Allogeneic transplants not recommended for PNH-related thromboembolism

Issue: July 25, 2012

Stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria did not result in increased survival, according to results of a retrospective, multicenter study.

Perspective from Robert A. Brodsky, MD

Although stem cell transplantation is the only curative treatment for paroxysmal nocturnal hemoglobinuria (PNH), the treatment is associated with a high mortality rate, according to background information in the study. Therefore, transplantation normally is deferred until disease progression or life-threatening thromboembolism. In addition, treatment with eculizumab (Soliris, Alexion) has been found to significantly reduce the risk of thromboembolism, calling into question the utility of stem cell transplantations in the current era.

In this study, researchers examined outcomes after stem cell transplantation in a group of 211 patients with PNH from 1978 to 2007. This group was matched with 402 patients with PNH who had complications from the disease such as thromboembolism or aplastic anemia.

According to the results, 14 of 202 patients did not engraft and 85 developed acute graft-versus-host disease. At 61 months follow-up, 64 of these patients had died. Researchers calculated the probability of survival at 5 years to be 68%; however, they were unable to identify any transplant outcome as having a statistically significant association with survival.

When looking at patients by the reason for undergoing transplantation, the researchers found that the OS was 54% in patients with thromboembolism. When this group of patients was compared with matched controls of non-transplanted patients with thromboembolism, the data indicated that transplanted patients had a worse OS (HR=10.0; P=.007).

Five-year OS was 69% in patients with aplastic anemia without thromboembolism. Compared with a group of matched non-transplanted patients, those patients with aplastic anemia who underwent transplantation did not have significantly worse OS (HR=4.0; P=.06).

Five-year OS was 86% in patients with recurrent hemolytic anemia without thromboembolism or aplastic anemia.

“In conclusion, given our present results, and the efficacy of eculizumab, the current indications for stem cell transplantation should be challenged,” the researchers wrote. “Stem cell transplantation cannot be considered any longer as the standard of care of PNH patients with thromboembolism when eculizumab is available.”

Reference:

de LaTour RP. Haematologica. 2012;doi:10.3324/haematol.2012.062828.

Perspective

Robert A. Brodsky, MD

This retrospective registry-based study attempts to address the difficult question of who, if anyone, with PNH should receive an allogeneic bone marrow transplant in the era of terminal complement inhibition. Based on their analysis of more than 200 PNH patients who were transplanted at 83 centers between 1978 and 2007, the researchers concluded that allogeneic bone marrow transplantation is probably not a suitable treatment option for PNH, especially those with life-threatening thromboembolism. Although their conclusions are probably valid for most patients, it is important to recognize that BMT remains the only curative option for PNH and that eculizumab costs almost $400,000 per patient per year. Most of the patients in this study received myeloablative conditioning (not necessary for PNH) and were transplanted more than a decade ago. Infections and graft-versus-host disease were the leading causes of death. Newer non-myeloablative regimens, better HLA-typing and better graft-versus-host disease prophylaxis — such as post-transplant cyclophosphamide — are leading to markedly improved outcomes after bone marrow transplantation. Furthermore, there are rare PNH patients who have suboptimal responses to eculizumab. In short, bone marrow transplantation should probably not be offered to most PNH patients; however, for patients with suboptimal responses to eculizumab, bone marrow transplantation may still be reasonable.

Robert A. Brodsky, MD

Director, division of hematology

The Johns Hopkins Hospital

Disclosures: Dr. Brodsky reports no relevant financial disclosures.