ABSTRACT
Background@#Reduced harvest volumes in pediatric donors appear to have the potential to reduce donor-associated risks while maintaining engraftment in recipients; however, the allowable harvest volume reduction remains undefined. @*Methods@#We retrospectively analyzed the data pairs of 553 bone marrow (BM) harvests from pediatric (age at harvest ＜18 yr) sibling donors and clinical outcomes of 553 pediatric (age at infusion ＜14 yr) transplant-naïve recipients to assess the optimal BM harvest volume needed from pediatric donors to obtain the desired CD34+ cell count (≥3.0×10 6 cells per kg of recipient weight), and to study its impact on the clinical outcomes of transplantation in pediatric recipients. @*Results@#The minimum desired CD34+ cell count of ≥3.0×10 6 per kg of recipient weight was achieved for 506 (95.3%) of donor-recipient pairs. The median CD34+ cell yield was 6.4×10 6 per kg of recipient weight (range, 1.2‒33.8×10 6 ) in donors younger than 5 years old at harvest, 4.7×10 6 (range, 0.3‒28.5×10 6 ) in donors aged 5‒10 years and 2.1×10 6 range, 0.3‒11.3×10 6 ) in donors older than 10 years (P ＜0.001). @*Conclusion@#The infused CD34+ cell dose (×10 6 cells/kg of recipient weight) had no impact on GRFS; however, a CD34+ cell dose of ＞7×10 6 cells/kg of recipient weight did not improve hematopoietic recovery
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Bone marrow failure syndrome is an epithet of bone marrow failure [all or single-cell lineage] that is attributable to an underlying genetic aberration usually with a constellation of somatic abnormalities. Multiple inheritance patterns have been described in these disorders; many are transmitted in an autosomal recessive pattern, which may consequently lead to a higher prevalence of such illnesses in homogeneous societies such as Saudi Arabia, where consanguineous marriages are not uncommon. At King Faisal Specialist Hospital and Research Center, the most common entity referred for allogeneic hematopoietic cell transplantation [HCT] is Fanconi anemia, followed by pure red aplasia, and, less commonly, dyskeratosis congenita, congenital neutropenia, and others. Of all the congenital bone marrow failure syndromes, two of them-Fanconi anemia and dyskeratosis congenital-represent a real challenge in terms of conditioning for HCT and require special attention. This minireview is a snapshot of the recent international and local experience of HCT in these two entities
ABSTRACT
To evaluate the efficacy of a 2-drug chemotherapy regimen without external-beam radiotherapy [EBRT] and/or without enucleation in bilateral retinoblastoma. From 1996 to 2010, 79 patients were diagnosed with bilateral RB and were eligible for chemotherapy. Chemotherapy was administered prior to and/or following local therapy to the eye. All patients received 3 cycles of chemo-reduction with carboplatin and vincristine, additional cycles of the same or other chemotherapy, local therapy, EBRT and enucleation were determined according to re-evaluation by the ophthalmologist. Advanced disease was seen in 115 [79%] eyes [group IV and V: 96, Group D and E: 19] out of 146 affected eyes. Tumor response after chemotherapy was observed in 78 patients [98.7%]; complete response in 25 [32.1%], partial response in 49 [62.8%] Four [5.1%] had progressive disease. A total of 50 [63.3%] patients required EBRT; 38 for persistent disease, 4 for progressive disease, 2 for new lesions, 2 for re-activation and 4 for disease control. Enucleation was required in 15 [19%]. Secondary malignancies occurred in two patients who underwent EBRT; one osteogenic sarcoma and one rhabdomyosarcoma then later osteogenic sarcoma. The 10 year overall survival was 96.3% with a median follow-up time of 3.124 +/- 0.536 years [95%CI: 2.074-4.174]. The 2-drug chemotherapy regimen combined with local therapy appears to be adequate therapy for low stage disease but not in patients with advanced disease. The occurrence of secondary cancers in this group of patients is worrisome further highlighting the deleterious effects of EBRT
ABSTRACT
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
ABSTRACT
Stem cells from umbilical cord blood [CB] have increasingly become a viable alternate source of progenitor cells for hematopoietic cell transplantation [HSCT] Cytomegalovirus [CMV] is thought to contribute significantly to HSCT morbidity and mortality. Retrospective case-control study in patients at tertiary care center. We determined the incidence, risk factors and outcomes for CMV infection and disease after unrelated cord blood transplantation [UCBT] in children. Between 2003 and 2007, 73 pediatric patients underwent UCBT and 68% of recipients were CMV seropositive. The overall incidence of CMV infection, early and late CMV infection was 58.9% [43/73], 62.8% [27/43], and 37.4% [1 6/43], respectively. In patients with early CMV infection, 6 of 27 [22%] patients progressed to develop CMV end-organ disease including pneumonitis and retinitis. High levels CMV antigenemia >70 infected cells by pp65 antigenemia assay + PMNs, P-.237 were associated with a higher risk of progression to CMV disease. The development of CMV infections was higher in CMV-seropositive recipients [P<.001] and in those who developed graft-versus-host-diseases [GVHD] [P<.001]. Other risk factors for CMV infection include the use of high-dose corticosteroids [P<.001] and older age of the recipient at the time of transplant [P<.002]. Late CMV infection was strongly associated with a previous history of early CMV infection [P<.001]. CMV infection is a significant complication in UCBT recipients in pediatric patients and is associated with an increase in transplant-related morbidity and mortality. Risk factors for CMV infections after UCBT include GVHD, use of corticosteroids, underlying diseases [hematologic malignancies] and older age. Late CMV infection was strongly associated with a previous history of CMV infection
Subject(s)
Humans , Infant , Male , Female , Child , Cord Blood Stem Cell Transplantation , Incidence , Risk Factors , Retrospective Studies , Case-Control StudiesABSTRACT
Therapy for patients with congenital sideroblastic anemia has been limited to blood transfusions and chelation. Five patients with Congenital Sideroblastic anemia [CSA] who were blood transfusion dependent underwent stem cell transplantation [SCT] from matched sibling donors. Their ages at SCT were 1,2,3,5 and 8 years. Conditioning consisted of cyclophasphamide 50 mg/kg/day for 4 days, busulfan 4 mg/kg/day for days and antithymocyte globulin [ATG] 30 mg/kg/for 4 doses pretransplant. For Graft vs. Host disease [GVHD] prophylaxis, cyclosporin A and methotrexate were used. All patient engrafted, and are alive with sustained engraftment and are transfusion independent. Two patients developed acute GVHD, and none of the patients developed chronic GVHD. In conclusion SCT can be curative for patients with CSA