Outcomes Of Haematopoietic Stem Cell Transplantation (HSCT) for Severe Congenital Neutropenia (SCN): Preliminary Results

Haematopoietic stem cell transplantation (HSCT) is indicated in patients affected with severe congenital neutropenia (SCN) who transformed into myelodysplasia/acute myeloid leukemia or in low responders to granulocyte colony stimulating factor (G-CSF) therapy. The outcome of HSCT in SCN is not well known because the experience is based on single case report or on small series.

describe outcomes of HSCT in SCN patients in a large cohort using EBMT data base.

all patients registered in the EBMT data base affected with severe congenital neutropenia (severe neutropenia diagnosed early in life with bone marrow block at promyelocytes stage in the bone marrow and G-CSF dependency) were considered eligible for the study. Data regarding HSCT and outcome were extracted from the “general” EBMT registry, while data on the history of disease before HSCT, was collected through a specific CRF sent to all the participating centers. Here we report preliminary of this survey.

A total of 119 patients from 19 participating countries were considered eligible for the study; 66% of the eligibile patients originated from Western Europe and 34% from Eastern Europe and the Eastern Mediterranean area (Iran, Israel, Saudi Arabia,Turkey and Russia). Females were 51% of the cohort. Median age at diagnosis of neutropenia was 0.35 years (0-35.4y), while median age at first transplant was 4.8 years (range 0.2-43y). Four patients were affected with MDS at time of transplant. The cell source was bone marrow (BM) in 56%, peripheral blood (PB) in 26% and cord blood (CB) 18%. Fiftypercent of patients were engrated from a related and 50% from an unrelated donor. Conditioning regimen was myeloablative in 86% and at reduced intensity (RIC) in 14% of the cohort Engraftment was documented in 91%; 5% has no engraftment while 4% lost the engraftment for a total of 10 patients. Chimerism was assessed only in 30% of the patients. Six of the 10 patients who had graft failure died after first transplant. Four underwent a second HSCT and 2 are alive2 died (2 alive and 2 death).Overall 22 patients (18.5%) died while the remaining 97 were alive (81.5%). Causes of death were GVDH 23%, Infection 23%, organ failure 18% and “other causes” 27%. Nine percent of patients died because of relapse/progression of the disease. Transplant related mortality was assessed at 17% on the whole cohort. Acute GVDH grade 1-2 was documented in 31% grade 3-4 in 14% and no GVDH in 54%. The 5-year OS and EFS rate was respectively 77% and 70 % in the whole cohort. The 5-year OS according to HLA identical donor and matched unrelated was respectively 83% and 79% (p=0.99, log-rank). Also the OS according to source of cells (5-year OS: CB 85%, PB 79% and BM 62% was not significant (p =0.13). Likewise no significant difference was found in EFS (CB 85% BM 75% and PB 52% p =0.08). OS by age of patients (5-year OS: 82 % for patients aged 0-2y, 83 % for age 2-5 y, 83% for age 5-10 and 60% for subjects aged above 10y) (p=0.07) and by period of HSCT: (90% between 2008-2012, 75% between 2001-2007 and 64% before 2000) were again not significant. No difference was also seen in OS and EFS according to myeloablative conditioning regimen and RIC.

this preliminary analysis indicate that the 5-year survival in transplanted SCN patients is close to 80% with no difference between matched related and unrelated donor. TRM is still a not negligible and close to 17%. There is a trend towards a more favourable survival in patients younger than 5 years at time of transplant, in those transplanted with cord blood and after the year 2000.

Marsh:Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Dufour:Pfizer: Consultancy, Research Funding.