The method of bone marrow harvesting developed in the 1960s has been accepted throughout the world. A new stem cell source, peripheral blood stem cells (PBSC), was introduced in the 1990s, and cord blood is under investigation as another source.
In spite of the expansion of donor sources, the need to donate bone marrow stem cells twice remains in related transplantation as well as in unrelated donor banks. We at JMDP (Japan Marrow Donor Program) have accumulated data on bone marrow harvested twice from the same donor with at least 1 year between the two harvests as well as data from the recipients of those bone marrow donations. These data, obtained over the last 12 years, are presented.
In JMDP, donors are allowed to donate their marrow 1 year after the first donation. Generally, different patients receive marrow from a single donor. The volume of marrow to be obtained is strictly regulated by JMDP according to the weights of the donor and recipient, and the hemoglobin level of the donor. The speed of marrow harvesting is also restricted to less than 500 ml/30 min. Marrow is collected from the posterior iliac crest under general anesthesia, and, as of the end of 2005, PBSC harvesting was not yet permitted by JMDP.
The volume of marrow obtained, total nucleated cell number, cell concentration per recipient body weight, as well as pre- and post-operative laboratory data were reported by the institution. Recipient data are also reported 100 days after marrow transplantation by the institution where the transplant was performed.
The dates of neutrophil and platelet recovery are defined as the first day of an absolute neutrophil count more than 0.5 × 109/l for 3 consecutive days and the first day of a platelet count more than 50 × 109/l, unsupported by transfusions for 7 days after transplantation, respectively. Data are presented as mean±s.d. except where otherwise stated. The Student's t-test was used to compare variables, and the correlation between two variables was analyzed with linear regression.
JMDP, which was started in 1991, had collected 5305 bone marrow donations by the end of 2003. Meanwhile, a total of 137 donors donated their bone marrow twice. The mean age of these 137 donors was 32.5±6.9 years (range 20–48 years) at the time of the first donation, and 36 of them were women. Their mean weight was 64±9 kg (range 42–89 kg). The mean time interval between the first and the second donations was 3.9±2.0 years (range 1.4–9.6 years).
The results of the first and second harvests are shown in Table 1. The volume of marrow collected increased significantly in the second harvest (P=0.001). However, the mean weight of the recipients was also significantly higher in the second donation (P<0.001). Conversely, the total cell numbers collected were the same (P=0.674), and as a result, the cell concentrations of bone marrow solution were significantly lower in the second donation (P<0.001) as were the nucleated cell numbers per recipient weight (P<0.001).
Collection speed and volume collected per time were also evaluated. Cell collection took longer in the second harvest (P=0.001) but the mean volume of marrow collected per time did not show any significant difference (P=0.51).
Comparing the incidence of adverse effects of bone marrow donations, including fever of more than 38°C, urinary pain, sore throat, infectious diseases, liver dysfunction and pain from the wound lasting for more than 7 days and the duration of the febrile period, no significant differences were observed between the first and second donations.
The efficacy of the harvested cells was also evaluated by comparing the available data from 127 pairs of patients who received marrow from the same donors. There were no differences between the first and second marrow donations in the dates of neutrophil recovery (P=0.521) and platelet recovery (P=0.411). There were two cases of slow engraftment (up to Day 35) a piece after the first and second donations, and late rejection in 1 and 5 patients, after the first and the second donation (P=0.213).
In related transplantation, second harvest usually occurs within a short period of time for the same recipient, because of the rejection of the cells initially transplanted. Conversely, because of the shortage of appropriate donors, an unrelated donor might be asked to donate his or her marrow twice for different recipients.
Several reports have discussed second marrow donations. Buckner et al.1 reported the data from 99 donors who donated marrow twice within 2 months. The average number of total cells collected in the second donation tended to be lower. Stroncek et al.2 reported the data from second donations collected from 16 donors. Their total cell numbers and cell concentrations were lower in the second donation, especially when the second donation was performed within 90 days after the first one. These lower cell concentrations in the second harvest, however, might be owing to a short time interval between the two harvests; a comparison of the efficacies of those cells has never been performed.
IBMTR also reported 117 donations harvested twice through early 1997. Out of these 117 donors, 76 provided a second bone marrow donation without major complications. Details of these donations and efficacy of cells, however, have not yet been reported.3 World Marrow Donor Association: international standards for unrelated hematopoietic stem cell donor registries did not mention second donation.4
According to the data obtained from 137 second bone marrow donations performed in JMDP, a second harvest can be performed safely and the functions of cells in the second harvest were as good as those of the ones donated first. However, because the cell concentration of the second donation may be lower, it may be necessary to collect more marrow than anticipated.
Buckner CD, Clift RA, Sanders JE, Steart P, Bensinger WI, Doney KC et al. Marrow harvesting from normal donors. Blood 1984; 64: 630–634.
Stroncek DF, McGlave P, Ramsay N, McCullough J . Effects on donors of second bone marrow collections. Transfusion 1991; 31: 819–822.
Confer DL . Hematopoietic cell donors. In: Blume KG, Forman SJ, Appelbaum FR (eds). Thomas’ Hematopoietic Cell Transplantation, 3rd edn. Blackwell Publishing Ltd: Malden, MA, USA, 2004, pp 538–549.
Hurley CK, Raffoux C . World marrow donor association: international standards for unrelated hematopoietic stem cell donor registries. Bone Marrow Transplant 2004; 34: 103–110.
We thank Dr Hideki Origasa for the discussion about statistical matters.
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Akiyama, H., Hara, M., Hino, M. et al. Second donation of bone marrow: results from the Japan Marrow Donor Program (JMDP). Bone Marrow Transplant 37, 795–796 (2006). https://doi.org/10.1038/sj.bmt.1705322
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