Aplastic anaemia (AA) affects 1-2 per million of the UK population. At least 50% of patients have a Paroxysmal Nocturnal Hemoglobinuria (PNH) clone, which may either require monitoring or concomitant management with the aplasia if clinical indications for eculizumab are fulfilled. There is a paucity of data available to guide concurrent treatment for AA and PNH.


The UK PNH National Service (Leeds and London) database was reviewed retrospectively. Patients commencing eculizumab within a year of AA treatment, or those treated for aplasia who were already established on eculizumab were selected. Response to AA therapy was assessed according to aplastic anaemia guidelines.


Twenty six patients were identified who were treated with eculizumab and immunosuppressive therapy (IST) concurrently. Median age 39.5 years (range 7-75). Median granulocyte clone immediately prior to eculizumab was 82%. Ten patients had severe AA, 15 non severe and one had hypoplastic MDS. Treatment varied as per national guidelines dependant on patient's age, patient choice, prior treatment and co-morbidities.

Eight patients received ATG and ciclosporin (median follow-up 21 months post ATG treatment), 14 patients received ciclosporin monotherapy (median follow-up from commencement of ciclosporin 29 months). One patient received androgens as a single agent achieving a partial response (PR),3 patients underwent haematopoietic stem cell transplant (HSCT) as initial treatment at the time of eculizumab and IST overlap (5 other patients received HSCT as discussed below).

Six of the 8 (75%) patients receiving ATG+Ciclosporin responded, one patient achieved complete remission (CR) and five PR, one of whom subsequently achieved a CR with androgen therapy. Two patients did not respond and both achieved a CR after HSCT. In five patients who had data available six months post ATG there was no change in the median granulocyte or monocyte PNH clone size.

Of 14 patients treated with single agent ciclosporin, 1 patient achieved CR; 7 PR, 2 of whom achieved a subsequent CR with further therapy ( androgens N=1, HSCT N=1); 6 had no response, 3 of whom received subsequent treatment, two HSCT (one achieved a CR and one died), and one eltrombopag (response awaited; follow-up 12 weeks) .

Three patients underwent HSCT during the defined entry criteria above. 2 had frontline HSCT, and 1 had a transplant due to late relapse following ATG and ciclosporin 6 years prior. Five other patients underwent HSCT as discussed above for second or third line treatment (ATG and ciclosporin N=2, ciclosporin single agent N=3). All transplant patients achieved a CR except 1 who died during the procedure. All 7 patients who survived transplant stopped eculizumab due to resolution of PNH. Six of 26 (9.8%) patients died,1 who achieved a CR with HSCT and died 2 years later of GVHD , two patients who had achieved a partial response to treatment one of whom died of infection, two had not responded to treatment, and one HSCT recipient died during the procedure.

Fourteen age matched controls not on eculizumab received similar therapies, 9 of whom received ATG and ciclosporin, median follow-up from ATG commencement 37 months. Four of the 9 had a CR, 1 had a CR then a relapse with no response to the re-introduction of ciclosporin, 3 had a partial response one of whom achieved a CR with androgens and 1 patient had no response achieving a CR with HSCT. 5 matched controls were treated with ciclosporin single agent, median follow-up from ciclosporin commencement 115 months. Two patients had a CR, 1 had a PR then relapsed, 2 had no response.


This is the largest reported cohort of patients receiving concurrent treatment for both AA and PNH. The presence of symptomatic PNH requiring complement inhibition should not influence AA treatment decisions. The response rates for IST in patients on eculizumab compared with age matched controls were similar, with similar numbers of patients achieving CR or PR with immunosuppressive therapy, suggesting no detriment to response to IST with concurrent eculizumab therapy. Therefore, patients with concurrent AA and PNH should be treated as per AA guidelines and PNH can be managed concurrently if required. This strategy will increasingly be required in the future, especially with improved life expectancy for PNH patients receiving complement inhibition therapy. Eculizumab therapy does not appear to affect response to IST for AA patients


Griffin:Alexion Pharmaceuticals: Honoraria, Other: Conference support. Kulasekararaj:Alexion pharmaceuticals: Honoraria, Other: conference support. Hillmen:Pharmacyclics: Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Abbvie: Research Funding. Munir:Alexion pharmaceuticals: Honoraria. Richards:Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding. Arnold:Alexion Pharmaceuticals: Honoraria. Riley:Alexion pharmaceuticals: Other: Travel for conference. Marsh:Alexion pharmaceuticals: Honoraria. Hill:Alnylam Pharmaceuticals: Consultancy, Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.

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