Contributions
Abstract: PB1794
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
TA-TMA is a rare complication of HSCT that remains difficult to address due its significant morbimortality, lack of standard diagnostic criteria and limited therapeutic options. It is caused by endothelial injury and complement activation. It is further more common after allo-HSCT. Higher risk is in those patients with calcineurin inhibitors (CI), high dose chemotherapy or radiation, infections,GvHD, HLA mismatch or mutations in the complement system. Gold standard for diagnosis is the biopsy of the affected organ, but in the last years laboratory and clinical criteria were also developed. Kidneys, lungs and gastrointestinal tract are the most common affected organs. First-line management includes withdrawal of the CI, treatment of co-existing infections and GvHD and hypertension control. There are no clear recommendations about optimal specific treatment. Eculizumab, though off-label, is one of the most used drugs due to the promising results reported by various studies.
Aims
To evaluate the characteristics and results of the patients diagnosed of TA-TMA and treated with eculizumab in our centre.
Methods
Case reports of patients diagnosed of TA-TMA and treated with eculizumab in our centre between 2018 and 2019.
Results
Case reports of 7 patients. Most of them women (4). Age 51.9±11.7 years old. All caucasic. Indications for transplant: lymphoma (3), MDS (2) and leukemia (2). All of them allo-HSCT with MTX and TCR as GvHD prophylaxis. 5 donors were unrelated (4 10/10, 1 9/10) and 2 were related with HLAid. Day at diagnosis: 162.8±154.4. Most common affected organs: kidneys (4) and CNS (3). All had trombocytopenia, high LDH and anemia at diagnosis; >1% squistocytes (9), proteinuria (6) and hypertension (6). Biopsy was not performed. Mutations and C5b-C9 levels were not studied. Anti-factor H antibodies and ADAMTS13 levels were normal. Almost all the patients (6) had concomitant GvHD or infection (8). First-line treatment was withdrawal of TCR and control of the co-existing conditions; 1 patient received TPE and 2 rituximab prior eculizumab. Eculizumab was initiated 9.9±9.3 days after TA-TMA diagnosis. Almost half of the patients (3) reached CR after induction therapy (6 doses), but only 2 are still alive. Most common cause of exitus was septic shock.
Conclusion
As previously reported cases, all of our patients treated with eculizumab underwent allogeneic HSCT and received a calcineurin inhibitor as prophylaxis for GVHD. Affected organs and laboratory findings also correlated with previous literature. None of them responded to withdrawal of tacrolimus and most of them had concomitant infection or GvHD, which are known adverse risk factors. Begin of the disorder in our patients was later than common and less than a half happened before day 100 after the transplant. Following protocols in our centre we used TPE or rituximab while waiting for eculizumab approval in our centre. Similar to previous reports, 71% of patients reached complete response after its initiation and those who did not often died because of infection complications. However, given the small amount of patients, further studies with alleatory design are required to recommend eculizumab as an effective therapy of TA-TMA that not respond to supportive treatment and to evaluate the associated risks and prognostic factors.
Keyword(s): Bone marrow transplant, Complement, Thrombotic microangiopathy, Treatment
Abstract: PB1794
Type: Publication Only
Session title: Stem cell transplantation - Clinical
Background
TA-TMA is a rare complication of HSCT that remains difficult to address due its significant morbimortality, lack of standard diagnostic criteria and limited therapeutic options. It is caused by endothelial injury and complement activation. It is further more common after allo-HSCT. Higher risk is in those patients with calcineurin inhibitors (CI), high dose chemotherapy or radiation, infections,GvHD, HLA mismatch or mutations in the complement system. Gold standard for diagnosis is the biopsy of the affected organ, but in the last years laboratory and clinical criteria were also developed. Kidneys, lungs and gastrointestinal tract are the most common affected organs. First-line management includes withdrawal of the CI, treatment of co-existing infections and GvHD and hypertension control. There are no clear recommendations about optimal specific treatment. Eculizumab, though off-label, is one of the most used drugs due to the promising results reported by various studies.
Aims
To evaluate the characteristics and results of the patients diagnosed of TA-TMA and treated with eculizumab in our centre.
Methods
Case reports of patients diagnosed of TA-TMA and treated with eculizumab in our centre between 2018 and 2019.
Results
Case reports of 7 patients. Most of them women (4). Age 51.9±11.7 years old. All caucasic. Indications for transplant: lymphoma (3), MDS (2) and leukemia (2). All of them allo-HSCT with MTX and TCR as GvHD prophylaxis. 5 donors were unrelated (4 10/10, 1 9/10) and 2 were related with HLAid. Day at diagnosis: 162.8±154.4. Most common affected organs: kidneys (4) and CNS (3). All had trombocytopenia, high LDH and anemia at diagnosis; >1% squistocytes (9), proteinuria (6) and hypertension (6). Biopsy was not performed. Mutations and C5b-C9 levels were not studied. Anti-factor H antibodies and ADAMTS13 levels were normal. Almost all the patients (6) had concomitant GvHD or infection (8). First-line treatment was withdrawal of TCR and control of the co-existing conditions; 1 patient received TPE and 2 rituximab prior eculizumab. Eculizumab was initiated 9.9±9.3 days after TA-TMA diagnosis. Almost half of the patients (3) reached CR after induction therapy (6 doses), but only 2 are still alive. Most common cause of exitus was septic shock.
Conclusion
As previously reported cases, all of our patients treated with eculizumab underwent allogeneic HSCT and received a calcineurin inhibitor as prophylaxis for GVHD. Affected organs and laboratory findings also correlated with previous literature. None of them responded to withdrawal of tacrolimus and most of them had concomitant infection or GvHD, which are known adverse risk factors. Begin of the disorder in our patients was later than common and less than a half happened before day 100 after the transplant. Following protocols in our centre we used TPE or rituximab while waiting for eculizumab approval in our centre. Similar to previous reports, 71% of patients reached complete response after its initiation and those who did not often died because of infection complications. However, given the small amount of patients, further studies with alleatory design are required to recommend eculizumab as an effective therapy of TA-TMA that not respond to supportive treatment and to evaluate the associated risks and prognostic factors.
Keyword(s): Bone marrow transplant, Complement, Thrombotic microangiopathy, Treatment