The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Defining the Unique Late Effects of Children Undergoing Hematopoietic Cell Transplantation for Immune Deficiencies, Inherited Marrow Failure Disorders, and Hemoglobinopathies

Abstract

An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled, “Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Non-malignant Hematologic Disease was held in Minneapolis, Minnesota on May 10–11, 2016. The purpose of the conference was to address the unmet need for a greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for nonmalignant disorders. The conference focused on transplantation for hemoglobinopathy, immune deficiency, and inherited bone marrow syndromes. A multidisciplinary group of experts in the disease areas and transplant late effects presented the current state of understanding of how the underlying disease, pretransplant therapies, and transplant related factors uniquely interact to influence the development of late toxicities. Recommendations were put forth by the group for the late effects screening of survivors of transplantation for these non-malignant disorders. The findings and recommendations that came from this conference will be presented in a series of six additional manuscripts in the upcoming months. In this manuscript we explore the need for screening practices specific to the survivors of transplantation for non-malignant diseases and the metholodologic challenges associated with the study of these patients.

Late Effects Screening Guidelines after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement From the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects After Pediatric HCT

“…General HCT follow-up guidelines have been created, 28–31 reviewed, 32 and are summarized in Table 1. These guidelines do not consider pre-transplant exposures or disease-specific manifestations that are unique to patients with nonmalignant hematopoietic disorders, and cannot be readily interchanged with exposures for malignant disease such as chemotherapy and radiation.…”

Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders

“…Patients who received HLA matched sibling grafts and those with performance scores 90–100 had significantly superior survival at 100 days, 1 year, and 3 years post HCT, approaching 80%. Given the larger experience in patients with other nonmalignant diseases showing very low mortality, further studies of treosulfan-based conditioning in patients with DBA are warranted to determine if equivalent or better survival can be achieved without the potential late effects of busulfan and TBI, such as growth retardation, gonadal toxicity, or secondary malignancies [30–34]. …”

A single‐center experience using alemtuzumab, fludarabine, melphalan, and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease

“…2,4,5 Myeloablative conditioning regimens for HCT are associated with significant morbidity, including sinusoidal obstruction syndrome (SOS), acute and chronic graft-versus-host disease (aGVHD and cGVHD), infections, and death. 4,6,7 To minimize transplant-related complications while preserving donor engraftment, recent efforts have centered on identifying optimal reduced-intensity conditioning (RIC) regimens for patients with CGD.…”