Blood and Marrow Transplantation and Cellular Therapies

Mission

The mission of the Division of Blood and Marrow Transplantation and Cellular Therapies (BMT&CT) at UPMC Children's Hospital of Pittsburgh is to design and test disease-specific and biologically rational novel reduced-toxicity transplantation regimens for patients with high-risk leukemia or lymphoma and for those afflicted with life-threatening inherited conditions that can lead to bone marrow failure, immune deficiency, autoimmune diseases, and neurodegenerative conditions. Less-intense chemotherapy is combined with risk-tailored and pharmacologically personalized immunosuppression. Post-transplant cell therapy is offered to decrease disease recurrence and reduce infectious complications, with the overarching goals to improve quality of life and disease-free survival after cord blood or bone marrow transplantation.

Overview

The Division of BMT&CT was established in July 2011 upon the arrival of Paul Szabolcs as division chief from Duke University. Before Dr. Szabolcs arrival, the division was called the Blood and Marrow Transplantation (BMT) Program and operated as a part of the Pediatric Hematology/Oncology Division and averaged 20 to 24 transplants a year.

In 2017, the BMT&CT division had five faculty physicians with clinical activities. Since the arrival in August 2014 of Craig Byersdorfer, a clinician-scientist, all clinical transplant services have been provided by members of the BMT&CT division. The division is poised to perform 40-50 transplants per year over the next two to three years and to open novel clinical protocols that will primarily recruit patients from out of state.

We are the only center in the world with the ability to successfully engraft children suffering from sickle cell disease, thalassemia, and many other disorders with reduced intensity regimen paired with a single unit, HLA-mismatched cord blood graft (ClinicalTrials: NCT01962415). A CliniMacs® device has been successfully implemented since 2012 to support novel clinical trials with T-cell-depleted autologous transplantation for Crohn’s disease and T-cell-depleted human leukocyte antigen (HLA)-mismatched allogeneic bone marrow transplantation, all approved by the U.S. Food and Drug Administration (FDA) as an Investigational New Drug (IND).

We are the only center in the world to offer tandem lung and bone marrow transplantation for pediatric and adult patients with immune deficiencies who have progressed to pulmonary failure recovering organ and marrow from the same deceased HLA-mismatched unrelated donor. This programmatic effort is supported by NIAID/NIH and mechanistic laboratory studies will analyze acquisition of mucosal immunity and tolerance.

The division is also a part of the new UPMC Immune Transplant and Therapy Center (ITTC), which opened in 2018. The ITTC, a partnership between the University of Pittsburgh and UPMC, focuses on exploring the power of the human immune system in three main areas: organ transplantation, cancer, and aging. Through the ITTC the division will expand its transplant research through several clinical trials. 

Clinical Activities

During the academic year of 2017, the division performed 38 transplants. The majority of the transplant grafts were procured from unrelated allogeneic donors with unrelated cord blood (UCB) grafts being most common. By 2016, the use of unrelated bone marrow grafts had exceeded HLA-matched sibling marrow transplant numbers. Autologous mobilized stem cell rescue is performed for children with high-risk neuroblastoma and brain tumors. Haploidentical transplants were performed by both in vitro T-cell depletion and by post-transplant cyclophosphamide administration. With all possible transplant modalities on site, we can find a suitable donor for any patient who may benefit from hematopoietic stem cell transplantation (HSCT).

One of our signature protocols (ClinicalTrials: NCT01962415) has attracted patients from two dozen states, ranging from Florida to Alaska. Patients with ~20 unique genetic diagnoses enrolled on this reduced-intensity conditioning (RIC) trial. Diagnoses ranged from sickle cell disease, thalassemia, osteopetrosis, Krabbe disease, MLD, too many primary immune deficiency syndromes such as BLS, and XIAP deficiency. Day 100 non-relapse mortality (NRM) has remained exceptionally low; there have been no deaths during this most vulnerable transplant period. With over three dozen patients enrolled so far, one-year event-free survival exceeds 90% in the unrelated cord blood transplant setting, exceeding the results of centers of excellence worldwide. In 2016 the division opened an institutional prospective trial for children and young adults afflicted with high-risk acute myeloid leukemia (AML), employing RIC and Myeloablative Conditioning (MAC) for HSCT in AML/MDS (ClinicalTrials: NCT02626715). To bridge the temporary post-transplant immune deficient state, we have performed therapeutic T-cell infusions with adenovirus hexon-specific interferon gamma-captured cells under IND/Institutional Review Board (IRB) approved treatment plans. These will pave the way for new protocols that we plan to open in 2018 taking advantage of a new CliniMACS ®Prodigy device and conceptual advances.