year OS and DFS were of the remaining 36 patients had sustained CB engraftment and
56% and 47%, respectively. The van Besien group recently reported rejected the haploidentical graft at some point. In these patients,
similar findings that included 45 patients with hematologic malig- haploidentical graft contributed to either bridge engraftment without
nancies (47% had refractory or untreated relapse) who received RIC transient neutropenia (n = 20), bridge engraftment with transient
+
followed by transplantation of a single CB unit and CD34 cells from neutropenia (n = 5), or no engraftment (n = 11). One of the signifi-
114
a haploidentical donor. Rapid engraftment was obtained with cant complications noted in the study was occurrence of preengraft-
3
cumulative incidences for neutrophil and platelet (>20,000/mm ) ment syndrome in 76% of patients, which was severe in 8%, but
engraftment of 95% at day 50 and 83% at day 100, respectively, with responded to steroids in all cases. 126
a median time to recovery of 11 days for neutrophils and 19 days for Ex vivo CB expansion is another approach to enhance neutrophil
platelets. However, the percentage of host-derived hematopoiesis was recovery. Given that cellular copper has been implicated in the regula-
+
−
5% by day 180, and four patients had graft failure (2 primary and 2 tion and differentiation of HSCs, Peled et al 127,128 cultured CD34 38
secondary). The cumulative incidence of grade II–IV acute GVHD CB HSCs with a copper chelator tetraethylenepentamide (TEPA). A
was 25%, and the 1-year OS and progression-free survival (PFS) rates group of investigators at the MDACC conducted a phase I/II clinical
were 55% and 42%, respectively. trial in which CD133+ selected CB hematopoietic progenitors from