Pain, Symptoms, AEs, and Recovery after Second Unrelated Donor Collection of Marrow/Peripheral Blood Stem Cells Are Similar to Those of the First Donation
Authors: Stroncek David , Shaw Bronwen E. , Logan Brent , Kiefer Deidre Marie , Chitphakdithai Pintip , Switzer Galen E. , Shah Nirali N , Miller John P. , Confer Dennis L. , Pulsipher Michael A 
Published: October 2019

Abstract
Background: Pain, symptoms and adverse events (AEs) after first donation of bone marrow (BM) or mobilized peripheral blood stem cells (PB) from unrelated donor subjects have been well documented. However, little is known about the safety of second donation experiences.
Methods: Second donations of NMDP unrelated donors performed between 2004 and 2013 were evaluated (n=720). Two groups were studied; those where 1) the second donation was PB (PB-PB, n=362 or BM-PB, n=240), compared with the first donation experience of those making only one PB donation (PB, n=16,095), or 2) the second donation was BM (BM-BM, n=42, or PB-BM, n=76), compared with the first donation experiences of those making only one BM donation (BM, n=5,829). Recovery, modified toxicity criteria (MTC), pain, collection yield and serious adverse events (SAEs) were compared.
Results: Most second donations were for the same recipient (n=515, 72%); BM-PB donors (85%) vs PB-PB donors (68%, p<0.001) and PB-BM (46%) vs BM-BM (69%, p<0.001). There was no difference in sex, race, body mass index (BMI) or CMV status whether the second donation was PB or BM.
For second PB donations there was no difference in the use of a central venous collection catheter, need for a 2-day collection, G-CSF dose or procedure duration among the 3 donor groups. The total CD34+ cell yield for PB donors who only donated once (median = 657x106) was significantly higher (p<0.001) than that of the first (578x106) and second collections (543x106) for PB donors that donated twice, however, for PB-PB donors there was no difference in CD34+ cell yield between their first and second PB donations (p=0.199). For second BM donations there was no difference in the type or duration of anesthesia among groups, but the total nucleated cell (TNC) yield for BM donors who only donated once was significantly higher (p<0.001) than that of the first and second collections for BM donors that donated twice.
The major finding was that for donors who gave second donations of either PB or BM there were no significant differences in skeletal pain, common toxicities and recovery compared to donors who donated once (Figure 1a and 1b). In the second PB donation group multivariate analysis found that maximum skeletal pain (grade 2-4), maximum MTC (grade 2-4) and time of recovery were dependent on donor sex and age but not donor group. Maximum skeletal pain was also dependent on BMI and maximum MTC was also dependent on BMI, race and collection year. In the second BM donation group maximum skeletal pain was dependent on race, sex and CMV status and time of recovery was dependent on sex and age at donation. Neither was dependent on donor group.
Prognostic factor analysis of PB-PB and BM-PB donations revealed several important points concerning second PB donations (Table 1). a) There is an increased risk of MTC or skeletal pain if the first donation was BM and second was PB. b) High maximum MTC with first donation predicts high maximum MTC or pain with the second donation. c) High pain with first donation predicts similar pain with second donation. d) High BMI predicts high MTC with the second donation. e) >12 months between donations, high maximum MTC with the first donation and slower recovery after the first PB donation predicts slower recovery after the second donation.
Conclusions: Second PB and BM donation experiences were similar to first donation experiences for pain, MTC, recovery and SAEs, but yields of second grafts were overall lower for both PB and BM collections. Low first donation collection yield was associated with the need for a second donation. This data provides reassurance that second donations of either BM or PB do not increase risk to unrelated donors. Knowledge of the donor's first experience can help predict what to expect for their second donation and allows for appropriate counseling.

Disclosures
Pulsipher: Novartis: Consultancy, Other: Study Steering Committee; Jazz Pharmaceutical: Consultancy; Chimerix: Consultancy; Medac: Other: Housing support for conference.