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Recent Breakthroughs in Pediatric Bone and Marrow Transplantation

September 2015 - Blood and Marrow Transplantation

Over the past 20 years, the treatment of many pediatric hematologic malignancies with hematopoietic stem cell transplantation (HSCT) has achieved astounding successes. However, reducing opportunistic infections and other adverse events associated with the procedure remains a concern. In addition, new treatment options are needed for the small percentage of children with hematologic malignancies who experience relapses after HSCT. Experts at the University of Minnesota Masonic Children’s Hospital’s Pediatric Blood and Marrow Transplantation Center are moving toward identifying solutions to these challenges, and their leading-edge research has resulted in several recent breakthroughs.

BMT transplant-day
— Blood and marrow transplant physicians at University of Minnesota Masonic Children’s Hospital prepare to infuse a patient. University of Minnesota Health physicians perform nearly 300 bone and marrow transplants in children and adults each year.

Speeding Neutrophil Recovery after Transplantation

Umbilical cord blood-derived HSCT is used for the two-thirds1 of patients who do not have an HLA-matched sibling donor.2 Unfortunately, neutrophil recovery is slower after umbilical cord blood transplantation than it is after bone marrow transplantation, and during this period, these patients experience a high risk of mortality from infections and related complications.3

Recently, University of Minnesota Health experts have pioneered the clinical use of a new technique for greatly expanding the population of hematopoietic stem cells (HSCs) available from a single unit of umbilical cord blood. A small molecule called Stem-Regenin1 can be used to expand HSCs up to 328-fold over the course of a 14-day culture. In a clinical trial, patients who received transplants of the expanded HSCs achieved neutrophil recovery after a median 11 days compared with 23 days in patients who received standard HSCT, a substantial improvement in immune system recovery.4

Treating Relapsed/Refractory Acute Lymphoblastic Leukemia

Relapsed and refractory acute lymphoblastic leukemia (ALL) are among the leading causes of cancer deaths in children. About 15% to 20% of children with ALL who achieve a first remission will experience a relapse.5 Despite treatment with combined chemotherapy and allogeneic HSCT, only 70% of these children will be cured.6 Patients with refractory ALL have an even poorer prognosis, with a long-term survival rate of 10-30%.7, 8

One lifesaving option may be chimeric antigen receptor (CAR)-modified T-cell therapy. In this treatment strategy, an engineered CAR protein is used to stimulate a T-cell response to the tumor cells. The CAR protein links an extracellular domain that recognizes CD19 to intracellular signaling domains of the T-cell receptor complex. During treatment, the patient’s own T-cells are collected and engineered in vitro to express CAR proteins on their surface. Once the cells are reinfused into the patient, the CAR proteins can engage with the CD19 antigen on the surfaces of malignant B cells. This engagement activates the CAR-modified T cell and stimulates a potent cytotoxic response, triggering programmed cell death of the tumor cells. University of Minnesota Health experts currently have an open clinical trial of CAR-modified T-cell therapy in pediatric patients with relapsed/refractory B-cell ALL. Early results have been very promising. (See Case Study. See also Specialty Update for information on the clinical trials.)


  1. Mogul MJ. Unrelated cord blood transplantation vs matched unrelated donor bone marrow transplantation: the risks and benefits of each choice. Bone Marrow Transplant. 2000;25 Suppl 2:S58-S60.
  2. Bertaina A, Bernardo ME, Caniglia M, et al. Cord blood transplantation in children with haematological malignancies. Best Pract Res Clin Haematol. 2010;23:189-196.
  3. Wagner JE, Kernan NA, Steinbuch M, et al. Allogeneic sibling umbilical-cordblood transplantation in children with malignant and non-malignant disease. Lancet. 1995;346:214-219.
  4. Wagner JE, Brunstein C, McKenna D, et al. StemRegenin-1 (SR1) expansion culture abrogates the engraftment barrier associated with umbilical cord blood transplantation. Blood. 2014;124:21.
  5. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14:e205-217.
  6. Wagner JE Jr, Eapen M, Carter S, et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014; Oct 30;371(18):1685-1694. doi: 10.1056/NEJMoa1405584.
  7. Schrappe M, Hunger SP, Pui C-H, et al. Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med. 2012;366:1371-1381.
  8. Duval M, Klein JP, He W, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010 Aug 10;28(23):3730-8. doi: 10.1200/JCO.2010.28.8852.

When to refer

The Pediatric Blood and Marrow Transplantation Center welcomes patient referrals at any time. We can be contacted by phone at 612-273-2800 or (toll-free) 888-601-0787. Reach us by email at or via fax at 612-273-2919. For urgent requests, contact the attending physician at any time or day: 612-365-1000.

When you contact us, please have the following information available:

  • Diagnosis and status of disease
  • Demographic information
  • A brief, 1-page medical summary outlining the patient's medical status and course of clinical treatment
  • Insurance information

Educational Presentations for Medical Staff

If you are interested in having one of our center’s physicians visit your clinic or hospital to talk about pediatric bone and marrow transplantation, whether in a Grand Rounds format or a visit, please contact Cindy Koslowski to discuss opportunities.

Collaborative Care

Blood and Marrow Transplantation Center patients have complex medical needs requiring the attention of many medical subspecialists. Our multidisciplinary team of healthcare professionals includes oncologists and hematologists, advanced practice providers, specially trained nurses, pharmacists, nutritionists, genetic counselors, social workers, and child-family life specialists. The referring provider plays a critical role in the care team, and we are committed to communicating with you about your patient within 72 hours of a consult. Further, our support to your patients and their families is not limited to the time surrounding the transplantation process. Thanks to our Program for Long-Term Care, you can rest assured that your patient will be followed by our team of experts for life, and we will maintain ongoing communication with you.

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