Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation

Abstract

Key Points• The outcome of HSCT in this large SCN cohort is acceptable.• Given the TRM, a careful selection of HSCT candidates should be undertaken.Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day 190) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken. (Blood. 2015;126(16):1885-1892 Medscape Continuing

Children with rare diseases of neutrophil granulocytes: from therapeutic orphans to pioneers of individualized medicine

“…Fioredda et al have recently analyzed clinical data from the European Society for Blood and Marrow Transplantation to assess the outcome of 136 patients with SCN after allogeneic stem cell transplantation (SCT). 10 Overall survival after 3 years was 82%, and transplant-related mortality was 17%. A multivariate analysis showed that transplants performed in more recent years, in patients ,10 years, and using fully-matched HLA donors, had a better outcome.…”

“…Although these results document that SCN patients can be cured by allogeneic SCT with increasingly better results, morbidity and mortality of this approach remain considerable and require that patients to whom a transplant is offered must be carefully selected. 10 Conflict-of-interest disclosure: The author declares no competing financial interests.…”

Old and new faces of neutropenia in children

“…Transplant related mortality was 17%, thus suggesting that this procedure should not be offered to patients who can be effectively and easily managed with standard doses of G-CSF (5 mg /kg/day or less). 34 Research on new therapies are limited by the lack of animal models recapitulating the human severe neutropenia phenotype. Recently, induced pluripotent stem cell (iPSC) lines from SCN subjects have been generated and might become a helpful tool to screen possible new drugs.…”

“…32 In patients poorly/non responding to G-CSF (i.e., requiring>10 mg/kg/day and > 20 mg/kg/day, respectively) or already transformed to MDS/AL, stem cell transplantation (SCT) is an indicated treatment option. [33][34] The outcome of SCT in 136 SCN patients was analyzed in a collaborative study from EBMT and SCETIDE. 34 The three year probability of OS and EFS were 82% and 71%, respectively.…”

“…[33][34] The outcome of SCT in 136 SCN patients was analyzed in a collaborative study from EBMT and SCETIDE. 34 The three year probability of OS and EFS were 82% and 71%, respectively. In multivariate analysis, factors associated to a better outcome were transplant before age 10 years from an HLA-matched, related or unrelated, donor.…”