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Selection of an umbilical cord blood graft for hematopoietic cell transplantation

Selection of an umbilical cord blood graft for hematopoietic cell transplantation
Author:
Nelson J Chao, MD
Section Editor:
Robert S Negrin, MD
Deputy Editor:
Alan G Rosmarin, MD
Literature review current through: Jan 2024.
This topic last updated: Apr 07, 2022.

INTRODUCTION — Allogeneic hematopoietic cell transplantation (HCT) is an important and potentially curative treatment option for a variety of malignant and nonmalignant diseases. Human leukocyte antigen (HLA)-matched sibling donors (MSD) are the preferred graft source for allogeneic HCT, but most transplant candidates do not have a suitable HLA-identical MSD. For patients without a suitable MSD donor, identifying an unrelated donor through a national registry is a lengthy process that is not always successful, especially for individuals who are not of Northern European descent.

Umbilical cord blood (UCB), the blood remaining in the umbilical cord and placenta following the birth of an infant, is an alternative graft source for allogeneic HCT. The relative ease of procurement, increased representation of ethnic minorities, and ability to use partially HLA-matched UCB units significantly expands the HCT donor pool. Use of lower-intensity conditioning regimens can facilitate engraftment of UCB and broadens the scope of patients who may benefit from allogeneic HCT, including older or less medically-fit patients. Approximately 35,000 UCB transplants were performed through 2020 and nearly three-quarters of a million UCB units are available worldwide through >100 UCB banks [1].

The advantages and limitations of UCB and the selection of an umbilical cord blood graft are discussed in this topic.

Use of UCB transplantation in adults using myeloablative and NMA regimens, and the collection, storage, and ethical issues regarding the use of UCB for HCT are discussed separately.

(See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

(See "Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens".)

(See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)

(See "Donor selection for hematopoietic cell transplantation".)

FEATURES OF UCB GRAFTS — UCB is the blood remaining in the umbilical cord and placenta following the birth of an infant. UCB can provide the hematopoietic stem and progenitor cells that are needed for allogeneic HCT in patients who do not have a human leukocyte antigen (HLA)-matched related or unrelated donor.

UCB transplantation (UCBT) from a related or unrelated donor is a well-accepted hematopoietic graft source in pediatric patients with hematologic malignancies, marrow failure, or metabolic syndromes. However, for allogeneic HCT in adults, relatively limited numbers of hematopoietic stem and progenitor cells in UCB units can impair engraftment and immune reconstitution, which are associated with unfavorable HCT outcomes.

Increased demand for UCBT — There has been increased use of UCBT due to several factors, most of which address limitations encountered in the use of HLA-matched unrelated donor (MUD) graft. In some settings, increased use of haploidentical transplantation using post-transplant cyclophosphamide has reduced or reversed the trend toward greater use of UCBT.

Demand for UCBT has increased due to:

Lack of suitable HLA-matched donors – Most patients do not have an HLA-identical relative, since each full sibling potential donor has only a 25 percent chance of being fully HLA-matched. A search for a MUD with ≥9/10 high-resolution HLA match is successful for approximately 80 percent for individuals of Northwestern European descent, but much lower for other ethnic groups [2]. (See "Donor selection for hematopoietic cell transplantation", section on 'Unrelated donors'.)

Donor attrition – Despite large lists of volunteer donors worldwide, a significant percentage of donors will no longer be available for donation when needed.

Time constraints – Identifying, typing, and harvesting an unrelated donor is cumbersome and lengthy process, with the median time interval between initiation of a search and the donation of marrow of about two to four months; a search can be expedited if necessary [3]. A preliminary search usually provides insight into how likely it will be to identify a donor for an individual patient.

Graft-versus-host disease (GVHD) – HLA disparities when using bone marrow and peripheral blood graft sources are associated with increased GVHD [4-6].

Advantages — Advantages for the use of UCB grafts include:

Expanded donor pool – Increased representation of ethnic minorities in the unrelated UCB banks and the ability to use partially HLA-matched UCB units significantly expands the donor pool [2]. (See 'HLA type' below.)

Ease of procurement and lack of donor attrition – UCB can be tested prior to storage for infections, blood and HLA-type, and cell dose, thereby making the specimen more rapidly available [7]. Likewise, storage of UCB avoids the risk of donor attrition. Together, these characteristics result in a shorter time to UCBT, compared with unrelated bone marrow or peripheral blood grafts [8]. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

Favorable outcomes – The incidence and severity of acute and chronic GVHD in recipients of HLA-disparate unrelated UCB grafts are lower than those associated with MUD or partially-matched related bone marrow grafts [9]. UCBT is associated with similar overall survival (OS) and improved GVHD-free/relapse-free survival (GRFS), compared with matched related or unrelated grafts [10-12]. (See 'Outcomes' below.)

Safety for donors and recipients – UCB is relatively easy to collect after the delivery of a newborn and does not put the mother or newborn at risk. In addition, there is a reduced likelihood of transmitting infections (eg, cytomegalovirus) from the donor to the recipient.

High proportion of engraftable cells – UCB units usually have fewer total nucleated cells (TNC) and CD34+ cells compared with a graft from bone marrow or peripheral blood. However, the proportion of engraftable cells (eg, primitive hematopoietic progenitor cells and multipotent colony-forming cells) in UCB is higher and the cells have greater higher self-renewal capacity, shorter cell cycle times, longer telomeres, and higher in vivo hematopoietic reconstitution capacity in animal models [13-19].

Disadvantages — The main limitations of UCB as an HCT graft source are:

Increased risk of graft failure – UCB contains limited numbers of hematopoietic stem and progenitor cells; as a result, single UCB samples may contain an insufficient cell dose to reconstitute the bone marrow of a large child or adult. (See 'Cell dose' below.)

Increased infections – UCBT is associated with more infectious complications, but not with more infection-related deaths, compared with unrelated donor bone marrow or peripheral blood grafts [20]. The increase in infections is associated with slower neutrophil recovery and other effects on immune reconstitution, which may be related to use of antithymocyte globulin (ATG) [21]. UCBT is associated with a longer median duration of neutropenia (30 versus 14 days), but not with an increase in infection-related deaths [22]. (See "Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens", section on 'Toxicity and transplant-related mortality'.)

Unavailability for additional donations – The donor is not available for subsequent donor lymphocyte infusions or other cell-based therapies.

Possible transplantation with a hematologic disorder – UCB samples are evaluated with a blood film and hemoglobinopathy screening prior to storage but, theoretically, there remains an increased risk of transmitting undetected hematologic diseases [23].

Incidence of post-HCT autoimmune disorders – For patients who are transplanted for non-malignant disorders, the cumulative incidence of a new autoimmune disease after UCBT appears to be at least as high as other alternative donor sources. A registry study reported new autoimmune illnesses in 5 percent at one year and 7 percent at five years, with autoimmune hemolytic anemia, immune thrombocytopenia, and Evans syndrome being most common [24].

UCB UNIT SELECTION — The main criteria for selecting UCB unit(s) for transplantation are the human leukocyte antigen (HLA) haplotype and the total nucleated cell (TNC) dose per kilogram (kg) of recipient body weight.

Selection criteria — We consider the following criteria for choosing a UCB graft:

Closest HLA match – ≥4/6 HLA match (HLA-A, -B, -DRB1) or ≥4/8 match (HLA-A, -B, -C, -DRB1) (see 'HLA type' below)

Cell dose – Either of the following:

≥3 x 107 TNC/kg of recipient body weight

or

≥2 x 105 CD34+ cells/kg recipient body weight (see 'Cell dose' below)

Potential UCB units with the greatest HLA-match that have an acceptable TNC count should be chosen. Cryopreservation of UCB cells does not require discarding any type of cells prior to freezing and the cells should not be washed or otherwise handled after thawing (to avoid loss of stem and progenitor cells) [25].

When no single UCB unit satisfies both selection criteria, options include use of two UCB units (double UCB transplantation; dUCBT), ex vivo expansion, or alterations in the conditioning or immunosuppressive regimens. For dUCBT, the two units should have a combined dose of ≥3 x 107 TNC/kg. If possible, there should be ≤1 HLA difference between the UCB units and the patient. In patients without a malignant disease, the cell doses should be higher or the HLA incompatibility lower. (See 'Strategies for inadequate cell dose' below.)

A "backup graft" should be available in case of unexpected problems when the selected UCB unit thaws or if it fails to engraft [26]. The backup unit is reserved at the UCB bank until the patient has engrafted; after engraftment, the reservation is cancelled. Collection of autologous hematopoietic progenitor cells as a backup graft for patients at higher risk of graft failure does not appear to be necessary, especially in patients with a 6 of 6 HLA-match who are undergoing myeloablative UCB transplantation [27].

HLA type — Matching donor and recipient for HLA class I (-A, -B, and -C) and class II (-DRB1 and -DQ) haplotypes is a key part of successful UCB transplantation (UCBT). Units with the greatest similarity in HLA haplotype to the recipient and sufficient cell dose should be selected. However, compared with other alternative donor sources, such as bone marrow (BM) or peripheral blood (PB) grafts from unrelated donors, UCBT can be performed using less-stringently matched grafts.

Most UCB banks evaluate UCB samples using serologic testing for HLA-A and HLA-B and molecular typing for HLA-DRB1. Using this method, units that are matched at 4, 5, or 6 of 6 HLA alleles are acceptable sources; UCB units with HLA-matches ≤3/6 are not acceptable because such units are associated with high treatment related mortality (TRM) and low rates of disease-free survival (DFS) [28,29]. When available, additional matching for HLA-C improves patient outcomes. This testing approach differs from that used for unrelated donor BM or PB graft matching, in which molecular typing of 10 HLA alleles is preferred and acceptable donors are generally limited to ≤1 HLA-mismatch [30].  

Once a UCB unit has been selected for transplantation, HLA-typing must be confirmed on an attached or contiguous segment of the product. The importance of confirmatory HLA-typing was illustrated by a study that reported that 2 of 871 UCB units (0.2 percent) sent to a single medical center for HCT were mislabeled and potentially would have been transplanted incorrectly [31].

HLA-matching – Although UCBT is associated with higher TRM, rates of acute and chronic graft-versus-host disease (GVHD) are generally lower than with BM or PB grafts for HCT. UCB units with ≥4 of 6 HLA match produce outcomes that are at least as good as an 8 of 8 HLA-matched BM for HCT in children with a malignancy. (See 'UCB versus matched sibling donor' below.)

The degree of HLA mismatch can affect UCBT outcomes. In a retrospective analysis of 803 patients (up to age 62 years) with leukemia or a myelodysplastic syndrome (MDS), compared with patients matched at 8 HLA loci (ie, HLA-A, -B, -C, -DRB1), TRM was increased for patients mismatched at two HLA loci (ie, 6 of 8 HLA match; hazard ratio [HR] 3.27 [95% CI 1.42-7.54]), three loci (HR 3.34 [95% CI 1.4-7.71]), or four loci (HR 3.51 [95% CI 1.44-8.58]) loci [32]. Patients mismatched for HLA-C, also had higher TRM, whether they were matched at HLA-A, -B, and -DRB1 (HR 3.97, 95% CI 1.27-12.40) or had a single mismatch at HLA-A, -B, or -DRB1 (HR 1.70 [95% CI 1.06-2.74]). Similarly, mismatching for HLA-DRB1 increased TRM among patients mismatched at a single HLA-A, -B, or -C locus.

In a retrospective study of children with acute leukemia who underwent myeloablative conditioning (MAC), outcomes were compared between 503 children given an unrelated mismatched UCBT versus 282 children who received a matched unrelated donor (MUD) BM graft [33]. HLA-mismatched BM recipients had more acute and chronic GVHD, without improving leukemia-free survival (LFS). Five-year LFS was higher in children who received 6 of 6 HLA-matched (HLA-A,-B,-DRB1) UCBT than in children who received 8 of 8 (HLA-A,-B,-C,-DRB1) matched BM transplants (60 versus 38 percent). There was a trend toward decreasing five-year LFS with increasing UCB HLA-disparity.

Similar results were also reported in other studies [34-39].

Other matching – The importance of other matching of donor and recipient is less well-defined:

KIR gene matching – The killer-cell immunoglobulin-like receptor (KIR) gene encodes natural killer cell immunoglobulin-like receptors that recognize epitopes of HLA-A, HLA-B, and HLA-C (so-called KIR ligands) and may impact outcomes after UCBT [40]. (See "Donor selection for hematopoietic cell transplantation", section on 'KIR gene haplotype'.)

Recipient HLA antibodies – HLA-mismatched units that contain HLA determinants for which the recipient has pre-formed HLA antibodies should be avoided [41]. If donor-specific antibodies are detected, the unit should not be used, or the recipient should be treated to remove the antibodies. (See "Donor selection for hematopoietic cell transplantation", section on 'Donor-specific HLA antibodies'.)

Cell dose — Cell dose can be assessed according to either TNC/kg recipient body weight or CD34+ cells/kg recipient body weight. Clinically important outcomes, including the incidence of graft failure and speed of bone marrow recovery, correlate with TNC dose/kg [28,42]. Higher doses are required for engraftment of UCB units with greater HLA-disparity. However, the ideal cell dose for UCBT is not well-defined and progenitor cell measurements are not standardized among UCB banks.

In general, units should have ≥3 x 107 nucleated cells/kg or ≥2 x 105 CD34+ cells/kg. The risk of graft rejection is higher in patients who undergo UCBT for non-malignant diseases, and a dose of ≥3.5 x 107 nucleated cells/kg has been suggested, based on poor survival if lower TNC doses were administered [38].

Actual recipient body weight should be used, rather than ideal or adjusted body weight. All UCB units should have a TNC dose measured prior to cryopreservation. Although less commonly provided, a measure of CD34+ cells [43] can be used; colony forming units (CFUs) are now rarely used [44-46]. Successful engraftment generally requires ≥3 x 107 TNC/kg or ≥2 x 105 CD34+ cells/kg [29,39] and, if two UCB units are used, each individual unit should have ≥2.0 x 107 TNC/kg [26]. (See 'Double UCBT' below.)

Retrospective studies have illustrated the importance of cell dose on outcomes with UCBT [33,39,43,47,48].

In an analysis of 1568 patients who received single-unit MAC UCBT for leukemia or MDS, those who received <3 x 107 TNC/kg had 15 to 20 percent higher non-relapse mortality (NRM) than those who received TNC ≥3 x 107 per kg [39]. Selection of a unit with TNC >5 x 107 per kg did not further decrease NRM for those with ≥5 of 8 HLA match; however, TNC >5 x 107 per kg was associated with decreased NRM among those with a 4 of 8 HLA match.

TRM increased with decreasing TNC dose and increasing HLA-disparity in analysis of 1061 patients who received a single-unit UCBT with MAC for leukemia or MDS [29]. The highest rates of TRM were seen for patients who received a unit with TNC <2.5 x 107/kg, regardless of HLA-disparity; conversely, TRM was lowest for 6 of 6 HLA-matched units regardless of TNC dose. TRM rates were similar for patients who received either a 5 of 6 HLA-matched unit with a TNC 2.5-5 x 107/kg or a 4 of 6 HLA-matched unit with a TNC of ≥5 x 107/ kg. Higher TRM was seen for patients who received a 4 of 6 HLA-matched unit with a TNC between 2.5-5 x 107 per kg.

Higher TRM was reported for children who received TNC <3 x 107/kg with one HLA disparity and for children given a two HLA-disparate UCBT (independent of cell dose) in an analysis of UCBT in 503 children with acute leukemia [33].

Other factors — Other factors that may influence UCB unit selection include the following:

Bank of origin – UCB banks that are accredited by NetCord-FACT are preferred. UCB quality, reliability of unit information, turnaround time, fees, and communication may vary from bank to bank [49].

RBC content – UCB units are typically processed prior to freezing to remove red blood cells (RBC), plasma, or both. UCB samples that have not had RBC-depletion should be washed prior to administration to remove RBC debris and free hemoglobin that may cause significant infusion reactions. Unprocessed UCB units typically contain more dimethyl sulfoxide (DMSO).

Infectious disease monitoring – Donor mothers should be screened for hepatitis B, HIV, syphilis, HTLV-1, HTLV-2, and cytomegalovirus [26]. UCB units should be analyzed for sterility with bacterial and fungal cultures. In addition, more recently collected units are also tested for West Nile virus and Chagas disease.

Hematologic disease screening – Prior to storage, UCB should be screened for hematologic diseases with a blood film and hemoglobinopathy screening. Units with normal hemoglobin analysis and those with hemoglobin F are acceptable. If no other UCB units are suitable, use of UCB units that are heterozygous for either sickle cell disease (ie, sickle cell trait) or thalassemia (but not both) may be considered [26].

Age of stored unit – There is no accepted "shelf life" for UCB units and outcomes using older units appear to be equal to those with shorter storage duration. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation", section on 'Shelf-life of units'.)

STRATEGIES FOR INADEQUATE CELL DOSE — Single UCB units often have insufficient cell dose for reconstitution of the bone marrow of a large child or adult (eg, >70 kg). Several strategies can be employed when the cell dose is insufficient for UCB transplantation (UCBT), but the preferred approach varies among institutions.

Double UCBT — Double UCBT (dUCBT; ie, infusion of two UCB units) is acceptable for recipients without a single UCB unit of adequate cell dose, but single-unit UCBT (sUCBT) is generally preferred. Although graft acquisition costs and graft-versus-host disease (GVHD) may be increased with dUCBT, more adult patients receive dUCBT than sUCBT [50].

Compared with adequately-dosed sUCBT, patients receiving dUCBT generally have similar overall survival (OS), higher rates of grade ≥2 acute GVHD (aGVHD), and modestly delayed engraftment, but may have fewer relapses [51-53].

When two UCB units are infused, there may be a transient chimerism (ie, hematopoietic cells from both grafts are present), followed by the sustained dominance of one of the units by day 100 [54]. A prolonged state of mixed chimerism is more common in patients receiving less intensive preparative regimens [55].

Outcomes using dUCBT include:

A phase 3 trial randomly assigned of 224 children (<21 years) undergoing myeloablative conditioning (MAC) HCT to either sUCBT versus dUCBT [53]. After a median follow-up of 27 months, both trial arms achieved similar one-year OS (65 percent for dUCBT versus 73 percent for sUCBT) and comparable disease-free survival (DFS), time to neutrophil recovery, infections, and grade ≥2 aGVHD. However, sUCBT was associated with improved platelet recovery, less grade ≥3 aGVHD (13 versus 23 percent), and a lower incidence of extensive chronic GVHD (9 versus 15 percent).

Another phase 3 trial reported that dUCBT did not decrease transplant strategy failure (a composite endpoint of transplant-related mortality [TRM], engraftment failure, and autologous recovery), but was associated with higher rates of GVHD and delayed relapses [56]. A follow-up analysis reported that dUCBT may enhance the graft-versus-leukemia effect and survival in patients with measurable residual disease [57].

A retrospective study reported that dUCBT was associated with better outcomes and was more cost-effective for adults with acute leukemia in first CR; however, unlike other studies, this report did not require TNC ≥2.5 x 107 TNC/kg for patients undergoing sUCBT [58]. Compared with sUCBT (61 patients), dUCBT (73 patients) was associated with superior OS (62 versus 42 percent) and two-year leukemia-free survival (LFS; 53 versus 33 percent), but more grade ≥2 aGVHD (52 versus 34 percent); there was no difference in grade ≥3 aGVHD. Neutrophil engraftment occurred in 78 versus 69 percent for dUCBT and sUCBT, respectively, and there was no difference in non-relapse mortality (NRM). Another study also reported fewer relapses in association with dUCBT [59] and a retrospective review of 97 patients (age ≥14 years, ≥50kg) reported that dUCBT group was associated with lower five-year TRM (54 versus 33 percent) and GVHD-free/relapse-free survival [60].

Some experts suggest that UCB units should share ≥3 of 6 human leukocyte antigen (HLA)-match with one another, while others do not place limits on the unit-to-unit match. Retrospective analyses have not demonstrated a relationship between unit-to-unit HLA match and the likelihood of sustained donor engraftment [26,61]. The dominant graft cannot be predicted based upon the respective doses, level of CD3+ cells, cell viability, degree of HLA-match, ABO group, sex of donor, or order and route of infusion [20]. A single-institution series of 84 recipients of dUCBT reported that the unit with the higher dose was more likely to become dominant and that a high level of unit-to-unit HLA match was associated with an increased likelihood of engrafting both UCB units [61].

Improving cell dose — Ex vivo expansion of cell dose and supplementation with a limited number of mobilized peripheral blood stem and progenitor cells (PBSPC) from an HLA-unrestricted third party donor or haploidentical donor (ie, dual transplants) have been used to enhance the cell dose for UCBT.

Ex vivo expansion – Ex vivo expansion of UCB stem and progenitor cells prior to transplantation may shorten the period of hematopoietic recovery and hasten immune reconstitution associated with UCBT. Nicotinamide has been shown to expand committed and long-term repopulating stem and progenitor cells and increase bone marrow homing and engraftment potential [62-64].

In a phase 3 trial, a nicotinamide-expanded cell product from a single banked UCB specimen achieved faster engraftment and reduced infections compared with standard UCB product; there was no difference in GVHD or overall survival [65]. Patients undergoing myeloablative conditioning (125 patients, 13 to 65 years) were randomly assigned to the ex vivo expanded product (Omidubicel) versus standard single or double UCB grafts. The expanded product achieved significantly faster median time to neutrophil engraftment (10 versus 20 days) and platelet engraftment (37 versus 50 days), with less primary graft failure (2 versus 10 percent). There was no significant difference in the incidence of acute GVHD or chronic GVHD, non-relapse mortality, or relapse. Patients receiving the expanded product had fewer grade ≥3 bacterial/fungal infections (37 versus 57 percent), were discharged sooner (median 27 versus 35 days) and spent more of the first 100 days alive and out-of-hospital (61 versus 48 days). Another study also reported that patients who received ex vivo nicotinamide-expanded UCB grafts experienced faster engraftment and fewer infections compared with historical controls [66].

Other methods for ex vivo expansion have also been explored [67-72].

Dual transplant – Infusion of mobilized PBSPCs from a nonmaternal HLA-haploidentical relative may facilitate durable engraftment of single UCB units in adults [73,74]. In one study, 45 patients received a reduced intensity conditioning regimen followed by infusion of a matched UCB unit and HLA haploidentical PBSPCs [74]. Most patients demonstrated early transient haploidentical engraftment followed by permanent UCB engraftment with or without evidence of minor host- or haploidentical-derived hematopoiesis. The median times to neutrophil and platelet engraftment were 11 and 19 days, respectively. The cumulative incidences of acute and chronic GVHD were 25 and 6 percent at one year.

OUTCOMES — UCB transplantation (UCBT) is associated with excellent overall survival (OS), a low incidence of chronic graft-versus-host disease (GVHD), and favorable GVHD-free/relapse-free survival (GRFS) compared with HCT using matched-related or unrelated grafts. However, graft failure or delayed engraftment, increased transplant-related mortality (TRM), and more infectious risk remain important challenges.

UCB versus matched sibling donor — UCBT is associated with more GVHD, but lower rates of relapse and better GRFS compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) HCT.

Unrelated UCBT was compared with MSD grafts for HCT using a myeloablative conditioning (MAC) regimen in children and adults with acute myeloid leukemia (AML) [10]. Compared with 55 patients who underwent MSD HCT, 107 patients who received a single unit UCBT had no differences in TRM, grade ≥2 acute GVHD (aGVHD), or grade ≥3 acute aGVHD. UCBT was associated with a lower incidence of relapse, better GRFS, and a lower incidence of chronic GVHD (cGVHD) and extensive cGVHD.

A retrospective study compared outcomes among 190 adult patients undergoing double-unit UCBT (dUCBT) versus 123 adults receiving MSD HCT [11]. OS was comparable between cohorts, but GRFS was superior for UCBT patients, primarily due to decreased moderate to severe cGVHD.

UCB versus matched unrelated or mismatched unrelated donor — Leukemia-free survival (LFS) after dUCBT transplantation is comparable with that after MSD and matched unrelated donor (MUD) HCT.

In patients with measurable residual disease (MRD) with AML or myelodysplastic syndrome (MDS), UCBT was associated with a lower rate of relapse than MUD and mismatched unrelated donor (mMUD) HCT in a retrospective analysis of 582 patients [75]. The relative risks of death and relapse varied according to MRD status prior to HCT; however, among patients with MRD, the rate of OS with UCBT was at least as favorable as MUD HCT and was higher than OS after mMUD HCT.

A multicenter retrospective study compared outcomes with acute leukemias after UCBT (79 patients) versus HCT using unrelated peripheral blood stem and progenitor cell transplantation (PBSPC; 96 patients) [12]. aGVHD, TRM, OS, and LFS were similar between groups, but UCBT recipients had higher three-year GRFS and performance status, less moderate/severe cGVHD, and lower incidence of Epstein-Barr virus (EBV) viremia and post-transplantation lymphoproliferative disease (PTLD).

Another retrospective study reported outcomes after MAC HCT for hematologic malignancies using MSD (204 patients), MUD (152 patients), one antigen-mismatched mMUD (52 patients), or ≥4 of 6 HLA-matched dUCB (128 patients) [76]. Five-year LFS was similar for each donor type (ranging from 33 to 51 percent), but compared with other donor sources, dUCB was associated with a lower risk of relapse (15 versus 35 to 43 percent) yet higher rates of non-relapse mortality (NRM; 34 versus 14 to 24 percent).

UCB versus haploidentical HCT — UCBT is associated with similar OS compared with HCT using a haploidentical graft (eg, from a parent or child), but rates of NRM and relapse differ.

A multicenter phase 3 trial (BMT CTN 1101) reported no difference in platelet recovery, grade ≥2 aGVHD and grade ≥3 aGVHD, cGVHD, or rate of relapse [77]. There was no difference in two-year progression-free survival (PFS) between the donor sources, but UCBT recipients had delayed neutrophil recovery, increased TRM, and decreased OS.

A study compared outcomes of 50 patients who underwent reduced intensity conditioning (RIC) dUCBT versus 50 patients who received RIC haploidentical donor bone marrow transplant for leukemia or lymphoma [78]. Rates of OS and PFS were similar for both groups; UCBT was associated with 54 percent one-year OS and 46 percent one-year PFS, while the corresponding rates for haploidentical HCT were 62 and 48 percent. For dUCBT, one-year NRM was 24 percent, compared with 7 percent with haploidentical HCT, and one-year relapse rates were 31 and 45 percent, respectively.

UCB RESOURCES — UCB banks have been established for related and unrelated UCB transplantation (UCBT), with several hundred thousand units available in >100 cord blood banks worldwide (wmda.info) [23,79,80]. Procedures and quality standards for the safe collection, processing, testing, storage, selection, exchange, and clinical use of UCB are provided by NetCord-Foundation for the Accreditation of Cellular Therapy (www.factwebsite.org). (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation".)

SUMMARY

Umbilical cord blood (UCB) – UCB is the blood remaining in the umbilical cord and placenta following the birth of an infant. UCB has emerged as an alternative graft source for allogeneic hematopoietic cell transplantation (HCT) in children and adults.

Advantages and disadvantages – Compared with other alternative donor sources, UCB transplantation (UCBT) can expand the donor pool, facilitate graft procurement, lacks donor attrition, and is associated with decreased graft-versus-host disease (GVHD). However, UCBT is associated with an increased risk for graft failure, delayed immune reconstitution, and unavailability of the donor for additional donations (ie, donor lymphocyte infusions). (See 'Features of UCB grafts' above.)

UCB unit selection – The main criteria for selecting UCB unit(s) for transplantation are the human leukocyte antigen (HLA) haplotype and the cryopreserved total nucleated cell (TNC) dose per kilogram recipient body weight.

We select UCB unit(s) according to the following criteria:

Closest HLA match – ≥4/6 HLA match (HLA-A, -B, -DRB1) or ≥4/8 match (HLA-A, -B, -C, -DRB1) (see 'HLA type' above)

Cell dose – ≥3 x 107 TNC/kg or ≥2 x 105 CD34+ cells/kg (see 'Cell dose' above)

Other factors – The UCB bank of origin, red blood cell content, age of the stored unit, and screening for infectious and hematologic diseases may also influence selection. (See 'Other factors' above.)

Inadequate cell dose – If single UCB units have insufficient cell dose for a large child or adult (eg, >70 kg), the preferred approach varies among institutions, but options include:

Double umbilical cord transfusion. (See 'Double UCBT' above.)

Ex vivo expansion or supplementation with mobilized peripheral blood stem and progenitor cells (PBSPCs) from a nonmaternal HLA-haploidentical relative. (See 'Improving cell dose' above.)

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Topic 16563 Version 29.0

References

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