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Is It Possible to be a Stem Cell Donor for the Second Time: A Single-Center Report of 12 Consecutive Procedures


Objectives: The use of unrelated donors as a source of stem cells for patients with blood disorders continues to increase. Approximately 5% to 7% of unrelated stem cell donors are asked to donate stem cells a subsequent time to the same or a different patient. We investigated donors who accepted to be a donor for the second time between 2015 and 2021; donors were evaluated in terms of procedure-related complications, product quality, and donor follow-up in a JACIE-accredited (Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation).
Materials and Methods: Stem cell collections were performed in accordance with relevant standard operating procedures from healthy volunteer donors. Data on sequence of peripheral blood stem cell, bone marrow, and donor lymphocyte collection procedures; presence of complications during procedures; time between 2 donations; need for granulocyte colony-stimulating factor again; and first and second donation types were noted. Data on donor and stem cell products were determined using the hospital information management system.
Results: Our study included 12 donors (9 men and 3 women) who donated a second time within the specified date range. In the evaluation of the second donation types, 7 were lymphocyte collection donations, 4 were peripheral blood stem cell donations, and 1 was a bone marrow stem cell donation. In short-term and long-term follow-ups, there were no complications among the donors. In the second donations, targeted product values were reached.
Conclusions: Although it is safe to have a second donation from a donor for the same patient, collection centers may collect more products than requested from eligible donors.

Key words : Stem cell transplantation, Subsequent donation, Unrelated donor


Allogeneic stem cell transplantation is still the only curative option in the treatment of many hematological diseases. There are many variables that affect the success of the transplant, one of which is donor type. The first option in transplantation is to have a sibling donor who is fully compatible with HLA.1 If the patient does not have a compatible sibling donor, it will be necessary to screen compatible or haploidentical donors within the family. If all of these options are unfavorable, then fully compatible or partially unrelated donor opportunities should be used.1-4

In Turkey, the largest national bone marrow registry is TURKOK, which operates under the Department of Blood and Blood Products of the General Directorate of Health Services. Its aim is to create a pool with a high number of volunteer donors, to find the most suitable volunteer donor candidates for patients as soon as possible, and to provide the necessary coordination for transplantation.5 The increased day-by-day activities of TURKOK over time have made it easier to find donors for many patients in the registry in a short time.5

Stem cell donation can mainly be in the form of either peripheral blood (PB) stem cells or bone marrow (BM) collection under anesthesia.6 Today, 95% of transplants are through stem cells collected from PB by using apheresis techniques. Retrieval of BM is done less frequently. To collect PB stem cells, granulocyte colony-stimulating factor (G-CSF) is administered to donors subcutaneously for 4 or 5 days.6,7 Bone marrow procurement is an invasive procedure that takes place under anesthesia. After donation, donors have regular follow-up at stem cell collection centers; if the recipient develops relapse, a second transplant may be considered as a treatment option.6-9 For these circumstances, an unrelated donor is contacted again through the registry, and approval is obtained for the second donation. Occasionally, the patient may develop chimerism loss; for these cases, donor lymphocyte collection can be aimed to collect donors without need for G-CSF.10 Studies that have analyzed the effects of a second hematopoietic stem cell collection from donors are scarce. It may be suggested that the quality system used by the center may have a significant effect on the outcomes of the procedure.

In this study, our aim was to examine donors who became unrelated donors for the second time between 2015 and 2021 at a single center in terms of procedure-related complications, product quality, and donor follow-up.

Materials and Methods

Study plan
The study was approved by the Local Ethics Committee of Baskent University (KA21/239). This single-center, retrospective study was conducted between June 2015 and 2021 at the Baskent University Adana Adult Bone Marrow Transplant Center (European Society for Blood and Marrow Transplantation [EBMT] CIC No 589; Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT [JACIE] accreditation certificate No: 644). TURKOK donors who donated PB stem cells or BM once were compared with those who donated either product twice in terms of procedure-related complications, product quality, and donor follow-up.

Data on sequence of PB stem cell, BM, and donor lymphocyte collection procedures; presence of complications during the procedures; time between 2 donations; need for G-CSF again; and first and second donation types were noted. In addition, the product quality control results of stem cells procured for the second time were evaluated. The presence of short- and long-term complications was investigated by evaluating donor follow-up parameters after both the first and the second donation. In addition, for patient clinical and laboratory characteristics from external centers, e-nabiz, which is the National Electronic Central Health Recording System in Turkey (, was used.

Data collection
For our analyses, we evaluated the impact of the interval between donations, donor and patient demographics (patient age, sex, and diagnosis, need for central line), changes to yield of CD34 for PB stem cells, and total nucleated cells for BM collection. CD34 and total nucleated cell counts were performed with standard assessment methods. Clinical and laboratory results of donors were collected from the hospital information management system (Nucleus version 9.30.11; Monad Software), which uses the international terminology criteria (Common Terminology Criteria for Adverse Events; CTCAE version 4.0); CTCAE records adverse events and side effects that are encountered during mobilization, stem cell collection, and donor follow-up. Patient and donor data were recorded with use of TURKOK forms (TÜRKÖK KOR10). Stem cell and cellular product records were obtained from the Turunc (version 1.1) labeling and product inventory system. All data were checked by a data audit group to ensure data safety in accordance with JACIE standards.

Exclusion criteria
Donors with health conditions that prevented them from being a donor during health evaluations, related donors, pediatric donors, and donors who accepted donation only once were excluded from the study.

Inclusion criteria
All unrelated donors who agreed to provide a second donation after stem cell collection in our center were included in the study.

Standard workflow
The medical director of the apheresis unit is responsible for obtaining informed consent from unrelated donors and communicating with the BM bank. The coordinator of the BM transplant center organizes consultation appointments with cardiology and gynecology/urology departments for donors. A specialist family physician or a hematologist is responsible for the general examination of the donors. Finally, test results of donors are evaluated by the apheresis medical director, and the results are shared with TURKOK. The medical director of the apheresis unit notes donor compliance; administration of G-CSF is started at the apheresis unit.

Blood counts and mandatory infection disease markers were studied in all donors who accepted to be a donor for the second time. If the interval between the 2 donations was longer than 6 months, the donor medical examination was performed again in all donors.

Peripheral stem cell and donor lymphocyte collection
All donors received 10 ?g/kg/day filgrastim (Neupogen; Amgen-Roche) in 2 equal doses via the subcutaneous route for 4 days for mobilization of stem cells from BM into PB. Apheresis was performed using a Spectra Optia device (Terumo BCT) according to the manufacturer’s instructions, using standard operating procedures (SOPs; KIT-TU-003) compatible with JACIE standards. According to the relevant SOP, anticoagulation was achieved through administration of acid citrate dextrose A only at a ratio of 1:12 that of the inlet flow rate. Apheresis was performed until the total blood volume had been processed twice. Heart rate, electrocardiogram status, transcutaneous oxygen saturation level, and noninvasive blood pressure were monitored intermittently during each procedure. Donors were not given any supplements or drugs before the procedure.

Bone marrow donation
Bone marrow collection procedures were performed under general anesthesia. All BM donors underwent retrieval from both iliac crests of the pelvis. The upper limit of the retrieved BM volume was 15 mL/kg of the recipient’s weight and did not exceed 20 mL/kg of the donor’s weight. Bone marrow collection procedures were carried out by 2 hematologists and according to the relevant SOP (KIT-TU-004).

Statistical analyses
Statistical analysis was performed using SPSS software (version 17.0; SPSS Inc.). Statistical significance was set at P < .05.


From 2015, when the Turkish BM registry was founded, until 2021, there have been 340 total stem cell collection procedures conducted at our center. Within our study period, there were 12 donors (3.52%), which included 9 men and 3 women, who were donors for a second time. All donors gave consent for the second donation. The mean age was 36.1 ± 8.5 years for male donors and 37.1 ± 1.8 years for female donors.

Of the 12 recipients who underwent stem cell transplant through nonrelative donors, 6 were adult and 6 were pediatric patients. With regard to type of diagnoses of recipients, 4 had acute myeloid leukemia, 2 had myelodysplastic syndrome, 1 had Fanconi aplastic anemia, 1 had hemophagocytic lymphohistiocytosis, 1 had chronic myeloid leukemia, 1 had chronic granulomatous disease, 1 had myelofibrosis, and 1 had thalassemia major.

With regard to donation type in donors, 9 donors had PB stem cell as the first procedure type and 3 donors had BM collection under operating room conditions as the first procedure type. During the first and second donation processes of the donors, health checks were carried out in our center, with no obstacles detected for any of the donations.

When TURKOK workup forms were examined, we found that 3 recipients needed a second procedure because of loss of chimerism, 7 recipients needed a second procedure because of mixed chimerism, and 2 recipients needed a second procedure because of relapsed disease. In 1 recipient, a second donation was needed because loss of viability had developed as a result of freezing the BM product during the COVID-19 pandemic.

When we evaluated the second donation type in the 12 donors, we found that 7 donation types were donor lymphocyte collections (58.3%), 4 were PB stem cells (33.3%), and 1 was BM collection (8.3%). All donors with first donation type of PB stem cells had donor lymphocyte collection as the second donation type, with mixed chimerism as the diagnosis for all of the recipients. A loss of chimerism was reported in 1 recipient who had a second BM collection 24 months after the first donation. For the 4 donors who had PB stem cell collections for their second donation, 3 recipients had relapsed disease and 1 recipient had loss of chimerism.

Regardless of the donation type, the average time between the 2 treatments was 13.9 months (range, 2-39 mo), and the average time elapsed after the second donation was 10.2 months (range, 3-33 mo; Table 1). All donors who accepted to be donors for the second time were determined to be donors for the same patient. In the 2 donors who required G-CSF again after the first donation, 15 months had passed after the first donation in 1 donor and 39 months had passed for the other donor. In the donor with the shortest time between the 2 procedures (2 months), the first procedure was BM collection, and therefore growth factor was not used for this procedure, and the second procedure was PB stem cell collection.

For the 7 donations of lymphocyte collection as the second donation type, all of the recipients had developed mixed chimerism after the first transplant. The interval between the 2 procedures in donors who underwent lymphocyte collection was 10.14 months (range, 4-25 mo).

No serious adverse effects were detected in any of the donors during stem cell collection procedures. All apheresis procedures were performed with peripheral venous vessels.

Quality control studies of all products collected showed no deviations in CD34 and CD3 at both the first and second donations. All products were transported to the transplant center by a special courier company contracted by TURKOK. No negative incidents concerning product quality and transportation conditions were shown in our center or the transfer center regarding any product.

Donor health evaluations were made at 1, 3, 6, and 12 months after donation. No complications were detected in any of the donors during follow-up.


Evaluations of unrelated donors and the donation process have affected the informed consent process for donors. European Union Directives, international standards, and current guidelines on donor safety, informing donors about the entire process, obtaining consent from donors, and performing the necessary investigations and consultations must be considered to ensure that the unrelated donation process is managed correctly and on time.11-14 To achieve this, centers should determine criteria for donor selection, obtaining donor consent, evaluation, and donor follow-up.14 At our center, we have been using 2 SOPs for donors: one on donor selection, evaluation, and safety (SOP no. KIT-KU-006) and the other on the service level agreement with the Turkish Donor Registry (SOP no. KIT-TU-32).

Unrelated donor stem cell transplant activity has been increasing, and between 5% and 10% of donors may be asked to provide a subsequent donation of progenitor stem cells (PB stem cells or BM collection) or donor lymphocytes.10 The World Marrow Donor Association (WMDA) has recommend that donors must be made aware of the possibility of a subsequent donation request before the first donation.10 At our center, 12 of 340 unrelated stem cell donors were asked to donate again. When we evaluated the subsequent donation types in the 12 donors, it was remarkable that the donation types were 7 donor lymphocyte collections, 4 PB stem cells, and 1 BM collection.

Mobilization with G-CSF is a generally safe procedure with regard to late side effects. There is no strong evidence on hinderances to perform the procedure safely.2,3,15 However, 16 malignancies (3 hematological), 4 autoimmune diseases, and also allergic, cardiac, gastrointestinal events, as well as infections, have been reported as late adverse events.16 Although donors may be enthusiastic about a subsequent donation, exposing a healthy person to the side effects of G-CSF for a second time worries health care professionals. Volunteering is essential in stem cell donation. Demanding the same self-abnegation from a person for the second time is one of the difficult decisions for medical professionals. During these decisions, many factors are important, including the type of second donation, the time elapsed between the 2 donations, whether there will be a need for reinjection of growth factor, and exposure to the effects of anesthesia. In our study, there was no reluctance to be a donor in all volunteer donors. In addition, consent was obtained from the donors again in accordance with the second donation type.10

There are few studies on second-time donations for unrelated transplant procedures, and little is known about the experiences of individuals who donate PB or BM for a second time.6 Although there are studies on the long-term effects of G-CSF implementation, the most important factor that concerns physicians and volunteer donors is exposure to growth factor for the second time.7,10 Our knowledge about exposure to G-CSF for the second time in PB stem cell collection procedures is quite limited. Among the 12 patients in our study, G-CSF was applied to only 2 donors for the second time, and the interval between the 2 applications was 15 and 39 months (Table 1). Our follow-up results showed 1 of these donors is in month 21 after the second application and the other is in month 3 after application without any complications.

Recent studies have shown that donation-related symptoms for subsequent donations are similar to those for the first one.6 However, little is known about differences in stem cell mobilization and yields for subsequent PB stem cells and BM collection procedures. There are 2 reports on the effects of G-CSF administration on stem cell counts in healthy donors for the second time.17,18 In both of these studies, CD34-positive cell counts were found to be significantly lower in the second donation. In another study, in which donors were remobilized for the same recipients within 60 days of their first donation (potentially due to primary graft failure), the pre-apheresis CD34-positive cell count was decreased by 40% at the second collection.19 However, the final CD34-positive cell yield did meet the target doses in the second harvest.19 In our study, target CD34-positive cell counts in the product were achieved in both donors who were remobilized for the second time for collection of PB stem cells. It is noteworthy that BM was collected at 2 different times under anesthesia in only 1 donor in our retrospective study. In this 45-year-old donor, the interval between the 2 surgeries was 24 months and the donor has been followed up for 6 months without any problems. In 7 donors, the second type of donation was lymphocyte donation; this procedure requires no exposure to anesthesia or growth factor. Therefore, donor lymphocyte collection is a relatively safe and easy procedure for both related and unrelated donors. Regardless, donors may be asked whether they agree to storage of part of their donation for use as donor lymphocytes for the same recipient. For many registries, this is allowed as routine practice if excess cells are collected.10

With regard to observational research on unrelated donors, we may say that most of these studies are long-term and multicenter studies. However, our single-center study, which included patients seen at a JACIE-accredited center, on 12 subsequent donations over a 6-year period is also of value.

The increase in the pool of unrelated donors every day brings up ethical and medical discussions about these donors.3,20 Some of these discussion are on the application of growth factor and/or anesthesia to a healthy individual, exposure to catheters and other invasive attempts, and feelings of psychological and social pressure. When the WMDA’s report was examined, no side effects or serious adverse events were encountered in the short- and long-term follow-up of donors who donated for a second time.10

The policies of many registries of unrelated stem cell donors allow people to donate a second time to the same or a different person. We suggest that there is no contraindication to this practice. However, it is difficult to judge whether stem cell product values are affected by the second donation because the number of cases was very low in our study. When we evaluated outcomes in terms of patient, donor, and product safety, it is obvious that there is a need for guiding studies on second-time unrelated donations.


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DOI : 10.6002/ect.2021.0267

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From the 1Baskent University Adana Dr. Turgut Noyan Training and Research Hospital Apheresis Unit, Adana, Turkey; the 2Baskent University Medical Faculty, Physiology Department, Ankara, Turkey; the 3Baskent University Adana Dr. Turgut Noyan Training and Research Hospital, Hematology Clinic, Adana, Turkey; and the 4Baskent University Medical Faculty, Family Medicine Department, Ankara, Turkey
Acknowledgements: The authors gratefully acknowledge the efforts of the apheresis unit staff at Baskent University Adana Dr. Turgut Noyan Training and Research Hospital. The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Ilknur Kozanoglu, Baskent University Adana Dr. Turgut Noyan Training and Research Hospital, Yuregir 01250, Adana, Turkey