Study Design
For this retrospective, registry study, we gathered data from the
Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium
(FPBCC). The objectives of FPBCC are to identify pediatric HCT best
practices and improve survival of children receiving HCT in Florida.
FBPCC participation involves monthly virtual meetings, participation in
quality improvement projects, sharing data for retrospective trials, and
developing consortium-wide prospective clinical trials. FPBCC was
founded in 2018 and comprises 5 of the 6 pediatric transplant programs
in the state of Florida, USA. All FPBCC participating centers signed
memoranda of understanding and data use agreements and obtained
institution-specific IRB approvals for this retrospective data analysis.
All patients have signed the informed consent for data reporting.
Transplant centers report detailed data on consecutive hematopoietic
cell transplantations to the statistical center of the Center for
International Blood and Marrow Transplant Research (CIBMTR), and
compliance with this reporting is monitored by on-site audits. Data from
participating centers were downloaded from the enhanced data back to
center platform of CIBMTR and forwarded to the FPBCC statistical center
at the University of Florida (Gainesville, FL, USA), where data were
combined into a single set and analyzed.
We describe characteristics of pediatric HCT recipients, including
gender, age, race, performance score, diagnosis, type of transplant, and
number of pre-transplant comorbidities. Transplant characteristics
consist of type of donor, stem cell source, Human Leukocyte Antigen
(HLA) match, conditioning regimen, and regimen intensity. Outcomes data
include length of survival, cause of death, and incidence and grade of
GVHD. Our data set included information on timing and use of second
transplant; however, reasoning (e.g. early or late graft rejection) for
second transplant was not available and the dataset did not contain
details of donor lymphocyte infusions or details of GVHD prophylaxis
other than the use of serotherapy. Thus patients who required the
2nd or subsequent transplant (N=21) and those who
rejected the transplant but did not undergo a subsequent transplant
(N=3) were not included in this manuscript. Patients for whom the center
did not provide information on GVHD (N=3) were considered not-evaluable
for GVHD and excluded as well. Myeloablative regimens were defined as
those using one or more of the following: total body irradiation
>500 cGy for a single dose or >800 cGy for
fractionate, busulfan >7.2 mg/kg iv, melphalan
>150 mg/m2, or thiotepa ≥10 mg/kg.
Reduced intensity regimens were defined as those using melphalan ≤150
mg/m2, thiotepa <10 mg/kg, TBI
>200 cGy and ≤500 cGy as a single dose or ≤800 cGy
fractionated, busulfan ≤7.2 mg/kg. Non-myeloablative regimens used any
dose of ATG, fludarabine, cyclophosphamide, or TBI≤200 cGy. (7) Fully
HLA-matched unrelated bone marrow (BM) or peripheral blood (PB) donors
were matched at A, B, C, and DRB1 antigens by high-resolution typing.
For umbilical cord blood (UCB) donors, full match was defined as 6/6
HLA-antigen match (A, B, DRB1) by either low or high resolution. A
related donor was considered haploidentical if ≥ 2 different antigens
(A, B, C, or DRB1) were mismatched. CIBMTR gathers and reports the
highest grade of acute GVHD by one year post transplant following
criteria published by Przepiorka et al. (8) Although currently CIBMTR
gathers data on individual organ involvement with cGVHD based on NIH
Consensus Criteria, 2014, the data available through our platform
contained only information on extent of cGVHD by one year post
transplant.
cGVHD was reported as limited or extensive based on definition by
Shulman et al. (9) Limited cGVHD includes only localized skin
involvement and/or liver dysfunction, while any other organ involvement
is considered extensive.