Acquired Aplastic Anemia (AA) and Paroxysmal Nocturnal Hemoglobinuria (PNH) are ultra-rare diseases with a yearly incidence 2 to 4 per million (AA) and of 1.3 to 2 per million (PNH. While much is known about pathophysiology and treatment of these interrelated diseases, less is known about patients (pts.) psycho-social issues. Quality of life (QoL) evaluation tools used in all studies for AA and PNH are rather unspecific and were initially designed for cancer patients (e.g. the European Organization of Research and Treatment (EORTC) QLQ-C30). Given the complexity of AA and PNH, the variation in symptoms and different treatment approaches (immunosuppression, bone marrow transplantation, complement inhibition or others and eventually sequences of all in some pts.), the often young age of the pts., and the fact that marrow failure syndromes are not classified as malignant diseases, it is likely that the cancer-specific questionnaires used so far are inappropriate to adequately assess the QoL and illness intrusiveness in these pts.Based on these considerations and funded by German patient support groups (Aplastische Anämie e.V., pnh-aa.info), we therefore initiated the development and validation of an AA/PNH-specific QoL-instrument (QLQ-AA/PNH).


Generation of a QLQ-AA/PNH was performed according to EORTC QoL group guidelines, i.e. after identification of QoL issues by literature review, a focus group of pts. and physicians were interviewed (phase I). After screening of documented interviews, QoL issues were generated and reworded in a preliminary questionnaire (phase II). In phase III the questionnaire with generated items was evaluated in a representative group of patients. Pts. were recruited through participating physicians, the internet and through word-of-mouth by other pts., pts. internet forums and pts. conferences. Individual pts. in more than 25 German and Swiss cities were visited and personally interviewed. Currently, psychometric validation of the final questionnaire is ongoing through patients included in the German PNH-registry. Eventually, the QLQ-AA/PNH will be further evaluated as part of a prospective clinical interventional trial performed within the European Group for Blood and Marrow Transplantation Working Party Aplastic Anemia (EBMT WP-AA). In addition, patients were asked to complete a questionnaire regarding their supportive care needs, (e. g. informations, support by medical staff, psychosocial counseling, patient support groups.) and potential iatrogenic problems (e. g. delay in diagnosis, appreciation of QoL problems by health care professionals).


In phase I, 19 pts. and 8 physicians specialized in treatment of AA/PNH were interviewed. 649 resulting QoL issues were condensed to 175, which were then again graded according to their importance by 30 pts. (10 AA, 10 PNH, 10 PNH/AA), and 14 physicians (phase II). Altogether, 97 issues were rated important. Physicians rated fatigue the most important issue while pts. rated mutual trust between physicians and pts. as the most important QoL-aspect. 11/30 EORTC QLQ-C30 issues (e.g. loss of appetite, nausea, vomiting, constipation, diarrhea) were not mentioned or rated unimportant, while several new QoL aspects such as constant fear of infection and blood count variations, dependency on time-consuming therapies, and emotional strain through endlessness of disease burden were brought out. Modifications in wording and phrasing led to two questionnaires with 67 items regarding general QoL-aspects and further 20 items regarding medical care, which are currently being evaluated through interviews with 35 additional patients. The final questionnaire with no more than 40 items will then be validated.


A detailed summary of the relevant items or questions will be presented. Up to now important QoL-aspects of PNH/AA pts. are inappropriately captured or missed the with available EORTC-QoL-tools. Even in ultra-orphan diseases industry independent development of disease specific QoL-tools is feasible with support of pts. and pt. advocacy groups.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.