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Toxicity in related versus unrelated HSC donors
Univariate analyses of peripheral blood stem cell collection, pain and donation-related symptoms
Figure 2A and B show rates of grades 1-4 skeletal pain and MTC symptoms in RD and URD before, on day +5 of G-CSF administration (day of peak symptoms), and one year after the PBSC collection procedure. Online Supplementary Figure S2A-D detail locations of pain and types of symptoms experienced by RD and URD undergo- ing PBSC collection. Online Supplementary Table S4 shows that at pre-donation baseline, day +5 of G-CSF, and one year, all measures of grade 2-4 and 3-4 pain are higher in RD compared to URD (all P<0.001). In addition, 10% fewer RD return to pre-donation levels of pain at one year (P<0.001). Collection-related MTC symptoms are also experienced significantly more and to a higher degree at all time points, and non-recovery to pre-donation levels of these symptoms at one year occurs more often after RD procedures (17% vs. 12%; P<0.001).
Multivariate analyses of bone marrow and peripheral blood donor experiences: related versus unrelated donor
Multivariate analysis showed that Grade 2-4 pain after BM collection was similar between RD and URD (Table 2). Grade 2-4 symptoms after BM collection were 1.5 times more likely for RD, but this did not reach signifi- cance (P=0.075). Related PBSC donors were at higher risk for grade 2-4 and 3-4 pain (OR 1.42, 8.91, respectively; both P<0.001) and grade 2-4 symptoms (OR 1.84; P<0.001) with collection, as well as the presence of grade 2-4 symptoms at one year (OR 1.56; P=0.021). A notable finding was that RD reporting no comorbidities had a risk of grade 2-4 pain at one year similar to URD. But if RD reported any comorbidities, their risk of grade 2-4 pain was significantly increased, with the highest risk noted in
RD with comorbidities that would have led to deferral by NMDP standards (OR 3.43; P<0.001).
Table 2 also describes analyses of failure to recover to pre-donation levels of pain and donation-related symp- toms at one year. RD of PBSC had an OR of 1.42 for non- recovery to pre-donation levels of pain at one year (P=0.001). Recovery to pre-donation levels of symptoms was associated with comorbidity: RD who had no comor- bidities were similar to URD, but RD who had comorbidi- ties had a higher risk of non-recovery at one year. Notably, RD identified as having comorbidities that would have led to NMDP deferral had a more than 3-fold increase in risk of non-recovery to pre-donation levels compared to URD (OR 3.71; P<0.001).
Multivariate analysis: other factors affecting risk of pain, symptoms, or non-recovery at one year
For BM donation, women were 67% more likely to experience grade 2-4 pain and nearly 3 times more likely to experience grade 2-4 symptoms (P<0.001) (Table 3). Age was an important risk factor for failure to recover to pre-donation levels, as donors aged 50-60 years were more than twice as likely as their younger counterparts to have non-recovery at one year (Table 4). In addition, women’s risk of non-recovery at one year to pre-donation levels of symptoms was twice that of men (P<0.001).
Risk factors for pain and MTC symptoms after PBSC collection included both new and previously described clinical characteristics (Tables 3 and 4). A new finding is that high CD34+ counts (≥80.5/mL) prior to day 1 of collec- tion was associated with more grade 2-4 collection pain (OR 1.25; P<0.001). Another novel finding was that there was a dose level of G-CSF above which pain levels increased significantly. If a donor received an average daily dose exceeding 960 mg/day, reported pain levels were
Table 2. Multivariate analysis of collection toxicities and long-term recovery after bone marrow (BM) and peripheral blood stem cell (PBSC) donations showing the effect of donor type. The odds ratios are for comparing related donor (RD) versus unrelated donor (URD).
Event and time point
Skeletal pain
Grade 2-4 at collection Grade 3-4 at collectiona Grade 2-4 at one yeara
RD, comorbidities absent
RD, comorbidities present, acceptable RD, comorbidities present, indeterminate RD, comorbidities present, defer
Non-recovery to pre-donation level at one year
Max MTC symptoms
Grade 2-4 at collection
Grade 2-4 at one yeara
Non-recovery to pre-donation level at one year
RD, comorbidities absent
RD, comorbidities present, acceptable
RD, comorbidities present, indeterminate
RD, comorbidities present, defer
BM donors
OR (95% CI) P
1.19 (0.81-1.74) 0.375
0.96 (0.56-1.63) 0.871
1.50 (0.96-2.36) 0.075 1.08 (0.58-2.01) 0.819
PBSC donors OR (95% CI)
1.42 (1.17-1.72) 8.91 (6.63-12.0)
1.02 (0.63-1.65) 2.66 (1.60-4.42) 1.62 (1.04-2.52) 3.43 (1.86-6.35) 1.42 (1.15-1.74)
1.84 (1.49-2.28) 1.56 (1.07-2.27)
0.94 (0.64-1.37) 1.98 (1.26-3.12) 1.77 (1.24-2.52)
3.71 (2.14-6.45)
P
<0.001 <0.001 <0.001 0.944 <0.001 0.033 <0.001 0.001
<0.001 0.021 <0.001 0.743 0.003 0.002
<0.001
OR: odds ratio; CI: Confidence Interval; Max: maximum; MTC: Modified Toxicity Criteria. aNumber of events for BM donors was not sufficient for multivariable analysis.
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