Research Advances

By Karen Ballen, MD, Michael Horwitz, MD, Junya Kanda, MD, PhD, and Elisabetta Xue, MD
Updated:  February 2021


High Progression-Free Survival after Intermediate Intensity Double Unit Cord Blood Transplantation in Adults

Barker J et al, Blood Advances, 2020
Memorial Sloan Kettering Cancer Center, New York, NY, USA

Cord blood transplantation (CBT) after high intensity or nonmyeloablative conditioning has limitations.
Methods: The study investigated cyclosporine-A/mycophenolate mofetil-based intermediate intensity (cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 10 mg/kg, total body irradiation 400 cGy) unmanipulated double-unit CBT (dCBT) with prioritization of unit quality and CD34+ cell dose in graft selection.
Findings: The cumulative incidences of sustained CB engraftment, day 180 grade III-IV acute, and 3-year chronic graft-versus-host disease were 99%, 24%, and 7%, respectively. Three-year transplant-related mortality and relapse incidences were 15% and 9%, respectively. Three-year overall survival is 82%, and progression-free survival (PFS) is 76%. In 52 remission acute leukemia patients, there was no association between minimal residual disease (MRD) and 3-year PFS: MRD negative of 88% vs MRD positive of 77% (P = 0.375).
Conclusions: Intermediate intensity dCBT is associated with high PFS. Use of highly HLA mismatched and unmanipulated grafts permits wide application of this therapy, and the low relapse rates support robust graft-versus-leukemia effects even in patients with MRD.

Optimizing Selection of Double Cord Blood Units for Transplantation of Adult Patients with Malignant Diseases

Fatobene G et al, Blood Advances, 2020
Eurocord, Paris, France

Current guidelines on unrelated cord blood (UCB) unit selection are mainly based on single-unit UCB data.
Methods: A total of 1375 adult recipients of DUCBT for hematologic malignancies were retrospectively analyzed to determine optimal criteria for graft selection for double-unit unrelated cord blood transplantation (DUCBT).
Findings: Cryopreserved CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved overall survival. Low total nucleated cell (TNC) (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/kg) cell doses were related to decreased neutrophil recovery. DUCBT recipients with ≥2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease.
Conclusions: The data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.

Impact of T-cell Repertoire Diversity on Mortality following Cord Blood Transplantation

Milano F et al, Frontiers in Oncology, 2020
Fred Hutchinson Cancer Research Center, USA

There are no data on the association of T-cell receptor (TCR) and clinical outcomes after cord blood transplantation (CBT).
Methods: Peripheral blood (PB) samples of 34 CBT patients was collected for retrospective analysis of immune recovery utilizing high-throughput sequencing of TCRβ rearrangements from genomic DNA extracted from PB mononuclear cells.
Results: Rapid turnover of T-cell clones was observed at each time point, with TCR repertoires stabilizing by 1-year posttransplant. TCR diversity values at day 100 for patients who died between 100 and 365 days posttransplant were significantly lower than those of the surviving patients (p = 0.01).
Conclusions: Using a fast high-throughput TCR sequencing assay, the study demonstrated that high TCR diversity is associated with better patient outcomes following CBT. Importantly, this assay is easily performed on posttransplant PB samples, even as early as day 28 posttransplant, making it an excellent candidate for early identification of patients at high risk of death.

Updated Comparison of 7/8 HLA Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Umbilical Cord Blood Transplantation as Alternative Donors in Adults with Acute Lukemia

Miyao K et al, Biology of Blood and Marrow Transplantation, 2020
Anjo Kosei Hospital, Japan

The outcomes of 7/8 allele-matched unrelated bone marrow transplantation (7/8 UBMT) and umbilical cord blood transplantation (UCBT) have been improving.
Methods: Adults with acute leukemia who underwent their first 7/8 UBMT or UCBT in Japan were analyzed.
Results: Overall survival at 3 years was 54% for 7/8 the UBMT group and 46% for the UCBT group, a nonsignificant difference in multivariate analysis. The 7/8 UBMT and UCBT groups showed a similar non-relapse mortality rate and relapse rate. However, the UCBT group had a lower risk of grade II-IV acute GVHD (HR, 0.76; 95% CI, 0.65 to 0.88; P < .001) and chronic GVHD (HR, 0.77; 95% CI, 0.66- 0.91; P = 0.002) compared with the 7/8 UBMT group.
Conclusions: Both 7/8 UBMT and UCBT are appropriate alternative donor procedures.

Double Unrelated Umbilical Cord Blood versus HLA-Haploidentical Bone Marrow Transplantation (BMT CTN 1101)

Fuchs E et al, Blood, 2020
Sidney Kimmel Cancer Center at Johns Hopkins University, USA

Two parallel Phase II trials of transplantation of unrelated umbilical cord blood and bone marrow from HLA-haploidentical relatives provided equipoise for direct comparison of the donor sources.
Methods: Between June 2012 and June 2018, 368 patients aged 18-70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo cord blood (n=186) or haploidentical (n=182) transplant.
Results: Two-year progression-free survival was 35% compared to 41% after cord blood and haploidentical transplants, respectively (p=0.41). Pre-specified analysis of secondary endpoints recorded higher 2-year non-relapse mortality after cord blood, 18% compared to haploidentical transplantation, 11%, p=0.04. This led to lower 2-year overall survival after cord blood compared to haploidentical transplantation, 46% and 57%, respectively (p=0.04).
Conclusion: The trial did not demonstrate a statistically significant difference in the primary endpoint, 2-year progression-free survival, between the donor sources. While both donor sources extend access to reduced intensity transplantation, analyses of secondary endpoints, including overall survival, favor haploidentical bone marrow donors.

Umbilical Cord Blood-Derived ILC1-like Cells Constitute a Novel Precursor for Mature KIR+NKG2A- NK Cells

SB Bennstein et al, eLife, 2020  
Heinrich-Heine University Düsseldorf, Germany

The study aimed at dissecting the developmental relationship between human ILC1 and NK cells in umbilical cord blood (CB).
Methods: CB ILC1 and both NK cell subsets (CD56dim and CD56bright NK cells) were sorted for transcriptomic comparison via RNA sequencing. The developmental potential of CB ILC1 was explored by single cell cloning and in vitro differentiation assays.
Findings:  The study demonstrates that neonatal ILC1-like cells are very different from NK cells on the transcriptional, epigenetic, and functional level but instead constitute a potent NK cell precursor (NKP). The ILC1-like NKP is distinguished from previously defined NKPs and ILCPs by the absence of CD117, the presence of T cell-specific molecules such as CD5 and CD6, and the property to generate diversified NK cell repertoires characterized by KIR expression as well as the downregulation of NKG2A.
Conclusion: Based on this data, a branched model of NK cell development is proposed, where where CB ILC1-like cells as well as CD56bright NK cells both harbor NKP potential and contribute to the diverse phenotypes seen in CD56dim NK cell in vivo.

GMP-Grade CD34
+Selection from HLA-Homozygous Licensed Cord Blood Units and Short-Term Expansion under European ATMP Regulations

Liedtke S et al, Vox Sang, 2020
University Clinic, Düsseldorf

Based on a synergistic consortium, the Düsseldorf cord blood bank Düsseldorf was responsible for the selection of HLA-homozygous donors (HLA-h), re-consenting the mothers, GMP-grade CD34+ enrichment, followed by short term expansion of CD34+ cells and qualification as advanced therapy medicinal product.
Methods: Among 20,639 licensed cord blood units (CBUs), 139 potential donors were identified with the most frequent 10 German haplotypes and, for 47.5%, consent was obtained. Thawing/washing of CBUs was performed in the presence of Volulyte/HSA with Sepax, CD34+ selection by automated GMP-grade CliniMACS-system, expansion with qualified GMP-grade cytokines in the GMP-facility.
Findings: The investigators confirmed that n=10 CB units with a maximal storage time of 16 years with >80% CD34+ purity and > 70%viability after CD34+ selection could be expanded until day 3/4 to a mean purity of 86.0 +10.38% and a viability of 96.07+4.72% and provided for reprogramming.
Conclusions: Approval by the local government was obtained for this product as a starting material under European ATMP regulations as a requirement for clinical translation and implementation of a qualified manufacturing process. This approach considers the main obstacle of rejection of transplanted cells by preselection of HLA-homozygous transplants.

Effect of Graft-versus-Host Disease on Outcomes after Pediatric Single Cord Blood Transplantation

Kanda J et al, Bone Marrow Transplantation, 2020
Kyoto University, Japan

The effect of GVHD on transplant outcomes after unrelated cord blood transplantation (UCBT) is not yet fully understood.
Methods: Pediatric patients aged 0-15 years with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n = 740) were selected from the Japanese registry.
Findings: The occurrence of grade III-IV acute GVHD was associated with a higher risk of non-relapse mortality compared with no acute GVHD. Grade I-II acute GVHD was not associated with non-relapse mortality. The occurrence of grade I-II or grade III-IV acute GVHD was not associated with a relapse risk. The occurrence of limited chronic GVHD was associated with a low risk of overall mortality.
Conclusions: Severe acute GVHD should be prevented because of its association with high overall mortality and non-relapse mortality in pediatric single UCBT. Mild acute GVHD provides no overall benefit. Mild chronic GVHD may be beneficial for survival.


Adult Cord Blood Transplant Results in Comparable Overall Survival and Improved GRFS vs Matched Related Transplant

Sharma P et al, Blood Advances, 2020
University of Colorado, USA

Methods: Outcomes among adult matched related donor (MRD) patients undergoing peripheral blood stem cell transplantation and adult patients undergoing double unit CBT were compared.
Findings: A total of 190 CBT patients were compared with 123 MRD patients. Comparing all CBT with all MRD patients, overall survival (OS) was comparable and GVHD relapse-free survival (GRFS) was significantly improved among CBT patients. Among patients undergoing most commonly used MRD and CB myeloablative regimens, OS was comparable and GRFS was significantly improved among CBT patients. Cumulative incidence of relapse trended toward decreased in the CBT group, whereas transplant-related mortality was comparable.
Conclusions: Among patients able to tolerate more intensive conditioning regimens at high risk for relapse, CB may be the preferred donor source.

Splenomegaly Negatively Impacts Neutrophil Engraftment in Cord Blood Transplantation

Yuasa M et al, Biology of Blood and Marrow Transplantation, 2020
Toranomon Hospital, Japan

Splenomegaly exerts negative effects on neutrophil engraftment, but the appropriate cell dose for the patients with splenomegaly has not yet been determined, especially in CBT.
Methods: We retrospectively investigated the effect of splenomegaly and number of CD34+ cells infused on neutrophil engraftment through the analysis of outcomes of 502 consecutive patients who underwent single CBT for the first time at Toranomon Hospital between 2011 and 2018.
Findings: Splenomegaly and low dose of infused CD34+ cells had significant negative impact on neutrophil engraftment, whereas neither CFU-GM dose nor TNC dose had any impact on neutrophil engraftment in multivariate analysis. Without splenomegaly, even patients infused with <0.8 × 105/kg CD34+ cells achieved up to 94.3% neutrophil engraftment, with the median value observed at 21 days post-CBT.
Conclusions: This study shows that aplenomegaly has a significant negative impact on neutrophil engraftment after CBT. Cord blood units with <0.8× 105/kg CD34+ cells may still be a suitable choice for patients without splenomegaly.

Optimal Donor for African Americans with Hematologic Malignancy: HLA-Haploidentical Relative or Umbilical Cord Blood Transplant

Solomon SR et al, Biology of Blood and Marrow Transplantation, 2020
Northside Hospital, USA

As only about 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation.
Methods: The current analyses studied transplant-outcomes after HLA-haploidentical relative (n=249) and umbilical cord blood (n=118) transplants for African Americans with hematologic malignancy between 2008 and 2016.
Findings: Grade II-IV and III-IV acute GVHD was higher after umbilical cord blood (56% and 29%, respectively) compared to HLA-haploidentical relative transplantation (33% and 11%). The 2-year incidence of transplant-related mortality adjusted for age and conditioning regimen intensity was higher after umbilical cord blood compared to HLA-haploidentical relative transplantation (31% versus 18%, p=0.008). However, there were no differences in the 2-year adjusted incidence of relapse (30% versus 34%, p=0.51), overall survival (54% versus 57%, p=0.66), or disease-free survival (43% versus 47%, p=0.46).
Conclusions: HLA-haploidentical and umbilical cord blood extend access to transplantation with comparable leukemia-free and overall survival for African Americans with hematologic malignancy.

Prognostic Factors for Adult Single Cord Blood Transplantation among European and Japanese Populations: the Eurocord/ALWP-EBMT and JSHCT/JDCHCT Collaborative Study

Kanda J et al, Leukemia, 2020
Kyoto University, Japan

Large differences in patient and transplant backgrounds make it difficult to identify consistent prognostic factors of unrelated cord blood transplantation (UCBT) among different populations.
Methods: Adults with acute leukemia who underwent a single UCBT were eligible. In total, 3764 and 1027 patients of the JSHCT/JDCHCT and Eurocord/ALWP-EBMT registries, respectively, were included.
Findings: The median total nucleated cell (TNC) counts were 2.58 and 3.51 × 10*7/kg in the Japanese and European cohorts, respectively. Anti-thymocyte globulin was used in only 2% of the Japanese cohort compared with 65% of the European cohort. In the multivariate analysis, TNC dose and HLA matching had no significant effect on overall survival in either cohort, whereas transplant year, age, and disease risk affected overall survival in both cohorts.
Conclusion: Despite considerable differences in characteristics between the Japanese and European cohorts, similar prognostic factors affecting UCBT outcomes were identified.

Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors

Liu E et al, New England Journal of Medicine, 2020
M.D. Anderson Cancer Center, USA

In this phase 1 - 2 trial, 11 patients with relapsed/refractory CD19+ malignancies received HLA-mismatched anti-CD19 CAR-NK cells derived from umbilical cord blood units.
Methods: NK cells were isolated and transduced with a retroviral vector expressing genes that encode anti-CD19 CAR. Furthermore, they were also transduced with interleukin-15 to improve survival and long-term persistence, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy.
Findings: No cytokine release syndrome, neurotoxicity and graft versus host disease were documented. The maximum tolerated dose was not reached. 73% (8/11) had a clinical response. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months.
Conclusion: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects.

Successful Umbilical Cord Blood Transplantation in Children with Leukocyte Adhesion Deficiency Type I

Qian X et al, Translational Pediatrics, 2020
Children’s Hospital of Fudan University, Shanghai

This study aims to investigate the efficacy and safety of cord blood transplantation (CBT) without serotherapy for treating children with leukocyte adhesion deficiency type I (LAD-I).
Methods: Five patients with LAD-I received CBT with myeloablative, busulfan-based conditioning, at a median age of 9 months.
Findings: Neutrophil and platelet engraftment were achieved after 20 (r 13-28) and 36 days (r 32-56) respectively, all 5 achieved full donor chimerism. Two patients developed grade III-IV GvHD. After a median follow up of 19 months, 4 out of 5 patients were alive and well.
Conclusion: Umbilical cord blood transplantation is an effective treatment method for LAD-I patients. Also, severe LAD-I patients should undergo stem cell transplantation as early as possible.

Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

Suzdaltseva Y et al, Stem Cells International, 2020
Vavilov Institute of General Genetics, Russia

In this randomized, placebo-controlled study, the authors investigated the ability of umbilical cord derived mesenchymal stromal cells (MSCs) to regulate chronic inflammation in patients with nonhealing wounds.
Methods: 108 patients with chronic wounds of different etiologies were enrolled: study group (n=59) received a single local subcutaneous infusion of UC-derived MSCs around the wound, whereas control group (n=49) received placebo.
Findings: The study group showed marked growth of granulation tissue, improved blood microcirculation, and reduction in wound size compared to the placebo group; complete wound resolution was achieved in 22% in the study group and 8.2% in the placebo group.
Conclusion: Locally delivered allogeneic umbilical cord MSCs can contribute to chronic wound repair and provide an additional support toward new therapeutic strategies.

Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Treating Chronic Obstructive Pulmonary Disease: a Pilot Clinical Study

Bich P et al, Stem Cell Research and Therapy, 2020
Van Hanh General Hospital, Viet Nam

This study investigated the safety and efficacy of umbilical cord-derived (UC)- mesenchymal stem cells (MSCs) for treating chronic obstructive pulmonary disease (COPD).
Methods: Twenty patients were included, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients received 10cells/kg of expanded allogeneic UC-MSCs.
Findings: No infusion-related toxicities or severe adverse events were documented. At a 6-month evaluation, patients showed significant improvement of several outcomes of COPD and reduced the number of exacerbations, likely due to downregulated inflammation.
Conclusion: Systemic UC-derived MSCs administration were safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations.

Therapeutic Evidence of Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Cerebral Palsy: a Randomized, Controlled Trial

Gu J et al, Stem Cell Research and Therapy, 2020
First Affiliated Hospital of Xi’an Jiaotong University, People’s Republic of China

This randomized, placebo-controlled study aimed to evaluate the safety and efficacy of UC-derived MSC transplantation concomitant with rehabilitation in patients with cerebral palsy.
Methods: In addition to rehabilitation, patients in the study group (n=20) received four transfusions of UC-derived MSCs intravenously, while the control group (n=20) received placebo.
Findings: The study showed that hUC-MSC transplantation was safe and feasible and was not related to higher incidence of adverse events. Furthermore, the study group showed a significant improvement in activities of daily living, comprehensive function assessment and gross motor function measure. Five patients from the study group and 8 from the control group received PET/CT scan as optional assessment to explore cerebral glucose metabolism; 0/8 cases from the control group and 3/5 cases from the study group showed an increase in the SUV at 1 year evaluation.
Conclusion: Recovery of cerebral metabolic activity might play an essential role in brain function improvement in patients with cerebral palsy.

High Incidence of Acute Kidney Injury after Cord Blood Transplant

E Xue et al, Biology of Blood and Marrow Transplantation, 2020
Fred Hutchinson Cancer Research Center, USA

In this retrospective study, the authors aimed to identify incidence and risk factors of acute kidney injury (AKI) in 276 patients who received CBT for hematologic malignancies and to evaluate the impact of AKI on transplant outcome.
Methods: AKI was staged using the Kidney Disease Improving Global Outcomes (KDIGO) system (stages 1-3). Most (88%) patients received myeloablative conditioning regimen, including high dose total body irradiation. 41%, 16% and 11% patients developed a maximum of stage 1, stage 2 and stage 3 AKI, respectively.
Findings: As expected, stage 2-3 AKI was associated with higher 1-year NRM and decreased overall survival. In MV analysis, bilirubin level was significantly associated with AK.
Conclusion: The use of steroids was associated with lower risk of developing AKI. The protective effect exerted by steroids is of clinical interest and warrants further investigation.

Hematopoietic Stem Cell Transplantation Using Single UM171-Expanded Cord Blood: a Single-Arm, Phase 1-2 Safety and Feasibility Study

Cohen S et al, Lancet Haematology, 2020
Maisonneuve-Rosemont Hospital, Canada

Authors investigated the safety and feasibility of single UM171-expanded cord blood transplantation in patients with hematological malignancies who do not have a suitable HLA-matched donor.
Methods: Patients were infused with the 7-day UM171-expanded CD34-positive cells and the lymphocyte-containing CD34-negative fraction.
Findings: Among the 22 patients who received single UM171-expanded cord blood transplantation, median time to engraftment of 100 neutrophils per μL was 9·5 days (IQR 8-12), median time to engraftment of 500 neutrophils per μL was 18 days (12·5-20·0), and no graft failure occurred.
Conclusion: UM171 cord blood stem cell expansion is feasible, safe, and allows for the use of small single cords without compromising engraftment.



Effect of Single or Double Mismatches at Each HLA Locus on the Outcomes after Single Cord Blood Transplantation: The JSHCT HLA WG Study

Junya Kanda et al, Kyoto University, Japan

This analysis identifies the effect of HLA locus mismatches on CBT outcome.

Methods:  4074 adults who received a first CBT between 2003 and 2017 were included. The impact of HLA mismatches was analysed after adjusting for other variables.
Results:  There was no impact of specific HLA locus mismatches on overall survival. Both single and double -B and double -DRB1 mismatches were associated with higher non-relapse mortality, whereas, double -A and -DRB1 mismatches and single -B mismatch were associated with a lower relapse risk. Higher risk of II-IV and III-IV acute GVHD was seen with either single or double HLA-DRB1 mismatches; single mismatch at the -A and -B loci also were associated with III-IV acute GVHD.
Conclusion:  Given the association of double -DRB1 mismatch with higher II-IV and III-IV GVHD, higher NRM and lower relapse risk, the authors concluded that not only locus mismatch but also the number of mismatches at the DRB1 locus should be considered in CBU selection.

An “All in One” T-cell Product from Non-Transplantable Cord Blood Units for Virus- and Leukemia-Specific T-cell Immunotherapy

Kyriakos Koukoulias et al, George Papanicolaou Hospital, Greece

The authors aimed to generate an “all-in-one” T-cell product with both AML antigen- and virus antigen- specific T-cells (LEVIS) starting from non-transplantable umbilical cord blood units.

Methods:  Matured CD34+-derived dendritic cells from CBU were stimulated with both leukemic (WT1 and PRAME antigen) and viral (from EBV, CMV, AdV and BKV) peptide mixes and used to “educate” naïve T-cells.
Results:  The resultant LEVIS products contain both CD4+ and CD8+ polyclonal population, expressing effector memory markers, with low amount of naïve and regulatory T-cells. LEVIS demonstrated low expression levels of PD-1 and of CTLA-4. Also, LEVIS showed high specificity against all targeted antigens suggesting successful T cell “training” and lack of antigen competition.
Conclusion:  Non-transplantable CBUs might represent the future for third-party, “off-the-shelf” immunotherapy tool for improving the outcome of allogeneic transplants.

The Use of Post-Transplant Cyclophosphamide (PT-Cy) in Unrelated Umbilical Cord Blood Transplantation

Patrizia Chiusolo et al, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Italy

The use of anti-thymocyte globulin makes immune recovery slow in CBT setting. The authors aimed to substitute it with high-dose post-transplant cyclophosphamide (PT-CY) and analyze its effect on CBT outcome. 

Methods:  Ten adults diagnosed with acute leukaemia or myelodysplasia were enrolled. Conditioning regimen was TBF (Thiotepa, Busulfan, Fludarabine) and PT-CY 30 mg/kg on days+3&+5; patients received cyclosporine and mycophenolate mofetil. The median nucleated cell dose was 3.1x107/kg.
Results:   Median time to ANC > 0.5x109/l and PLT > 20x109/l was day 23 days (range 17-27) and 38 days (range 34-40), respectively. Two patients failed to engraft. The median CD4+ count on day +100 was 111/uL (range 100-136). CMV requiring treatment occurred in 3/6 evaluable patients. After a median follow up of 231 days, seven patients are alive and well; two patients died early of infections. None required treatment for acute/chronic GVHD, and none relapsed.
Conclusion:  The use of PT-CY in CBT feasible and leads to encouraging hematologic and immunologic recovery.


SELECTED ABSTRACTS:  2020 Cord Blood Connect International Congress

Targeting Neuroinflammation with Human Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells

Min H et al, Duke University, USA

Mesenchymal stromal cells (MSCs) are a form of cellular therapy that reduces inflammation. Inflammation is common in many neurologic diseases, such as multiple sclerosis.  Umbilical cord tissue-derived MSCs were used in a mouse model of demyelinating neurologic disease.

Methods:  Umbilical cord tissue-derived MSCs lines were prepared from donated cord tissue from healthy, term, c-section deliveries, under GMP conditions. To monitor physical interactions between cells, the authors stained hCT-MSCs with cell tracking dyes and then assessed the response of monocytes and macrophages (immune system cells) by RNA sequencing and functional T cell suppression assays. Control and genetically manipulated umbilical cord tissue-derived  cells were studied in a mouse model of demyelination.
Results:  Macrophages engulfed cytoplasmic components of umbilical cord blood-derived MSCs and  suppressed T cells.  The cells enhanced remyelination in the spinal cord after induced demyelination.
Conclusion:  The authors determined that hCT-MSCs program macrophages to suppress T cells and enhance remyelination of the spinal cord.  These cells can alter the immune response and may be beneficial for the treatment of neurologic diseases.


Single UM171-Expanded Cord Blood Transplants Support Robust T-Cell Reconstitution with Low Rates of Severe Infections

Dumon-Lagace M et al, ExCellThera Inc., Hôpital Maisonneuve-Rosemont, Montréal, Quebec, Canada

Rapid T cell (immune system) recovery following stem cell transplantation is essential for protection against infections and has been associated with improved survival. Umbilical cord blood (UCB) transplants are associated with lower rates of chronic graft vs host disease and relapse, but the slower immune recovery leads to a higher risk of infections. Results of a smaller phase I/II trial revealed that a single expanded CB transplant allowed the use of smaller CB units without compromising engraftment.

Methods:  The authors performed a retrospective analysis of a cohort of 20 patients treated with UM171-expanded CB and compared it to a contemporary cohort of 12 patients treated in the same institution who received unmanipulated CB transplant with similar conditioning regimens.
Results:  The median T cell dose in the expanded graft was at least 2 to 3 times lower, but the phenotype of T cells at 3, 6, and 12 months post-transplant were similar between the two cohorts. T cell receptor sequencing analyses revealed that UM171 patients had greater T cell diversity at 12 months post-transplant. UM171 patients showed a significantly reduced incidence of severe infections, especially for bacterial and viral infections.
Conclusions:  These results suggest that patients receiving UM171 expanded cord blood units benefit from rapid T cell reconstitution, and have fewer infections.


SELECTED ABSTRACTS:  2019 American Society of Hematology Annual Meeting

Outcomes of Chronic Graft-Versus-Host Disease following Matched Sibling Donor versus Umbilical Cord Blood Transplant

Okoev G et al, University of Minnesota, USA

Single center retrospective study of 104 patients receiving matched sibling donor (MSD) and 41 patients receiving umbilical cord blood transplantation (UCBT).

Findings:  Severe chronic graft-versus-host disease (cGVHD) was more common following MSD transplantation.  Liver GVHD was more common in MSD peripheral blood stem cell transplant (PBSCT), whereas GI involvement was significantly more frequent in UCBT.  There was no difference in treatment response to cGVHD between MSD and UCBT.
Conclusion:  The treatment response to cGVHD was the same for recipients of matched sibling donor and umbilical cord blood transplantation.

Romiplostim Improves Platelet Recovery after Umbilical Cord Blood Transplant

Christakopoulos C et al,  University of Minnesota, USA

Single center dose-escalation study of romiplostim for patients who failed to achieve platelet recovery by day +28 following umbilical cord blood transplantation (UCBT).  21 patients were enrolled.
Findings:  All patients treated with romiplostim achieved platelet engraftment (>20 x 109/L) by day +45.  The maximum tolerated dose was determined to be 10mcg/kg/d.
Conclusions:  Romiplostim appears safe and well tolerated for management of delayed platelet recovery following UCBT.  Larger, confirmatory studies are justified.

Comparison of Outcomes between Hematopoietic Stem Cell Transplant Donor Sources for Pediatric Patients with Hematologic Malignancies

Longo L et al,  Fred Hutchinson Cancer Research Center, USA

Retrospective analysis of the outcomes of 232 pediatric hematopoietic stem cell transplant recipients with 56 matched sibling donors, 89 matched unrelated donors, and 87 umbilical cord blood donors.
Findings:  There was no difference in 5-year unadjusted overall survival or non-relapse mortality between the groups.  The risk of disease relapse was significantly lower for recipients of umbilical cord blood grafts.
Conclusion:  This study is consistent with a previously reported study of adult patients from the same research center, suggesting a potent graft-versus-tumor response from the umbilical cord blood graft.

High Incidence of Herpes Zoster after Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis

Xue E et al, Fred Hutchinson Cancer Research Center, USA

Retrospective assessment of the incidence of herpes zoster after umbilical cord blood transplantation (UCBT).
Findings:  The cumulative incidence of herpes zoster following UCBT was 1.8% at 1 year,  and 26% at 5 years.  Disseminated herpes zoster occurred in 5 cases (11%), and post-herpetic neuralgia occurred in 14 cases (31.8%).
Conclusion:  Herpes zoster occurs commonly after UBCT, particularly once herpes zoster prophylaxis is discontinued.  Until an effective vaccine strategy emerges, UBCT recipients should remain on long-term zoster prophylactic medications.

Unrelated Cord Blood Transplantation and Post-Transplant Cyclophosphamide

Chiusolo P et al, Universitario Agostino Gemelli, Italy

Pilot study to test feasibility of post-transplantation cyclophosphamide (PT-CY) as a graft-versus-host disease (GVHD) prophylaxis for recipients of umbilical cord blood transplantation (UCBT).
Findings:  10 patients received myeloablative conditioning with thiotepa (10 mg/kg), busulfan (9.6 mg/kg) and fludarabine (150 mg/m) (TBF). GVHD prophylaxis was cyclosporin, myophenolate mofetil and PT-CY (30 mg/kg days +3 and +5).   Of the 8 patients evaluable for engraftment, one patient experienced graft failure.  Mild acute GVHD was observed in 1 patient.
Conclusion:  Post-transplant cyclophosphamide following UCBT appears feasible.  More experience is needed to assess the risk of graft failure and the delay in hematopoietic recovery.