The clinical management of DC is complex and randomized clinical trials are lacking. Following the model of the Fanconi Anemia consensus guidelines, treatment of bone marrow failure is recommended if the hemoglobin is consistently below 8 g/dL, platelets less than 30,000/mm3
, and neutrophils below 1000/mm3
]. The first consideration for treatment for any hematologic problem should be HCT, if there is a matched related donor, proven to not have DC by physical and laboratory examinations, mutation testing and/or telomere length assay. HCT from an unrelated donor can be considered, although a trial of androgen therapy may be chosen.
Based on experience in the NCI Cohort, patients with DC appear to be sensitive to androgens, and the dose must be adjusted to avoid such side effects as impaired liver function or behavioral problems (i.e. aggression, mood swings). Splenic peliosis occurred in two patients with DC receiving the combination of androgens and G-CSF, leading to the recommendation that this combination be avoided [28
]. G-CSF with erythropoietin has occasionally been useful but should not be used in combination with androgens. Failure of DC-related BMF to respond to the type of immunosuppression used in acquired aplastic anemia suggest that the original diagnosis was not correct [29
HCT is the only definitive treatment for marrow failure. A reduced intensity conditioning regimen tailored for patients with DC was described. Its goal is to minimize the peri-transplant and late toxicity associated with transplant. Two of the four evaluable patients in the study survived. One died due to an adenoviral infection. Another had graft failure, was re-transplanted, and had early evidence of engraftment, but chose to leave the hospital early following the second stem cell infusion and died of sepsis. Of the 2 patients that remain alive, both are engrafted. One was the recipient of a matched related peripheral blood graft, the other a recipient of an unrelated donor marrow infusion. HCT for DC is clearly a life-saving measure but has substantial risks either from toxicity due to radiochemotherapy or immune related complications including rejection and graft versus host disease. Workshop attendees strongly agreed on the need for ongoing studies focused on improving HCT outcomes in DC.
Comprehensive evaluations at diagnosis are suggested, and then ongoing monitoring should be tailored to each patient. Other clinical tests to consider for disease surveillance for DC include bi-annual complete blood counts; a baseline and then annual bone marrow aspirates, biopsies, and cytogenetics, liver ultrasounds especially for, but not limited to, those on androgens, and annual pulmonary function tests, gynecologic exams, and skin cancer screening by a dermatologist ().