Newsletter - August 2015

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Interview with Kyle Cetrulo about the Perinatal Stem Cell Society

Kyle Cetrulo, co-founder Perinatal Stem Cell Society

Kyle Cetrulo, CEO of AuxoCell & co-founder of the Perinatal Stem Cell Society

Where and when is the Perinatal Stem Cell Society Conference?

The 2nd annual Perinatal Stem Cell Society Conference is taking place March 2-4, 2016 in Aspen CO, USA. The conference venue is the Aspen Meadows Resort, a world-class resort and conference center.

What is the story behind the Perinatal Stem Cell Society?

We decided to start the Perinatal Stem Cell Society (PSCS) after we edited the book, Perinatal Stem Cells, Second Edition. We wanted to continue the momentum of the book and create a society where like-minded individuals could meet and collaborate to advance the perinatal stem cell field towards the clinic. Our goals for the society are embodied in our slogan: "Advancing perinatal stem cell research on the path toward treatment".

Membership in the Perinatal Stem Cell Society is FREE so I encourage everyone who is interested in perinatal stem cells to join the society, even if unable to attend the conference this year. Each registrant for the conference will receive a free download of the entire book "Perinatal Stem Cells, Second Edition".

Perinatal Stem Cell Society

Who should attend the Perinatal Stem Cell Society conference?

The conference is designed to help cord blood bankers learn about perinatal stem cells as well as to create a space for collaboration. Our goal is to utilize the Perinatal Stem Cell Society to educate the cord blood industry on how to process the highest quality cord tissue, amnion, and placenta derived products.

What is the program for the upcoming meeting?

We're hosting an incredible scientific program with topics covering all aspects of the perinatal stem cell field. The faculty line-up for this 3-day event will feature the world's leading perinatal stem cell researchers, specializing in Amnion, Amniotic fluid, Cord Blood, Cord Tissue, and the Placenta. We consciously worked to include both veteran speakers in the field as well as newer researchers who are also doing amazing work. I think this approach keeps the subject matter fresh, which is the whole point of the meeting.

Day 1: Wednesday March 2nd

The conference kicks off Wed. evening with an Après Ski Style reception followed by a great dinner and a keynote presentation by C. Randal Mills, PhD, CEO of the California Institute of Regenerative Medicine (CIRM). Dr. Mills is a reknowned speaker who can share his experiences bringing the first approved stem cell product to market during his tenure at Osiris, followed by his experience guiding CIRM.

Day 2: Thursday March 3rd

Thursday is a full day's program. The day starts with Joanne Kurtzberg, MD, of Duke University Medical Center and Charles S. Cox, Jr. MD, of the University of Texas Health Science Center sharing their experiences treating pediatric brain injuries with cord blood. Hopefully they will have some fresh data from their paradigm-shifting clinical trials.

Talks focused on the placenta will be given by Robert Hariri, MD, PhD, of Celgene Cellular Therapeutics as well as Graham Jenkins, PhD, and Richard Boyd, PhD, from Monash University in Australia.

Talks on amnion stem cells will be presented by Ornella Parilini, PhD, the President of IPLASS, Aleksander Skardal, PhD, from Wake Forest, Euan Wallace, MD, from Monash University, and others. Hopefully Stephen Strom, PhD, from the Karolinski Institute will have first-in-human results from a trial using amnion epithelial stem cells to treat liver disease.

Thursday evening we're hosting a Sports Medicine Program that is open to the public and will be advertised throughout Aspen. Dr. Dennis Lox, a renowned Sports Medicine Surgeon, will moderate the program and we have an outstanding panel of leaders in the sports medicine field. The panel is highlighted by Mikel Sánchez Álvarez, MD, who performed plasma rich therapy on tennis champion Rafael Nadal.

Day 3: Friday March 4th

Friday is a half-day program dedicated exclusively to discussing cord tissue derived stem cells and their potential therapeutic uses. Kang-Hsi Wu, MD, of China Medical University Hospital, will present first-in-human results using MSC from cord tissue to enhance cord blood transplants.

We've allotted ample time to discuss current cord tissue processing methods. We'll examine the philosophies of storing native stems cells that are ready for transplant or expanding stem cells from the cord tissue. We'll consider where each of these processing methods have advantages and disadvantages for potential therapies.

Where will this conference lead?

This conference should be exciting for anyone who is interested in stem cell based regenerative medicine. Perinatal stem cells have huge potential to help patients in need. For researchers, our goal is to use the Perinatal Stem Cell Society to educate and create a platform for collaboration in order to "Advance perinatal stem cell research on the path toward treatment".

Kyle Cetrulo brings 15 years of experience in the stem cell industry to his position as chief executive officer of Auxocell. Kyle Cetrulo has been promoting Perinatal Stem Cells since 1998, when he was the director of the International Cord Blood Society (ICBS), a precursor to the Perinatal Stem Cell Society. Mr. Cetrulo organized the 5th and 6th ICBS Congresses in 2002 and 2004, with participation from representatives across 23 countries. From 2000 to 2008, Mr. Cetrulo worked with cord blood banks, both domestic and international and both public and private. In 2008, Mr. Cetrulo co-founded Auxocell Laboratories, which achieved profitability in three years under his leadership. Mr. Cetrulo was a guest editor of the Stem Cell Reviews journal special edition focused on Perinatal Stem Cells in 2006, and then was an editor for two editions of the book Perinatal Stem Cells (Wiley Press, 2010 and 2013). Working on these publications enabled Mr. Cetrulo to develop relationships with the world's preeminent stem cell researchers working in the perinatal stem cell field. In 2013, Mr. Cetrulo co-founded the non-profit Perinatal Stem Cell Society in order to provide a platform for collaboration and the dissemination of knowledge and information about perinatal stem cells. The 2nd annual Perinatal Stem Cell Society conference will take place March 2-4, 2016 in Aspen, CO USA. For more information: kyle.cetrulo@perinatalstemcells.com

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Royan Cord Blood Stem Cells Save A Life

Amir Hossein Rashidi

Amir Hossein Rashidi is a 12-year old boy from Iran, Fars Province, Shiraz. He became sick with a disease known as leukemia (ALL type 2) since he was only 4 years old. He underwent chemotherapy for a couple of times, but each time the disease relapsed after a short while. To save his life, the experts reached to the consensus that a stem cell transplantation would be the only solution.

Amir Hossein has two siblings whose bone marrow were not matched with him, while his younger brother, Amir Taha, was a perfect match. The matching baby brother had his cord blood saved in Royan Stem Cell Technology Company.

In the dim light of Amir Hossein's life, cord blood stem cells appeared as the early dawn.

A cord blood transplant from his baby brother saved Amir Hossein and opened a new horizon to his future life. This operation was performed in Shariati Hospital which is the main hematopoietic transplantation center in Iran. Amir Hossein is pictured here with Dr. Morteza Zarrabi, Managing Director of Royan. Today Amir Hossein wishes to become an engineer in the oil and gas industry and serve his country.

We know there are lots more young boys and girls just like Amir Hossein and we find ourselves accountable to them and to the whole human community. We are keen on helping children and families through cord blood banking and transplantation and we will move heaven and earth to put it into effect and bring all people's hope into existence.

Royan Stem Cell Technology Royan Stem Cell Technology operates a hybrid public/private cord blood bank that was founded in 2005 and works together with scientists, researchers and experts in the field of Immunology, Hematology and Oncology. Royan has branches in more than 23 cities throughout Iran and has grown to store over 50 thousand family cord blood units and over 5 thousand public donations of cord blood. Royan Cord Blood Bank will do its utmost to race ahead the path of success according to the mission and vision set in advance so that it plays its role in the region.

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Haploidentical Transplantation

Karen Ballen, MD

Karen Ballen, MD

What is a Haploidentical Transplant?

A haploidentical transplant (haplo) is a half matched stem cell transplant from a family member. Haplo donors can be parents, children, siblings, and sometimes cousins of the patient. A biologic parent or a biologic child is always a half match to the patient, based on genetics. A haplo transplant can be used when there is no matched sibling or unrelated donor. Recently there has been an increase in the number of haplo transplants, particularly in Europe (1).

What is the History of Haploidentical Transplants?

Haplo transplants have been performed for over 20 years, but initially were limited by the very high risk of graft vs host disease (GVHD), one of the immune complications of a transplant.

About a decade ago, doctors in Italy tried to limit the GVHD of haplo transplants by using complex techniques to remove the T cells (the cells that cause GVHD) from the haplo marrow (2). These techniques were successful in reducing the risk of GVHD, but led to increases in infection, and relapse of leukemia. In addition, it was difficult for other hospitals to reproduce the T cell depletion method.

What is New in Haploidentical HCT?

Strategies to limit GVHD without increasing relapse or infection are crucial to the success of haplo transplants. The use of post transplant cyclophosphamide, chemotherapy actually given after the transplant - usually on Day +4 and Day +5 after transplant - was pioneered at Johns Hopkins. This strategy has led to a low rate of GVHD and post transplant mortality.

In a recently published study, 372 patients at Johns Hopkins with leukemia and lymphoma received post transplant cyclophosphamide after a haplo transplant using reduced intensity conditioning (mini transplant). After three years, 40% of the patients were alive with no evidence of their cancer (3).

The original haplo transplants were done using bone marrow as the stem cell source. Peripheral blood stem cells (PBSC) can be safely substituted for bone marrow, with an overall survival of 48% at two years (4).

The main concern with haplo transplant is a high risk of relapse, particularly for patients with high risk diseases. An important advantage of haplo transplants is the feasibility and safety of giving a donor lymphocyte infusion (DLI) from the original donor if there is relapsed disease (5). The benefits of haplo transplants are the ready availability, low cost, and low transplant related mortality (TRM: death within the first 100 days post transplant, not due to relapsed disease). Relapse, however, may be a limiting factor.

Comparative Studies

To date there are no completed prospective studies that compare outcomes among haplo transplant, umbilical cord blood transplant, and unrelated donor bone marrow transplant.

Most retrospective studies show similar survival but different rates of GVHD, relapse, infection, and TRM. Two parallel phase 2 trials, one using haplo transplants (halpo) and the other double cord blood transplants (CBT), were completed by the United States Bone Marrow Transplant-Clinical Trials Network (6). Fifty patients were treated in each study; all patients received a reduced intensity conditioning regimen of fludarabine, cyclophosphamide, and low dose total body radiation. At one year, the TRM was higher after cord blood transplants (24% CBT vs 7% haplo), but the relapse rate was higher after haplo transplants (31% CBT vs 45% haplo). Disease-free survival in the two groups was comparable at one year (46% CBT vs 48% haplo), and again in a follow-up at three years (36% CBT vs 35% haplo) (7).

The first prospective randomized comparison of double cord blood transplants vs haplo transplants is now ongoing (BMT CTN1101 or NCT01597778).

Comparison of Stem cell Graft Sources Umbilical Cord Blood Haploidentical Related Donor One HLA Mismatched Unrelated Donor
Availability of Donor Good Excellent Difficult for minority patients
Cost US $25-$40,000 per cord blood unit about US $15K US $25-30,000 per donor
Availability of Donor Lymphocytes No Yes Maybe
GVHD risk Low High High
Infection risk High High Moderate
Relapse risk Moderate High Moderate

Conclusions:

In 2015, there are many graft sources that allow almost all patients to have a transplant donor: matched sibling, fully matched unrelated donor, mismatched unrelated donor, umbilical cord blood, or haplo transplant. The table above presents a comparison of haploidentical transplants with either cord blood or a mismatched unrelated adult as the donor graft source. In fact, the choice of graft source may be less important than other factors such as the disease status and organ function of the transplant recipient. No patient should be denied a potentially curative transplant due to lack of a donor.

Karen Ballen, MD, is the Director of the Leukemia Program at Massachusetts General Hospital in Boston, and a Professor of Medicine at Harvard Medical School. Dr. Ballen studied Medicine at Dartmouth College, completed an internship and residency at Beth Israel Hospital in Boston, and a fellowship at Brigham and Women's Hospital in Boston. Her clinical and research interests focus on care of patients with leukemia and patients undergoing bone marrow or stem cell transplants, and novel therapies for leukemia and transplantation. A particular area of specialty is cord blood transplantation for those patients who do not have matched bone marrow donors. For more information: kballen@partners.org.

References:

  1. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplantation 2015; 50:476-482. doi:10.1038/bmt.2014.312
  2. Aversa, F, Terenzi, A, Tabilio, A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23:3447-3454. doi: 10.1200/JCO.2005.09.117
  3. McCurdy SR, Kanakry JA, Showel MM, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood 2015; 125(19):3024-31. http://dx.doi.org/10.1182/blood-2015-01-623991
  4. Raj G, Pagliuca A, Bradstock K, et al. Peripheral blood hematopoietic stem cells for transplantation of hematologic diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant 2014; 20(6):890-5. http://dx.doi.org/10.1016/j.bbmt.2014.03.003
  5. Zeidan AM, Forde PM, Symons H, et al. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant 2014; 20(3):314-18. http://dx.doi.org/10.1016/j.bbmt.2013.11.020
  6. Brunstein CG, Fuchs EJ, Carter SL, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 2011; 118(2):282-8. http://dx.doi.org/10.1182/blood-2011-03-344853
  7. Eapen M, O'Donnell P, Brunstein CG, et al. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant 2014; 20(10):1485-92. http://dx.doi.org/10.1016/j.bbmt.2014.05.015