Highlights from 2017

Below are highlights from the 15th International Cord Blood Symposium.

Improving Cord Blood Transplantation Outcomes


Session Featured Recent Data on Methods to Improve UCB
Transplantation Outcomes

Omar Aljitawi, MD

Presenters at Thursday's session on improving outcomes of umbilical cord blood (UCB) transplantation at the 15th International Cord Blood Symposium (ICBS) will discuss promising methods to improve expansion, homing and engrafting will feature a session on innovative models for cord blood banking. Session Chair, Omar Aljitawi, MD, will kick the session off with a discussion of recent findings on the use of hyperbaric oxygen (HBO) therapy to improve UBC stem/progenitor cell homing and engraftment. Aljitawi is an associate of hematology/oncology at the University of Rochester Medical Center in New York.

In a study recently published in "Blood,” Aljitawi and colleagues demonstrated the safety and feasibility of HBO therapy to improve homing and engraftment of cord blood-derived hematopoietic stem/progenitor cell (HSPCs) in bone marrow.1 "We've shown that you can use hyperbaric conditions as a way to do that. And we've shown that it's feasible, and based on comparison with our historic data we've seen favorable recovery of our patients,” he said in an interview.

UCB transplant in adults can be limited by low cell doses, which can result in delayed engraftment and engraftment failure. In addition, UCB stem/progenitor cell homing to the bone is not efficient. Delayed engraftment puts patients at risk for infection and other complications. Two options to improve engraftment are under exploration to improve. One option is to enhance expansion of cells in vitro using growth factors and chemokine stimulators. The other approach is to improve the homing of UCB stem cells in vivo.

Aljitawi became interested in the second approach after reading a paper describing a correlation between the plasma concentration of the hormone erythropoietin (EPO) in neonates and the declining kinetics of hematopoietic progenitor cells (HPCs) shortly after birth.2 This suggested an inverse relationship for EPO signaling in HSPC bone marrow homing. HBO therapy has been demonstrated to lower EPO levels in healthy volunteers, leading Aljitawi to hypothesize that HBO therapy could improve homing in UCB transplant patients via reduced EPO levels.

Using animal models, the researchers demonstrated that exposure of HSPCs to EPO-receptor inhibited migration and enhanced erythroid differentiation (EPO is known to "push” HPCs to favor erythroid differentiation). However, reducing the expression of EPO receptor on HSPCs through HBO treatment promoted homing and myeloid differentiation.

Following these results, Aljitawi and colleagues undertook a pilot study to assess and measures of efficacy of standard HBO therapy within six hours of transplantation of UCB CD34+ HSPCs to blood in 15 patients with acute myeloid leukemia, non-Hodgkin lymphoma or acute lymphoblastic leukemia.

All patients completed HBO therapy — except for one patient who stopped the treatment 10 minutes early due to nausea. Few unexpected complications were reported and it was unclear if those were related to HBO. As expected, some or all patients experienced leukopenia (grade IV), neutropenia and anemia (grade III/IV) and thrombocytopenia (grade III/IV). Compared with matched historic controls, patients who underwent HBO therapy had improved neutrophil and platelet recovery and survival at 100 days post-transplant.

The session will also include presentations by Guy Sauvageau, MD, and Filippo Milano, MD, PhD. Sauvageau, who is the founder of the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal and holds the Canada Research Chair in the Molecular Genetics of Stem Cell, will discuss the use of pyrimidoindole derivative UM171 for cord blood expansion. Milano, who is the associate director of the Cord Blood Program at Fred Hutchinson Cancer Research Center and an assistant professor at the University of Washington in Seattle, will address cord blood transplantation in patients with minimal residual disease.

1Aljitawi OS, Paul S, Ganguly A, et al. Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation. Blood. 2016;128:3000-10.
2Gonzalez S, Amat L, AzquetaC, et al. Factors modulating circulation of hematopoietic progenitor cells in cord blood and neonates. Cytotherapy. 2009;11:35-42.

Innovative Models for Cord Blood Banking


Session Included Snapshot of Perinatal Cell Trials

Frances Verter, PhD

The 15th International Cord Blood Symposium (ICBS) will feature a session on innovative models for cord blood banking. Moderated by Frances Verter, PhD, the founder and director of the Parent's Guide to Cord Blood Foundation, the session will highlight industry trends, collaborative cord blood (CB) banking and therapy with cells derived from perinatal tissues.

Verter will kick the session off with a discussion of industry data from a soon-to-be-published paper that is an outgrowth of the launch of the CellTrials.org website. The website collects information about advanced cell therapy trials and cell therapy products and sells the raw data from its database.

Drawing from this database, Verter investigated the first decade of advanced cell therapy clinical trials using perinatal cells, along with coauthors Pedro Silva Couto, MSc, also from the Parent's Guide to Cord Blood, and Alexey Bersenev, MD, PhD, director of Advanced Cell Therapy/ Cell Processing Labs at Yale-New Haven Hospital. While the CellTrials database covers the years 2011 and after, they extended their search for perinatal trials back to 2005 for a decadal analysis.

A total of 278 advanced cell therapy clinical trials using perinatal cells from 2005 to 2015 were included in the study. To qualify as advanced cell therapy, the trials had to use perinatal cells in a manner that was either non-homologous or that manipulated the cells. Conventional oncology clinical trials were not included. The trials were analyzed using 15 parameters.

Verter and colleagues found that researchers in different countries tend to prefer different cell sources or cell types. China dominates the field of cord tissue research, accounting for 78 percent of trials. However, most of the world's advanced cell therapy trials with cells from cord blood are in the United States and South Korea, which collectively account for 69 percent of the trials in the study, according to the researchers. The United States also accounts for more than half of trials using perinatal cells from other sources (54 percent).

The findings highlight different perinatal-cell research paradigms in China, the United States and South Korea, said Verter. The predominance of China in cord tissue research may reflect substantial national regulation for cord blood banking but not for the Wharton's Jelly in cord tissue. The United States has a long history of CB banking that provides momentum for CB trials. In South Korea, the use of CB from unrelated donors is less regulated. This accounts for the rapid growth of the CB field in South Korea, despite its later entry to CB trials.

Hematopoietic stem cells (HSC) from CB have been used for stem cell transplants since 1988. However, it wasn't until 2005 that CB was first used as a regenerative medicine, with Joanne Kurtzberg, MD, at Duke University performing autologous CB transplants for children with acquired neurological disorders.

That work launched the field of perinatal cell-based advanced cell therapy. Since then, interest has shifted from HSCs to mesenchymal stem cells (MSC) from perinatal sources. Perinatal-cell MSC trials have grown much faster than trials with HSC from cord blood, Verter said. The next growth surge in trials is predicted to be epithelial stem cells (EpSC) that can be found in the amniotic membrane of the placenta.

The Friday session will also include presentations by Vinesh Arvind Mandot and Tomasz Baran, MD, MBA. Mandot, who is the technical lead at LifeCell International Private Limited in Chennai, India, will discuss a community pool model of collaborative CB banking in India. Baran, of PBKM/FamiCord Group in Warsaw, Poland, will address the use of Wharton's jelly-derived MSCs for graft-versus-host disease and other indications.