Stem Cell Transplantation for Fanconi Anemia: A Survey of Decision-Making among Families in the US and Canada.

Fanconi anemia (FA) is a primarily autosomal recessive, genetically heterogeneous disorder of chromosomal instability associated with congenital anomalies, cancer susceptibility, and progressive bone marrow failure. Currently, hematopoietic stem-cell transplantation (SCT) is the only treatment that will restore normal hematopoeisis; transplant protocols and recommendations are modified routinely due to challenges with severe toxicities in pre-transplantation conditioning regimens as well as complications related to acute and chronic graft-versus-host disease. SCT may also increase the risk of subsequent solid tumors, particularly head and neck squamous cell carcinomas, and has a significant mortality rate among FA patients. Given these potential harms, the decision-making process about SCT in FA patients is complex. The purpose of this study was to survey FA patients and their families in the United States (USA) and Canada to gain a better understanding of the factors that influence their decisions about SCT. We explored how perceptions of the need and associated risks of SCT influence the choice to undergo SCT.

Individuals who were members of the FA family organizations in the USA and Canada were sent a self-report survey via a two-phase blinded mailing whereby non-responders from the first mailing were sent a second questionnaire. Parents and patients were queried separately. A single respondent was selected to represent each affected individual, according to the following selection hierarchy: mother as primary respondent, followed by father, adult patient, and spouse/significant other. Survey items about decision-making were adapted from The Beliefs about Medicines Questionnaire (Horne, Weinman, & Hankins, 1999) which assesses respondents' beliefs about the necessity, associated risks, and concerns regarding a medical intervention, in this case SCT. Each of the three predictor variables (necessity, risk and concern) was measured by core items rated on a 4-point Likert scale. The necessity subscale was measured by core items which evaluated the respondents' perception of the medical need for SCT. The risk subscale measured respondents' perceived likelihood that the patient would suffer from: physical or emotional side-effects of SCT, liver disease, infection, graft-versus-host-disease, infertility, post-SCT cancer, post-SCT leukemia, graft rejection, death, or hazards to future offspring. The concern subscale consisted of respondents' evaluation of the degree to which they were concerned about: physical or emotional side-effects of SCT, short or long-term side-effects, death, uncertainty about the procedure, effect of SCT on the patient's ability to do daily activities, financial difficulties, finding an adequate donor, and conflicts with religious or ethical beliefs. Logistic regression was used to examine the direct effect of each of the three predictor variables on the outcome variable, selection or refusal of SCT.

Respondents for 223 individuals with FA (44% of those surveyed) were included in this analysis. The median age of patients at the time of diagnosis was 4.8 years (0-41 years); the median age at the time of transplant was 9.1 years (1.7-41.2 years). The majority of respondents were mothers (85%); fathers represented 10% of the final sample. A majority of patients included in the present analysis had SCT (83%), and a smaller majority were living at the time the survey was completed (64%). The subscale items exhibited good internal consistency reliability (αa > 0.80). In bivariate analyses, only perceived necessity and risk showed significant relationships with the outcome variable, SCT (p < 0.01). However, in multivariate logistic regression analyses including all three predictor variables, only perceived necessity of SCT was significantly associated with the decision to undergo SCT.

This is the first study to explore factors related to the utilization of SCT in FA. Our results demonstrated that the majority of subjects opted for SCT and that perceived necessity and risk of SCT were significantly related to the decision, while concern related to the SCT procedure was not. The perceived necessity of SCT was the most important factor for decision-making. These results suggest areas of emphasis for future research and counseling of FA patients and their family members.

No relevant conflicts of interest to declare.