CONCURRENT TREATMENT OF APLASTIC ANEMIA (AA) WITH IMMUNOSUPPRESSIVE THERAPY AND PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) WITH ECULIZUMAB
(Abstract release date: 05/19/16)
EHA Library. Griffin M. 06/09/16; 133030; E1481
Disclosure(s): Dr M Griffin, Professor P Hillmen, Dr T Munir, Mr S Richards, Louise Arnold, Kathryn Riley and Dr A Hill have either served on advisory boards, received honoraria or research funding from Alexion pharmaceuticals
Dr. Morag Griffin
Contributions
Contributions
Abstract
Abstract: E1481
Type: Eposter Presentation
Background
At least 50% of aplastic anaemia (AA) patients have a PNH clone. Many have a small proportion of PNH cells requiring monitoring alone whereas others may present with both significant aplasia as well as PNH. Concurrent treatment for AA and PNH may therefore be required.
Aims
This retrospective analysis assess's the outcome of patients with concurrent PNH and aplastic anaemia who require complement blockade with eculizumab alongside immunosuppressive therapy (IST) for AA
Methods
The PNH National Service database (Leeds) was reviewed retrospectively. Patients who commenced eculizumab within a year of their aplastic anaemia treatment, or those treated for aplasia who were already established on eculizumab were selected.
Results
Fourteen patients were treated with eculizumab and immunosuppressive therapy concurrently. Median age was 38.5 years (range 7-76). AA treatment varied as per national guidelines dependant on the patient’s age, patient choice and co-morbidities. Seven out of fourteen received ATG and ciclosporin (median follow-up 20 months post ATG), six received ciclosporin monotherapy (median follow-up from commencement of ciclosporin 97 months). 6 of the 7 patients receiving ATG+Ciclosporin responded, two achieved complete response (CR) and four a partial response (PR), one of whom required tacrolimus and subsequently achieved a CR with androgen therapy and one who achieved PR with oxymetholone. One did not respond and achieved a CR with a bone marrow transplant (BMT). Median granulocyte count reduced from 88% to 50% post ATG treatment however there was no change in the monocyte PNH cloneOf the six patients treated with ciclosporin monotherapy, one had a CR with concurrent androgen therapy, two had a PR, one had a CR then relapsed and is now in PR on recommencement of ciclosporin, two had no response. There was no change in the granulocyte PNH clone following ciclosporin treatment. One patient proceeded to first line bone marrow transplantation (mean follow-up from presentation 7 months). Both BMT recipients stopped eculizumab post transplant due to resolution of PNH. Two patients died, one from infection following a PR with ATG and ciclosporin, and one from unknown causes who had not responded to treatment. One patient had spontaneous remission of their PNH and stopped eculizumab; the remaining nine patients continue on eculizumab.Fourteen age matched controls not on eculizumab received similar therapies, nine of whom received ATG and ciclosporin (median follow-up from ATG commencement 37 months). Four had a CR, one had a CR then relapsed with no response to re-introduction of ciclosporin, one had a PR and two had no response, one of whom had a BMT with CR and one achieved CR with oxymetholone. One ATG patient is awaiting response (four months post ATG). Five patients were treated with ciclosporin monotherapy (median follow-up from ciclosporin commencement 115 months). Two had a CR, one had a PR then relapsed, one had no response and achieved a PR with oxymetholone and one is awaiting response (three months post ciclosporin commencement).
Conclusion
Concurrent treatment of AA with IST and PNH with eculizumab has not previously been reported. 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 IST. Eculizumab therapy does not appear to affect response to IST for aplastic anaemia patients.This strategy may be required especially with improved life expectancy for PNH patients receiving complement inhibition therapy. The patients in this study were treated in accordance with current aplastic anaemia guidelines and the presence PNH should not influence this.
Session topic: E-poster
Keyword(s): Aplastic anemia, Immunosuppressive therapy, Paroxysmal nocturnal hemoglobinuria (PNH)
Type: Eposter Presentation
Background
At least 50% of aplastic anaemia (AA) patients have a PNH clone. Many have a small proportion of PNH cells requiring monitoring alone whereas others may present with both significant aplasia as well as PNH. Concurrent treatment for AA and PNH may therefore be required.
Aims
This retrospective analysis assess's the outcome of patients with concurrent PNH and aplastic anaemia who require complement blockade with eculizumab alongside immunosuppressive therapy (IST) for AA
Methods
The PNH National Service database (Leeds) was reviewed retrospectively. Patients who commenced eculizumab within a year of their aplastic anaemia treatment, or those treated for aplasia who were already established on eculizumab were selected.
Results
Fourteen patients were treated with eculizumab and immunosuppressive therapy concurrently. Median age was 38.5 years (range 7-76). AA treatment varied as per national guidelines dependant on the patient’s age, patient choice and co-morbidities. Seven out of fourteen received ATG and ciclosporin (median follow-up 20 months post ATG), six received ciclosporin monotherapy (median follow-up from commencement of ciclosporin 97 months). 6 of the 7 patients receiving ATG+Ciclosporin responded, two achieved complete response (CR) and four a partial response (PR), one of whom required tacrolimus and subsequently achieved a CR with androgen therapy and one who achieved PR with oxymetholone. One did not respond and achieved a CR with a bone marrow transplant (BMT). Median granulocyte count reduced from 88% to 50% post ATG treatment however there was no change in the monocyte PNH cloneOf the six patients treated with ciclosporin monotherapy, one had a CR with concurrent androgen therapy, two had a PR, one had a CR then relapsed and is now in PR on recommencement of ciclosporin, two had no response. There was no change in the granulocyte PNH clone following ciclosporin treatment. One patient proceeded to first line bone marrow transplantation (mean follow-up from presentation 7 months). Both BMT recipients stopped eculizumab post transplant due to resolution of PNH. Two patients died, one from infection following a PR with ATG and ciclosporin, and one from unknown causes who had not responded to treatment. One patient had spontaneous remission of their PNH and stopped eculizumab; the remaining nine patients continue on eculizumab.Fourteen age matched controls not on eculizumab received similar therapies, nine of whom received ATG and ciclosporin (median follow-up from ATG commencement 37 months). Four had a CR, one had a CR then relapsed with no response to re-introduction of ciclosporin, one had a PR and two had no response, one of whom had a BMT with CR and one achieved CR with oxymetholone. One ATG patient is awaiting response (four months post ATG). Five patients were treated with ciclosporin monotherapy (median follow-up from ciclosporin commencement 115 months). Two had a CR, one had a PR then relapsed, one had no response and achieved a PR with oxymetholone and one is awaiting response (three months post ciclosporin commencement).
Conclusion
Concurrent treatment of AA with IST and PNH with eculizumab has not previously been reported. 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 IST. Eculizumab therapy does not appear to affect response to IST for aplastic anaemia patients.This strategy may be required especially with improved life expectancy for PNH patients receiving complement inhibition therapy. The patients in this study were treated in accordance with current aplastic anaemia guidelines and the presence PNH should not influence this.
Session topic: E-poster
Keyword(s): Aplastic anemia, Immunosuppressive therapy, Paroxysmal nocturnal hemoglobinuria (PNH)
Abstract: E1481
Type: Eposter Presentation
Background
At least 50% of aplastic anaemia (AA) patients have a PNH clone. Many have a small proportion of PNH cells requiring monitoring alone whereas others may present with both significant aplasia as well as PNH. Concurrent treatment for AA and PNH may therefore be required.
Aims
This retrospective analysis assess's the outcome of patients with concurrent PNH and aplastic anaemia who require complement blockade with eculizumab alongside immunosuppressive therapy (IST) for AA
Methods
The PNH National Service database (Leeds) was reviewed retrospectively. Patients who commenced eculizumab within a year of their aplastic anaemia treatment, or those treated for aplasia who were already established on eculizumab were selected.
Results
Fourteen patients were treated with eculizumab and immunosuppressive therapy concurrently. Median age was 38.5 years (range 7-76). AA treatment varied as per national guidelines dependant on the patient’s age, patient choice and co-morbidities. Seven out of fourteen received ATG and ciclosporin (median follow-up 20 months post ATG), six received ciclosporin monotherapy (median follow-up from commencement of ciclosporin 97 months). 6 of the 7 patients receiving ATG+Ciclosporin responded, two achieved complete response (CR) and four a partial response (PR), one of whom required tacrolimus and subsequently achieved a CR with androgen therapy and one who achieved PR with oxymetholone. One did not respond and achieved a CR with a bone marrow transplant (BMT). Median granulocyte count reduced from 88% to 50% post ATG treatment however there was no change in the monocyte PNH cloneOf the six patients treated with ciclosporin monotherapy, one had a CR with concurrent androgen therapy, two had a PR, one had a CR then relapsed and is now in PR on recommencement of ciclosporin, two had no response. There was no change in the granulocyte PNH clone following ciclosporin treatment. One patient proceeded to first line bone marrow transplantation (mean follow-up from presentation 7 months). Both BMT recipients stopped eculizumab post transplant due to resolution of PNH. Two patients died, one from infection following a PR with ATG and ciclosporin, and one from unknown causes who had not responded to treatment. One patient had spontaneous remission of their PNH and stopped eculizumab; the remaining nine patients continue on eculizumab.Fourteen age matched controls not on eculizumab received similar therapies, nine of whom received ATG and ciclosporin (median follow-up from ATG commencement 37 months). Four had a CR, one had a CR then relapsed with no response to re-introduction of ciclosporin, one had a PR and two had no response, one of whom had a BMT with CR and one achieved CR with oxymetholone. One ATG patient is awaiting response (four months post ATG). Five patients were treated with ciclosporin monotherapy (median follow-up from ciclosporin commencement 115 months). Two had a CR, one had a PR then relapsed, one had no response and achieved a PR with oxymetholone and one is awaiting response (three months post ciclosporin commencement).
Conclusion
Concurrent treatment of AA with IST and PNH with eculizumab has not previously been reported. 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 IST. Eculizumab therapy does not appear to affect response to IST for aplastic anaemia patients.This strategy may be required especially with improved life expectancy for PNH patients receiving complement inhibition therapy. The patients in this study were treated in accordance with current aplastic anaemia guidelines and the presence PNH should not influence this.
Session topic: E-poster
Keyword(s): Aplastic anemia, Immunosuppressive therapy, Paroxysmal nocturnal hemoglobinuria (PNH)
Type: Eposter Presentation
Background
At least 50% of aplastic anaemia (AA) patients have a PNH clone. Many have a small proportion of PNH cells requiring monitoring alone whereas others may present with both significant aplasia as well as PNH. Concurrent treatment for AA and PNH may therefore be required.
Aims
This retrospective analysis assess's the outcome of patients with concurrent PNH and aplastic anaemia who require complement blockade with eculizumab alongside immunosuppressive therapy (IST) for AA
Methods
The PNH National Service database (Leeds) was reviewed retrospectively. Patients who commenced eculizumab within a year of their aplastic anaemia treatment, or those treated for aplasia who were already established on eculizumab were selected.
Results
Fourteen patients were treated with eculizumab and immunosuppressive therapy concurrently. Median age was 38.5 years (range 7-76). AA treatment varied as per national guidelines dependant on the patient’s age, patient choice and co-morbidities. Seven out of fourteen received ATG and ciclosporin (median follow-up 20 months post ATG), six received ciclosporin monotherapy (median follow-up from commencement of ciclosporin 97 months). 6 of the 7 patients receiving ATG+Ciclosporin responded, two achieved complete response (CR) and four a partial response (PR), one of whom required tacrolimus and subsequently achieved a CR with androgen therapy and one who achieved PR with oxymetholone. One did not respond and achieved a CR with a bone marrow transplant (BMT). Median granulocyte count reduced from 88% to 50% post ATG treatment however there was no change in the monocyte PNH cloneOf the six patients treated with ciclosporin monotherapy, one had a CR with concurrent androgen therapy, two had a PR, one had a CR then relapsed and is now in PR on recommencement of ciclosporin, two had no response. There was no change in the granulocyte PNH clone following ciclosporin treatment. One patient proceeded to first line bone marrow transplantation (mean follow-up from presentation 7 months). Both BMT recipients stopped eculizumab post transplant due to resolution of PNH. Two patients died, one from infection following a PR with ATG and ciclosporin, and one from unknown causes who had not responded to treatment. One patient had spontaneous remission of their PNH and stopped eculizumab; the remaining nine patients continue on eculizumab.Fourteen age matched controls not on eculizumab received similar therapies, nine of whom received ATG and ciclosporin (median follow-up from ATG commencement 37 months). Four had a CR, one had a CR then relapsed with no response to re-introduction of ciclosporin, one had a PR and two had no response, one of whom had a BMT with CR and one achieved CR with oxymetholone. One ATG patient is awaiting response (four months post ATG). Five patients were treated with ciclosporin monotherapy (median follow-up from ciclosporin commencement 115 months). Two had a CR, one had a PR then relapsed, one had no response and achieved a PR with oxymetholone and one is awaiting response (three months post ciclosporin commencement).
Conclusion
Concurrent treatment of AA with IST and PNH with eculizumab has not previously been reported. 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 IST. Eculizumab therapy does not appear to affect response to IST for aplastic anaemia patients.This strategy may be required especially with improved life expectancy for PNH patients receiving complement inhibition therapy. The patients in this study were treated in accordance with current aplastic anaemia guidelines and the presence PNH should not influence this.
Session topic: E-poster
Keyword(s): Aplastic anemia, Immunosuppressive therapy, Paroxysmal nocturnal hemoglobinuria (PNH)
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