Lack of association between relationship status and clinical outcome in allogeneic stem cell transplantation—the Swiss Transplant Cohort Study

It has been known for decades that social conditions influence physical and mental health. Berkman et al. proposed a conceptual model of how social networks impact health, recognizing the role of upstream factors such as cultural and socioeconomic elements and elaborating on downstream factors such as psychosocial mechanisms and pathways.1 In this framework, marital or relationship status is a structural aspect of social network, which creates the conditions for social support, in turn impacting health through various mechanisms.

A growing number of studies has shown that marital status is correlated with outcome of cancer patients including analyses from single malignancies2, 3 as well as larger population based studies.4, 5 However, there are limited data published on the influence of relationship status in allogeneic stem cell transplant (HSCT).

HSCT patients are a particular patient population in that they often suffer from a malignant disease with a significant risk of relapse6 and are at risk for multiple complications.7 Hence there are multiple conceivable ways in which a caregiver or spouse could be beneficial. For this reason we studied if being in a stable partnership at the time of transplant or experiencing a change in relationship status post transplant predicted outcome parameters in the context of the Swiss Transplant Cohort Study (STCS).

The STCS is a prospective multicenter cohort study started in 2009 for HSCT. At time of transplant, a written informed consent is obtained for extended prospective data collection and sampling.8 Selected socio-demographic, psychosocial and quality of life variables are collected using the Psychosocial Questionnaire (PSQ) pre-transplant, 6 and 12 months posttransplant, and yearly thereafter.9

We included all patients transplanted between September 2009 and February 2015 who were included in the STCS from all three Swiss stem cell transplant centers (Zurich, Geneva and Basel). Only first allogeneic transplants were included. Children<18 years of age as well as autologous and syngeneic transplants were excluded. We merged the STCS dataset containing all psychosocial data with the EBMT dataset containing disease and HSCT related data.

Relationship status is assessed in the STCS by 1 item. Patients indicate their relationship status at each measurement point since August 2012 in one of the 5 answer categories: (1) single, (2) married/stable partnership/cohabitation, (3) widowed, (4) divorced/dissolved partnership/separated or (5) refusal to answer. Before August 2012 Version 1 of the PSQ was used, which had 2 minor differences: divorced and separated were two separate answers, and stable partnership was not mentioned, so that the respective answer read ‘married/cohabitation’. For the purpose of this study we used 2 operational definitions derived from this measurement. The first was being in a stable partnership (answer 2) versus single (combination of answers 1,3 and 4). The second was experiencing a change in relationship status post transplant, meaning relationship status post transplant differed at least once from relationship status pretransplant, for example being in a stable partnership at the time of transplant and single at 1 year posttransplant.

Patient characteristics were compared using Pearson’s χ2 test for categorical and Mann–Whitney U-test for continuous variables. The Kaplan–Meier method was used to estimate overall survival (OS) and PFS (progression-free survival), while the rate of relapse, GvHD (graft-versus-host disease) and non-relapse mortality (NRM) were calculated with the cumulative incidence (CI) method. CI of GvHD was calculated treating death without GvHD as a competing event, CI of NRM was calculated treating relapse as a competing event, and CI of relapse was calculated treating death in remission as a competing event. Disease risk index was calculated according to Armand et al.10

Between September 2009 and February 2015, 715 patients received an allogeneic transplant who fulfilled the inclusion criteria. Patient characteristics according to relationship status are shown in Table 1.

Table 1 Patient characteristics according to relationship status at transplant

Relationship status at time of transplant was provided by 640 patients. Of the remaining 75, 32 provided information on relationship status at 6 months post transplant, leaving 47 patients without information on relationship status. The majority of patients indicated being married/stable partnership (n=470, 66%), 14% (n=102) of patients were single, 11% (n=83) were divorced/separated, and 2% (n=13) were widowed. Four patients (1%) indicated that they refused to answer, and 43 (6%) did not provide an answer. Patient characteristics did not differ between those with or without a stable partnership with the exception of age, with single patients being significantly younger (Table 1).

Since information on relationship status was queried with every PSQ, it was possible to analyze the change of relationship status over time. 483 patients provided information on relationship status at more than one timepoint. 441 (91%) of these had no change in relationship status, while 9 and 15 changed from single to stable partnership and stable partnership to single, respectively. In 18 patients, there was more than one change over time. Median time of first change in relationship status was 345 days (156–730) post transplant.

The median follow-up of survivors was 748 days (60-2213). The median OS and PFS was 4.4 years and 2.0 years respectively, with a 3 year OS and PFS of 56 and 47% respectively. The CI of NRM at 3 years was 14%, the CI of relapse after 3 years was 38%. The CI of acute GvHD (aGvHD) I-IV at day 100 was 50% with a rate of 11% of aGvHD III-IV. Information on aGvHD was missing in 71 patients. The CI of chronic GvHD (cGvHD) at 3 years post transplant was 47%, 16% had extensive and 31% had limited cGvHD.

We then analyzed the association of relationship status before transplant and outcome parameters. There was no difference in OS or PFS for patients with or without a stable partnership; however, patients without information on relationship status had a significantly worse OS (Figure 1) and PFS (not shown) than those with information (OS P<0.001, PFS: P=0.001 for missing versus others).

Figure 1
figure1

Overall survival according to relationship status.

There was no difference in incidence of NRM, relapse, aGvHD or cGvHD between patients with and without a stable partnership. To control for an interference of age and relationship status or other disease and transplant related factors we performed a multivariable analysis (including relationship status, age, sex, education, Karnofsky, disease, disease risk index, time from diagnosis to transplant, donor sex mismatch, conditioning intensity, use of TBI, graft source, year of transplant) which confirmed the lack of influence of relationship status on the various outcome parameters. When looking at change in relationship status as a time-dependent covariate, there was no influence on OS or PFS, incidence of NRM, relapse, acute and chronic GvHD.

Since due to the wording of version 1 of the PSQ some patients in stable partnership might have been missed, we performed a secondary analysis of patients included before August 2012. This analysis confirmed the lack of influence of relationship status on all outcome parameters measured. As in the original analysis, those with missing information on relationship status had inferior OS and PFS. For details see Supplementary Table 1 and Supplementary Figure 1.

Few other studies have looked at the influence of relationship or marital status in the stem cell transplant population. One small study analyzed the association of psychosocial factors and 1 year mortality in 85 patients and found no association.11 Two recent and larger studies also failed to find an association between marital status and GvHD, transplant-related mortality or overall survival.12, 13

While our results are in accordance with these studies, they were somewhat surprising due to the convincing evidence from a wide range of other settings in which married patients have a favorable outcome. The discrepancy with studies in large cancer registries4, 5 could possibly be explained by the quite unique situation of HSCT patients. However other studies in situations more similar to allogeneic transplantation such as renal transplant and HIV have also confirmed the positive influence of a stable partnership.14, 15

We can only speculate on the reasons for the lack of association of relationship status and outcome after allogeneic transplant. Pathways through which relationship status could influence outcome include financial and social support among others. In Switzerland, the large part of health care costs is covered by mandatory health insurance, reducing the impact of financial resources. Also it is possible that patients undergoing such intensive treatment require a close network supplanting stable partnership where not available.

A further finding in our analysis was the significantly worse outcome of patients with missing information on relationship status. A possible explanation for the association of missing values and outcome is that patients in poor general condition were not well enough to fill out the PSQ. This is one of the drawbacks of our study, though due to the relatively small number of patients with missing information, we assume that this did not significantly influence the results. Further drawbacks include the fact that due to the wording of the first version of the PSQ in use until 2012, we might have missed some patients in stable partnership, as well as the fact that we could not differentiate between patients who were married or in cohabitation, since there is data indicating that being married may have a unique influence on heath parameters that is not compensated for by a supportive network.16

In conclusion, our analysis shows that relationship status has no significant influence on outcome. While this is in contrast to results from other populations, it is reassuring that single patients are not at a disadvantage and that the post-transplant care provided is possibly comprehensive enough to compensate for any lack of support single patients might have.

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Acknowledgements

This study has been conducted in the framework of the STCS, supported by the Swiss National Science Foundation and the Swiss University Hospitals (G15) and transplant centers.

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Correspondence to S Gerull.

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The members of the Psychosocial Interest Group

L Berben9, H Burkhalter9, V Claes9, S De Geest9, K Denhaerynck9, R Helmy9, M Kirsch9, L Leppla9, O Mauthner9, M Struker9, A Boehler10, S Gerull10, MT Koller10, U Huynh-Do11, E Boely12, E Catana13, A Simcox14, A Seiler15, R Klaghofer15, I Binet16, P Künzler-Heule16 and S Beckmann17

9University of Basel; 10University Hospital Basel; 11University Hospital Inselspital Bern; 12University Hospital Geneva; 13University Hospital Lausanne; 14University of Lausanne; 15University Hospital Zurich; 16Cantonal Hospital St Gallen and 17University of Basel; University Hospital Zurich

THE MEMBERS OF THE SWISS TRANSPLANT COHORT STUDY

R Achermann, P Amico, J-D Aubert, V Banz, G Beldi, C Benden, C Berger, I Binet, P-Y Bochud, H Bucher, T Carell, E Catana, Y Chalandon, S de Geest, O de Rougemont, M Dickenmann, M Duchosal, L Elkrief, T Fehr, S Ferrari-Lacraz, C Garzoni, PG Soccal, C Gaudet, E Giostra, D Golshayan, K Hadaya, J Halter, D Heim, C Hess, S Hillinger, HH Hirsch, G Hofbauer, U Huynh-Do, F Immer, R Klaghofer, M Koller (Head of the data center), B Laesser, R Lehmann, C Lovis, P Majno; O Manuel, H-P Marti, PY Martin, P Meylan, (Head, Biological samples management group), P Mohacsi, P Morel, U Mueller, NJ Mueller (Chairman Scientific Committee), H Mueller-McKenna (Head of local data management), A Müller, T Müller, B Müllhaupt, D Nadal, M Pascual (Executive office), J Passweg, J Rick, E Roosnek, A Rosselet, S Rothlin, F Ruschitzka, U Schanz, S Schaub, A Schnyder, C Seiler, S Stampf, J Steiger (Head, Executive Office), G Stirnimann, C Toso, C Van Delden (Executive office), J-P Venetz, J Villard, M Wick (STCS coordinator), M Wilhelm and P Yerly.

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Gerull, S., Denhaerynck, K., Chalandon, Y. et al. Lack of association between relationship status and clinical outcome in allogeneic stem cell transplantation—the Swiss Transplant Cohort Study. Bone Marrow Transplant 52, 1686–1688 (2017). https://doi.org/10.1038/bmt.2017.204

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