Résumé
Background@#Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients. @*Methods@#FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed. @*Results@#Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P =0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001). @*Conclusion@#Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.
Résumé
Background@#Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients. @*Methods@#FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed. @*Results@#Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P =0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001). @*Conclusion@#Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.
Résumé
Allogeneic stem cell transplantation [SCT] offers the best chance of cure and long-term survival for children with myelodysplastic syndromes [MDS]. Retrospective analysis of pediatric patients with primary MDS treated with allogeneic SCT at a single institution treated between January 1993 and December 2008. Of 16 consecutive children who received allogeneic SCT for treatment of MDS in our center, 14 patients met the criteria of MDS according WHO I and II criteria. The median age was 4.8 years [range, 1-14 years] and 64% were male. The median time from diagnosis to transplant was 6 months. MDS stage was refractory cytopenia [RC] in 9, refractory anemia with excess blasts [RAEB] in 5. Monosomy 7 was present in 35% of the patients. The majority of patients [11/14] were conditioned with a busulfan-based myeloablative [MA] regimen with addition of low-dose of etoposide [30 mg/kg]. All but one received a bone marrow graft. Nine patients achieved complete remission [CR], and seven remain alive. At a median follow-up of 3 years [range, 2-14 years] the OS and EFS was 57% [95%CI, 0.28-0.78]. Cumulative EFS at 10 years was 43% [95% CI: 0.14-0.70]. Relapse-related mortality was 21.4%; nonrelapse mortality [NRM] was 28.57%. All the survivors had etoposide in their conditioning regimen. Patients younger than 10 years had better survival [P=.001]. Children with MDS achieve encouraging OS and EFS following allogeneic SCT. A busulfan-based regimen with a lower dose of etoposide is an effective and less toxic regimen. The outcomes are best in younger patients