[Paediatric palliative care: multidisciplinary and pro-active]. / Kinderpalliatieve zorg: multidisciplinair en proactief.

Every child with a life-limiting or threatening illness, and his or her family, has a right to palliative care. Palliative care is not limited to end-of-life care, but starts from the moment of diagnosis and is independent of whether there are curative options. To optimise quality of life of both the child and the family, the emphasis of care should be on both somatic and psychosocial and spiritual aspects from the very start, and goals should be set together with the child and the family. A multidisciplinary and pro-active approach is essential if this is to be achieved. It is, therefore, strongly recommended that at least every academic hospital should have a multidisciplinary paediatric palliative care team.

Donors' health state the year after peripheral haematopoietic progenitor cell collection: A prospective follow-up study in related and unrelated donors compared to first-time platelet donors.

Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral haematopoietic progenitor cells collected by apheresis (HPC-A) are the most common source used for allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective short and long-term donor follow-up studies show very low risks of serious complications and do not report compelling evidence of increased cancer occurrence. Some studies reported a prolonged period of leucopenia without an obvious association with infectious complications. However, beyond the first few weeks after the procedure a relationship between events is elusive. We therefore evaluated medical service utilization by prospectively recruited HPC-A donors and first-time platelet apheresis donors for comparison for 1 year after donation. Data were prospectively collected using questionnaires and by medical record review. A total of 215 HPC-A donors (111 unrelated donors and 104 related donors) and 96 first-time platelet donors consented to participation in the study. Follow-up was available for 202 (96%): questionnaires were returned by 74% and records from nonstudy contacts were available for 94% of donors. During the 1-year follow-up, 94 of the donors who returned questionnaires sought medical attention for diagnostic evaluation and/or treatment: 41% of HPC-A donors and 40% of platelet donors. Medical service utilization the first year after HPC-A donation is similar to that after first-time platelet donation. The occurrence of serious medical conditions in both related and unrelated HPC-A donors underscores the importance of participation in long-term follow-up in large cohorts. The findings in this relatively small cohort contribute to evidence on the safety of G-CSF mobilization and HPC-A. J. Clin. Apheresis 31:523-528, 2016. © 2015 Wiley Periodicals, Inc.

Related hematopoietic cell donor care: is there a role for unrelated donor registries?

In almost half of allogeneic hematopoietic progenitor cell (HPC) transplants, a related donor (RD) is used, yet a lack of standardized guidelines means that their care is heterogeneous. Changes to regulatory standards aim to improve uniformity, but adherence to these regulations can prove logistically difficult for the transplant centers (TCs) managing RDs. Discussion has ensued around possible alternative models of related donor care and a session at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting in 2013 debated the question of whether a role exists for unrelated donor registries in the management of 'related' donors. In this overview, we discuss the issues raised at this debate and the pros and cons of donor registry involvement in various aspects of RD management. By examining existing models of related donor care that have been adopted by members of the World Marrow Donor Association (WMDA), we look for ways to enhance and homogenize RD care, while also enabling transplant centers to meet standards required for mandatory accreditation.

Unrelated adult stem cell donor medical suitability: recommendations from the World Marrow Donor Association Clinical Working Group Committee.

The World Marrow Donor Association (WMDA) fosters collaboration between international registries to facilitate the exchange of hematopoietic stem cell products for unrelated stem cell donor transplantation. As indications for hematopoietic SCT grow, the movement of products across the world will increase. Although competent authorities may regulate products within their country, there is a need to protect the best interests of donors and recipients by identifying universal donor medical suitability criteria. Within this report the WMDA provides a background to unrelated adult donor and recipient safety, recommends a common framework for assessing the health of unrelated adult donors at each stage of the donation pathway and presents a novel mechanism for sharing international consensus criteria for individual medical and lifestyle conditions. Wherever possible, these criteria are evidence-based. By establishing a donor medical suitability working group, the WMDA has developed a process through which donor centers and registries may request a consensus opinion on conditions not already listed, as well as challenge existing criteria. Guidance from the WMDA is intended to complement, not supersede, guidance from national competent authorities and international regulatory bodies.

Immediate and long-term somatic effects, and health-related quality of life of BM donation during early childhood. A single-center report in 210 pediatric donors.

Since 1968, when Leiden undertook the first successful European pediatric BM transplantation with a 7-year-old sibling donor, more than 300 young children have donated BM in our unit. We first retrospectively studied a cohort of 210 donors, younger than 13 years at donation, to survey procedures of donor eligibility and study immediate effects of BM donation. We then performed a long-term follow-up (FU) and health-related quality of life (HRQoL) study. Despite documentation of previous medical conditions, no child was declared unfit to donate. We found that iron deficiency anemia or low-iron stores in BM did not result in treatment or extended FU. Harvest volumes exceeded 15 mL/kg in 65% of donors, with more than half requiring allogeneic blood transfusions. Donors had no structured FU after their first post-donation control. In this study, 25% of donors reported at least one somatic complaint at long-term FU. Finally long-term HRQoL revealed high scores in most subdomains (representing a higher QoL), compared to norm groups. These results indicate the need for development of (inter)national guidelines for pediatric stem cell donor care management.

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT.

The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing ≥ grade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of ≥ grade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

Allogeneic hematopoietic stem cell donation-standardized assessment of donor outcome data: a consensus statement from the Worldwide Network for Blood and Marrow Transplantation (WBMT).

The number of allogeneic hematopoietic SCTs performed globally each year continues to increase, paralleled by an increased demand for donors of therapeutic cells. Donor characteristics and collection procedures have undergone major changes during recent decades, and further changes are foreseen. Information on short- and long-term donor outcomes is of crucial importance to ensure maximal donor safety and availability. Current data, predominantly from unrelated donors, give reliable information on the frequent early events associated with donation-most of them of mild-to-moderate intensity. Information on the type and relative risk of serious adverse reactions is more limited. Moreover, only few data exist on long-term donor outcome. On the basis of this need, recommendations for a minimum data set for prospective donor follow-up were developed in a workshop with the participation of an international group of investigators actively involved in allogeneic stem cell donation under the auspices of and approved by the Worldwide Network for Blood and Marrow Transplantation. Establishment of a standardized global follow-up for both, related and unrelated, donors will enable monitoring of the short- and long-term safety profiles of hematopoietic cell donation and form a solid basis for future donor selection and counseling.

Managing a dual role--experiences and coping strategies of parents donating haploidentical G-CSF mobilized peripheral blood stem cells to their children.

UNLABELLED: Hematopoietic stem cell transplantation is an effective therapy for life-threatening hematological diseases. Parents may be asked to donate hematopoietic stem cells for their child when no compatible related or unrelated donor is available. OBJECTIVE: Parents donating G-CSF mobilized peripheral blood stem cells simultaneously and uniquely fulfill the dual role of donor and caregiver for their ill child. The experiences of both sibling and unrelated stem cell donors have been extensively reported but not those of parental donors. METHODS: We therefore undertook a study specifically to investigate the experiences and coping strategies of parental stem cell donors. In-depth qualitative interviews were conducted with 13 parental donors, which were subsequently transcribed and subjected to thematic analysis. In addition, parental coping was assessed utilizing the Utrecht Coping List. RESULTS: Qualitative analyses revealed four main thematic categories describing the way parental stem cell donation was experienced, namely 'Hope and Fear', 'Need for Information', 'Do Anything for your Child' and 'Transplant Outcome' In addition parents noted similar difficulties which were unrelated to their specific role as a donor, for example they felt socially isolated. CONCLUSIONS: Individual information for the parents needs to address not only the transplantation procedure but particularly those aspects related to the donation process. We feel there is a need for a protocol specifically designed to support and coach parental donors.

Family donor care management: principles and recommendations.

The World Marrow Donor Association (WMDA) is an international organization fostering collaboration in clinical transplantation and promoting the interests of unrelated stem cell donors. The WMDA has developed standards for the recruitment, counseling, work-up and subsequent donations to protect the interests of donors. Although the care of family donors has been carefully considered and managed in transplant centers (TCs) internationally over numerous years (and increasingly TCs are facing accreditation programs, which address this issue) there is currently a lack of standardized guidelines for the management of family donors. The underlying principles of family donor care are in many ways identical to those concerning unrelated donors, although key ethical considerations differ. Although the WMDA is primarily involved in the field of unrelated donors, we believe that it is important to collaborate with those involved with family donors, to standardize the care. This document hopes to encourage increased collaboration between those caring for related and unrelated donors, and build on the extensive work, which has already been undertaken in this field to homogenize care. We recognize that there will be financial, regulatory and logistic differences in different countries and that the manner in which these principles are achieved may vary.

Hematopoietic stem cell donor selection: the Europdonor experience.

International collaboration is essential for the optimal selection of unrelated hematopoietic stem cell donors. This review focuses on the benefit of a joint worldwide donor file called Bone Marrow Donors Worldwide and the experience of the Europdonor Foundation in selecting strategies to identify the best human leukocyte antigen-matched donor in the shortest time.

How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more!

Many patients do not reach haematopoietic stem cell transplantation. Shortage of unrelated donors (UDs) is still seen as the main cause. However, with a worldwide UD pool containing more than 8 million donors, it is possible that other impediments are becoming more important. We analysed 549 UD searches for Dutch patients, performed between 1987 and 2000, in order to find the reasons for failure or success to reach transplantation. Between 1996 and 2000, 59% of the patients of Northwest European origin received a graft from an UD with a median time span of 4.4 months from the start of the search. In all, 11% of the patients lacked a compatible donor, while 30% became medically unfit for transplantation. This is in contrast to the patients of non-Northwest European origin for whom UD shortage is still the most important impediment; only 32% were transplanted while 50% lacked a compatible donor. We conclude that the shortage of donors is no longer the biggest constraint in unrelated stem cell transplantation for patients of Northwest European origin. It may be more effective to optimize the chance on transplantation by making the search process more efficient.

The importance of identifying a back-up donor for unrelated stem cell transplantation.

The importance of identifying a back-up donor, once a primary suitable unrelated stem cell donor has been found, is often underestimated. Transplant centres erroneously count on the unrelated volunteer donors to be willing, available and medically fit for actual donation. According to our data, which includes 502 unrelated donor work-up procedures performed for 425 Dutch patients between 1987 and 2002, one of 11 work-ups ended in the primary requested donor failing to donate. Of all donor-related cancellations (N=46), 78% of the procedures were deferred due to medical reasons and 22% due to nonmedical reasons. Most of the donors deferred for medical reasons were female (P=0.005). In 50% of the cases for which a back-up donor was already identified, the patients were transplanted with a delay of less then 2 weeks; when no back-up donor was available, the median delay increased to 18 weeks. We strongly encourage implementing a search for at least one back-up donor in the primary search. Identifying a back-up donor can save precious time and complicated logistic rescheduling.