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Toxicity in related versus unrelated HSC donors
ABSTRACT
Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to dona- tion, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unre- lated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P<0.001] and severe (OR 8.91; P<0.001) pain and toxicities (OR 1.84; P<0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; P=0.021) and non-recovery from pain (OR 1.42; P=0.001) at one year. Related donors with more significant comorbidities were at espe- cially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (P=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the relat- ed donor experience, and decisions regarding donor deferral. Registered at clinicaltrials.gov identifier: 00948636.
Introduction
Donation of hematopoietic stem cells (HSC) in the form of bone marrow (BM) or peripheral blood stem cells (PBSC) is a commonly performed procedure, with more than 40,000 donations from both volunteer unrelated donors (URD) and related donors (RD) each year.1,2 Over the past decade, donor registries such as the National Marrow Donor Program (NMDP) have published detailed data describing the URD experience, identifying individu- als at increased risk for pain and collection-related symp- toms, slower recovery, and severe adverse events.3-7 Data describing the RD experience, however, are limited, with only one large recent study.8 This may be because URD are handled by registries that have a mandate to collect and report safety data, whereas RD are cared for by local transplant centers, whose primary focus is care for the recipient and, in most countries, RD safety data are not systematically collected. Inadequate data regarding RD is a cause for concern for many reasons. While URD reg- istries have rigorous standards for donor approval, sup- ported by internal quality initiatives and efforts at interna- tional standardization,9 there are no generally accepted guidelines about deferral of a RD.
With these concerns in mind, North American Investigators teamed with the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research (CIBMTR) to conduct a prospective observational trial of RD who donated at 53 transplant centers in the United States between January 2010 and July 2014. This report describes our primary end point comparing pain, toxicities and recovery of RD with URD collected concurrently at 78 BM and 87 PBSC NMDP collection centers.
Methods
Prior to donation, RD underwent a medical evaluation including a detailed history, physical examination, blood tests, and addition- al work up as necessary according to center standards. RD approved for donation were approached for consent for this Institutional Review Board (IRB)-approved study.
Unrelated donors provided written informed consent for partic- ipation as required by the NMDP IRB. URD were evaluated for medical suitability and comorbidities that would require further evaluation or qualify for deferral for BM or PBSC donation as spec- ified by NMDP standards.10,11
Data collection
A pre-donation form including history of pre-existing medical conditions (comorbidities) was completed. Detailed collection- related symptoms and pain were collected at five time points: pre- donation, peri-donation [day +5 from start of granulocyte-colony stimulating factor (G-CSF) for PBSCs and 1-2 days after BM collec- tion], and 1, 6 and 12 months post donation. Toxicity was defined by Common Toxicity Criteria measures for symptoms commonly noted during PBSC and BM collection (fever, fatigue, skin rash, local reactions to an injection, nausea, vomiting, anorexia, insom- nia, dizziness, and syncope) and is called the Modified Toxicity Criteria (MTC). This approach was validated by the NMDP and has been published previously.4,5,12,13 Pain was graded from 0-4 as none, mild, moderate, severe, or disabling. Pain and toxicity meas- ures were assessed by the transplant center at pre- and peri-dona- tion time points; the CIBMTR Survey Research Group was responsible for follow-up assessments.
A product-specific collection form detailed information on the collection procedure. A subset of donors underwent assessment of long-term psychological recovery by established Health Related Quality of Life instruments (reported previously14-16).
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