Immunosuppressive Therapy and Future Response to Androgens or Survival After Hematopoietic Stem Cell Transplantation in Fanconi Anemia.

A large proportion of patients with Fanconi anemia (FA) develop aplastic anemia (AA), which is unlikely to respond to immune suppressive therapy (IST). It is not known whether exposure to IST might have a negative effect on patients' response to other therapeutic interventions or their cancer risk. We therefore surveyed FA patients in the United States and Canada to determine whether treatment of AA with IST (perhaps inadvertently prior to the diagnosis of FA) jeopardized subsequent response to anabolic steroids or survival following hematopoietic stem cell transplantation (HSCT), or increased the risk of a malignancy.

With the help of Fanconi Anemia Research Fund (FARF) and Fanconi Canada (FC), we sent surveys to 905 adults including patients and their parents or other care providers. A single primary respondent was identified for each patient, using the following priority order: mother, father, adult patient or other care provider; each patient was thus accounted for only once. The survey ascertained age, gender, reason for diagnosis of FA, vital status, treatment, HSCT outcome and development of cancer or leukemia. IST was defined as treatment with cyclosporine A, antithymocyte globulin, or intravenous immunoglobulin. The frequencies of androgen responders, HSCT survivors, and malignancy among FA patients who received IST were compared with those who did not receive IST.

We received responses representing 224 FA patients. The median age (range) of the patients was 17.3 years (2.6-54.4), the male:female ratio was 114:110, and the overall survival was 144/224 (64%). Single, double or pancytopenia led to the diagnosis of FA in 138 of the 224 patients (62%). Fifty-eight of the 224 patients received IST (26%), 74 received androgens (33%), 121 underwent HSCT (54%), and 23 developed a malignancy (10%). Fifteen patients had solid tumors and 9 had leukemia. One patient developed both a solid tumor and leukemia. Twenty-three of 30 (77%) who received androgens after IST reported a response, compared with 51 of 58 (88%) androgen recipients who had not received IST (p = 0.2). Thirty-two of 53 (60%) patients who had prior IST survived HSCT, while 45 of 68 (66%) without IST for AA also survived HSCT (p = 0.6). Three of 58 (5%) patients developed a malignancy after IST compared with 20 of 166 (12%) without IST (p = 0.2).

Treatment of AA in a patient who is subsequently diagnosed with FA does not appear to have negative or positive effects on later response to androgens, survival following HSCT, or the risk of malignancy. The limitations of this study are its retrospective nature, the inclusion of multiple family members as the respondents, the inability to ascertain the timing of IST, and its dependence on self-report. The apparent lack of not only harmful but beneficial effects of IST raises questions about its utility for the treatment of AA in FA patients, and suggests that the use of IST may lead to delay in appropriate management.

No relevant conflicts of interest to declare.