Should We Hold the Point of allogeneic Hematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Haemoglobinuria in Eculizumab Era?

PNH is a rare haematological disorder due to the clonal expansion of abnormal haemotopoietic stem cells ,carrying a mutation in the PIG-A gene. Eculizumab ,as a humanised anti-complement component (C5), has proven highly effective in controlling intravascular haemolysis, and is expected to result in a remarkable improvement of survival. Should Eculizumab thus be offered as first treatment to all PNH patients? Allogeneic hematopoietic stem cell transplantation is still the only curative treatment for PNH by eradicating the abnormal PNH clone, leading to definitive survival improvement and QOL benefits.

Methods We assessed the long-term clinical and hematologic results in 13 PNH patients who received Allogeneic hematopoietic stem cell transplantation in our centre between Jan 2010 and Apr 2014. The patients were aged 13 to 54 (median 24 years). Eight donors were HLA -haploidentical and 5 were HLA-identical (3 siblings and 2 unrelated donors).

Results Eleven patients received a myeloablative conditioning consisting of busulfan and cyclophosphamide and 2 were given a reduced intensity conditioning consisting of fludarabine, busulfan and ALG (2 HLA-identical sibling donor). All patients achieved sustained engraftment with a median time of 11 days (range 11-26) to reach 0.5 ×10⁹/L neutrophils and 15 days (range 12-126) to reach 20 ×10⁹/L platelets. The overall cumulative incidence of grade II-IV acute GvHD was 15.4% and 2 patients showed limited chronic GvHD in evaluable 12 patients (cumulative incidence 16.7%).Transplant-related mortality for all patients was 15.4% (1 due to TMA and 1 due to severe pulmonary infection). As of Aug 1,2014, 11 patients are alive with complete hematologic recovery and no evidence of PNH following a median follow-up of 13 months. The 3-year Kaplan-Meier probability of disease-free survival was 80.2±12.8%. No thromboembolic event nor recurrence of the disease were reported following transplant.

Conclusions The findings of this study confirm that most patients with PNH may be definitively cured with allogeneic hematopoietic stem cell transplantation.