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Update - Spring 2014


Transplant Innovation - Haploidentical Stem Cell Transplant: Are We Closer to a Universal Donor?

Comparison Among Alternative Hematopoietic Stem Cell Sources

Umbilical cord blood unit(s)

Advantages

Near-universal availability
Less GVHD per HLA mismatch

Disadvantages

High graft failure rate
Delayed immune reconstitution
High transplant-related mortality
Repeat donation unavailable
Expensive graft source (especially for multiple units)

Partially HLA-mismatched unrelated donor

Advantages

Near-universal availability
Repeat donation may be available
Faster engraftment

Disadvantages

High GVHD rate
High transplant-related mortality
Long time from referral to transplantation
Lower overall survival

HLA-haploidentical related donor

Advantages

Almost universally available
Repeat donation is available and feasible
Low transplant-related mortality
Less costly than cord blood units

Disadvantages
Higher risk of relapse

GVHD = graft-vs.-host disease; HLA = human leukocyte antigen

Donor availability remains one of the major challenges to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). “Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall and progression-free survival rates,” says Rabi Hanna, MD, Director of Cleveland Clinic Children’s Hematopoietic Stem Cell Transplant Program. Unfortunately, only about one-third of candidates for allo-HSCT have HLA matched siblings.

Alternative stem cell sources

“Advances in HLA typing have enabled us to get excellent results from appropriately HLA-matched unrelated donors,” Dr. Hanna says. “However, the chance of finding an HLA-matched unrelated donor varies significantly by the racial and ethnic background of the recipient.” The search for an HLA-matched unrelated donor is also hindered by the amount of time it takes from search initiation to donor identification, he says. For patients who lack HLA-matched siblings or appropriately HLA-matched unrelated donors, there are alternative sources of stem cells for allo-HSCT:

  • Umbilical cord blood unit(s)
  • A partially HLA-mismatched unrelated donor
  • An HLA-haploidentical related donor

See the table at right for advantages and disadvantages of each source.

More donor options through haploidentical transplantation

An HLA-haploidentical donor is one who shares identity with the recipient for one HLA haplotype on chromosome 6 and is variably mismatched for HLA genes on the unshared haplotype. Because each individual inherits exactly one HLA haplotype from each biological parent and passes on exactly one HLA haplotype to each biological child, any patient with a living parent or child has a potential HLA-haploidentical donor for stem cell transplantation, or haplo HSCT. Further, each sibling or half-sibling has a 50 percent chance of sharing exactly one HLA haplotype with a patient. “The major advantage of haplo-HSCT, which Cleveland Clinic Children’s is now offering to appropriate patients, is the opportunity it provides for nearly all patients to benefit from HSCT,” says Dr. Hanna. “This takes us a step closer to the concept of a universal donor.” Various haplo-HSCT protocols are being developed to individualize treatment choices for patients based on their particular disease, the condition they are in and their comorbidities.

“I strongly believe that every patient who needs a blood or bone marrow transplant to provide a potential cure should have the chance to be cured,” says Dr. Hanna. “HLA-haploidentical transplantation is a step toward achieving that dream.”

For more information on Cleveland Clinic Children’s Hematopoietic Stem Cell Transplant Program please visit us online. To refer patients to Dr. Hanna and colleagues in the program please call 216.444.3608.


New Pediatric Cath Lab Dramatically Reduces Radiation Exposure

Cleveland Clinic Children’s has opened a second cardiac catheterization laboratory equipped with new detector technology that reduces radiation to ultra-low levels. Approved by the FDA in March 2013, Seimens Healthcare’s Artis Q.zen system reinforces Cleveland Clinic Children’s commitment to the principle of ALARA – “as low as reasonably achievable”—when delivering radiation in the cath lab.

“The importance of this technology is that it is expected to reduce radiation exposure by as much as 50 percent without sacrificing image quality,” says Lourdes Prieto, MD, Director of the Pediatric Catheterization Laboratory in the Center for Pediatric and Congenital Heart Disease.

Ideal timing

The ability to obtain high-quality images with less radiation coincides with the growing importance of catheterization-based procedures. Percutaneous interventions are becoming more common, as many lesions previously requiring open-heart surgery are now treated with less-invasive techniques. Moreover, patients with congenital anomalies are living longer, only to need multiple catheterizations over their lifetime.

Technological advances

The Artis Q.zen system employs a crystalline silicon detector, which reduces electronic noise. This allows clear images to be obtained with less radiation than required with standard amorphous silicon detectors.

The new system is also equipped with a type of X-ray tube based on flat emitter technology that provides small focal sizes and strong, short X-ray pulses. This improves contrast and spatial resolution of small moving vessels.

Transfer technology

Another method of lowering radiation exposure is to decrease procedure times.

To this end, the older cath lab is equipped with 3D-2D registration technology, which allows anatomic structures from a prior cardiac MRI or CT scan to be superimposed on fluoroscopy. The cardiologists are currently testing pediatric applications of this application, which facilitates accessing a desired structure—for example a collateral vessel, pulmonary artery branch or pulmonary vein—by providing a roadmap visible on fluoroscopy.

“We expect it will likely result in decreased radiation exposure, as well as contrast administration,” says Dr. Prieto.

The older cath lab is also equipped for rotational angiography, which reveals the 3D anatomy of a structure.

“The ability to view a structure from all angles improves the diagnostic quality of the procedure and allows us to more accurately select the best angiographic angles for any given intervention,” says Dr. Prieto. “From this 3-dimensional data set, it is also possible to register the location of a vessel on fluoroscopy, which decreases the amount of time and radiation needed to access a desired structure.”

To refer a patient to the Cleveland Clinic Children’s Center for Pediatric and Congenital Heart Disease please call 216.445.5015 or toll-free, 800.223.2273, ext. 55015. To learn more about the services provided by our pediatric cardiologists and cardiothoracic surgeons, visit us online.


Who's New? Staff Spotlight

Leticia Castillo, MD

Chairman, Critical Care Medicine
Department: Critical Care Medicine
Location: Main campus
Phone: 216.444.6022
Email: CASTILL@ccf.org

Yasser Al-Khatib, MD

Department: Pediatric Cardiology
Location: Main campus, Canton, Lorain, Medina
Phone: 216.444.2430
Email: ALKHATY@ccf.org


CME from Cleveland Clinic Children's

Live CME

May 8-10, 2014
Perspectives in Pediatrics: From Theory to Practice
Cleveland Convention Center & Global Center for Health Innovation, Cleveland, Ohio

Cleveland Clinic Children’s is happy to announce its First Annual Pediatric Conference, to be held in Cleveland, Ohio, May 8-10, 2014. Join us as we explore the future of pediatrics in the new era, and discuss research and patient care across various pediatric specialties.

Free Virtual CME

The newest free online CME activities from Cleveland Clinic Children's includes, “The Approach to Pediatric Patients with Recurrent Fevers.” This is an interactive case-based lesson in Cleveland Clinic’s popular Disease Management Clinical Decisions series.