Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity. METHODS: A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT. RESULTS: The median age at transplant was 11.0 months (4.6-61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ±â€¯17.9% (40-100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2-13.6), 0.9 × 109/L 0.6-1.2), and 0.5 × 109/L (0.2-0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0-14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4-11.5). The 10-year overall probability of survival is 84.3%. CONCLUSION: Monitoring IRC is important in ensuring adequate disease-free survival.

Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study.

PURPOSE: The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). METHODS: Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n = 19) or normal saline placebo (n = 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. RESULTS: At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. CONCLUSIONS: Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Genetic Causes, Clinical Features, and Survival of Underlying Inborn Errors of Immunity in Omani Patients: a Single-Center Study.

PURPOSE: Early identification of inborn errors of immunity (IEIs) is crucial due to the significant risk of morbidity and mortality. This study aimed to describe the genetic causes, clinical features, and survival rate of IEIs in Omani patients. METHODS: A prospective study of all Omani patients evaluated for immunodeficiency was conducted over a 17-year period. Clinical features and diagnostic immunological findings were recorded. Targeted gene testing was performed in cases of obvious immunodeficiency. For cases with less conclusive phenotypes, a gene panel was performed, followed by whole-exome sequencing if necessary. RESULTS: A total of 185 patients were diagnosed with IEIs during the study period; of these, 60.5% were male. Mean ages at symptom onset and diagnosis were 30.0 and 50.5 months, respectively. Consanguinity and a family history of IEIs were present in 86.9% and 50.8%, respectively. Most patients presented with lower respiratory infections (65.9%), followed by growth and development manifestations (43.2%). Phagocytic defects were the most common cause of IEIs (31.9%), followed by combined immunodeficiency (21.1%). Overall, 109 of 132 patients (82.6%) who underwent genetic testing received a genetic diagnosis, while testing was inconclusive for the remaining 23 patients (17.4%). Among patients with established diagnoses, 37 genes and 44 variants were identified. Autosomal recessive inheritance was present in 81.7% of patients with gene defects. Several variants were novel. Intravenous immunoglobulin therapy was administered to 39.4% of patients and 21.6% received hematopoietic stem cell transplantation. The overall survival rate was 75.1%. CONCLUSION: This study highlights the genetic causes of IEIs in Omani patients. This information may help in the early identification and management of the disease, thereby improving survival and quality of life.

Cytomegalovirus Infection Post-hematopoietic Stem Cell Transplant: Incidence, Risk Factors, and Outcome in an Omani Cohort.

Objectives: To estimate the incidence, risk factors, and outcome of cytomegalovirus (CMV) infection during the first year following hematopoietic stem cell transplant (HSCT) among Omani patients. Methods: This retrospective study included allogenic HSCT recipients between January 2006 and December 2018. We investigated the possible factors associated with CMV infection and CMV impact on one-year mortality. Results: Among 556 recipients of allogenic HSCT, 308 (55.4%) were male, the median age was 12 years, and 366 (65.8%) had benign conditions. One-year after transplants, the prevalence of CMV infection was 59.4%, and that of CMV disease was 1.8%. Multivariate analyses revealed significant relationships between CMV infection and haploidentical transplant (p = 0.006), graft versus host disease (p = 0.013), myeloablative conditioning (p = 0.001), and patient age ≥ 12 years (p < 0.001). CMV infection was associated with an increased risk of one-year mortality (p = 0.001). One-year overall mortality was 8.3%. Conclusions: The incidence of CMV infection in this Omani cohort was comparable with earlier findings, but the disease incidence and overall mortality were lower. Older age, haploidentical transplant, myeloablative conditioning, and graft versus host disease were significantly associated with a higher risk of CMV infection. In addition, CMV infection was associated with an increased risk of overall mortality in the first year post-transplant. Our findings support early initiation of preemptive therapy at low-level CMV viremia.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT. METHODS: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes. RESULTS: A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively). CONCLUSIONS: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Pigmented Villonodular Synovitis as an Atypical Cause of Deep Motor Branch Neuropathy.

OBJECTIVES: Compression of the ulnar nerve in Guyon's canal results in ulnar tunnel syndrome (UTS). The patient may present with sensory and motor deficits (zone 1), motor deficit (zone 2), or sensory deficit (zone 3). The most common causes of UTS include ganglion cysts, idiopathic ulnar nerve compression, occupational pressure neuritis (repetitive compression), prolonged compression, hook of hamate fractures, and arterial thrombus or aneurysm. CASE REPORT: We report an atypical cause of UTS involving pigmented villonodular synovitis (PVNS) with a review of the literature. Surgical decompression of the ulnar nerve at Guyon's canal has resulted in resolving motor weakness and improved interosseous strength at latest follow-up. CONCLUSION: The most common causes of UTS are ganglion, occupational neuritis, prolonged compression, and ulnar artery thrombi/aneurysms. However, other more rare causes such as PVNS should be considered in the appropriate patient.

Hematopoietic Stem Cell Transplantation for Patients with Autosomal Recessive Complete INF-λ Receptor 2 Deficiency: Experience in Oman.

Autosomal recessive complete INF-γ receptor-2 (IFN-γR2) deficiency is a rare, potentially fatal primary immune deficiency that predisposes to disseminated mycobacterial disease. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment. Few patients have been reported so far. Here we report the outcomes of HSCT in 7 patients with IFNγ-R2 deficiency from 3 Omani families who underwent HSCT at Sultan Qaboos University Hospital in Oman. All patients were homozygous for the same mutation (c.-175_+102del) of INFGR2. Four patients underwent HLA-matched related donor (MRD) HSCT (3 siblings and 1 parent), and the other 3 underwent T cell-depleted (TCD) haploidentical HSCT from a family donor. The stem cell source was peripheral blood stem cells in 5 patients and bone marrow in 2 patients. Five patients received myeloablative conditioning, and 2 had reduced-intensity conditioning. The overall survival rate was 85.7%, and the event-free survival was 71.4%. One of the 7 patients died on day +31 with gram-negative sepsis, and the other 6 patients were cured from their original disease (median follow-up of 78.5 months). One patient had primary graft failure following a TCD-haploidentical transplantation and underwent successful retransplantation from another haploidentical relative. Three patients received a donor lymphocyte infusion for mixed chimerism. Our findings indicate that HSCT is curative for complete IFN-γR2 deficiency. In this cohort from Oman, 85.7% of the patients were cured with either an MRD or a TCD haploidentical transplantation. Genetic analysis at birth in children of high-risk couples permits early diagnosis, prevents the morbidity of BCG vaccination, and can enable safer and more successful transplantation outcomes.

Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800-900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration-time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.

T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation for Patients with Familial Hemophagocytic Lymphohistiocytosis Who Do Not Have Matched Family Donors: Experience in Oman.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a potentially fatal disorder of immune regulation. Management includes chemotherapy followed by hematopoietic stem cell transplantation (HSCT). T cell depleted (TCD)-haploidentical HSCT could be an option for those patients who do not have HLA matching family donor. The objective of this study was to report on the outcome of TCD-haploidentical HSCT in patients with FHLH who underwent transplantation at Sultan Qaboos University Hospital (SQUH). This is a retrospective report on 12 patients with FHLH who received TCD- haploidentical HSCT at SQUH between August 2010 and December 2018. Epidemiologic characteristics and details on the transplantation procedures and complications were collected from patients' electronic records. Twelve patients with FHLH received TCD-haploidentical HSCT after a myeloablative conditioning regimen composed of treosulfan/thiotepa/fludarabine/anti-thymocyte globulin and rituximab. The mean age at transplantation was 11.67 ± 8 months. All patients had Perforin gene mutations, except 1 patient who had an UNC-13D mutation. Most patients received TCRαß+/CD19+ depleted grafts for faster immune reconstitution. Seven patients (58.3%) have been cured with a mean follow-up duration of 3.44 years. Four patients died of multiorgan failure secondary to gram-negative sepsis. One patient had primary graft failure, and 2 patients had mild graft-versus-host disease. Two patients had Pneumocystis carinii pneumonia, 2 had adenoviremia, and 9 patients had cytomegalovirus (CMV) viremia. Among patients with CMV viremia, 2 had evidence of disease (retinitis, enteritis). All patients with CMV viremia were treated successfully with foscarnet pre-engraftment and ganciclovir postengraftment, respectively. TCD-haploidentical HSCT could be a viable option for patients with FHLH who do not have HLA matching family donors. Infectious complications are the leading cause of death in that setting. CMV viremia was the most frequently encountered infectious complication.

Efficiency of day 4 compared to day 6 stem cell mobilization in allogeneic stem cell donors.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) given for 4-6 days is commonly used for mobilization of allogeneic stem cell donors. The primary objective of this study is to compare the yield of stem cell mobilization, assessed using a surrogate endpoint of CD34+ cell count, between Day 4 and Day 6. STUDY DESIGN AND METHODS: In this retrospective study we included all allogeneic stem cell donors mobilized with G-CSF for 6 days from January 2003 until October 2015 in the bone marrow transplantation unit at a tertiary academic center. Of 106 donor records reviewed, 84 were with available data and selected for the study. RESULTS: We included 84 donors with median age and weight of 19 years and 60 kg respectively. The median Day 4 WBC and CD34+ cell count were 37.4 × 109/L and 54 × 106/L respectively; while the median Day 6 WBC and CD34+ cell count were 44.4 × 109/L and 86 × 106/L respectively with a statistically significant difference from Day 4 (P < 0.001). In the multivariable model, there were no significant impact of donor's age (P = 0.215), weight (P = 0.108), height (P = 0.428) and mean corpuscular volume (P = 0.263) on the difference in CD34+ cell yield. However, the donor's blood group AB predicated a significantly higher difference (P = 0.036). CONCLUSION: Six days of G-CSF mobilization achieves higher CD34+ cell count than 4 days in allogeneic stem cell donors especially in donors with blood group AB, albeit both approaches give count higher than the successful collection threshold.

Early Versus Late Motion Following Volar Plating of Distal Radius Fractures.

Background: Distal radius fractures are common, and the trend in fixation has included the use of locked volar plating. The duration of splinting required after surgery and the effect splinting has upon outcome of the wrist are not clear. Our aim was to compare outcome of patients treated with early versus late motion protocol after volar plating. Methods: Thirty-three patients with distal radius fractures were prospectively and randomly enrolled into an early versus late motion study including volar plating of the distal radius fracture. Early motion included an active and passive wrist motion protocol by 14 days after surgery and delayed motion was initiated at 5 weeks. Fractures were defined as intra-articular and extra-articular, and those with, and without, ulnar styloid fracture. Motion and outcome scores (Disabilities of the Arm, Shoulder and Hand [DASH]/patient-rated wrist evaluation [PRWE]), and strength were measured through 1 year. Results: Wrist motion, DASH, and PRWE scores were only significantly different at 6 weeks with no significant differences at any later time points up to 1 year. One patient had complex regional pain syndrome (CRPS) and one had adhesive capsulitis in the late motion group. Conclusions: Following locked volar plating of distal radius fractures, early motion favored earlier return of motion along with lower DASH, PRWE, and pain scores within first 6 weeks. Although the late motion group had delayed recovery, there were no long-term significant differences in motion, strength, outcome, or pain scores. The 2 cases with complications (CRPS and adhesive capsulitis) did occur in the late motion group and may implicate late motion with these problems.

Impact of Home-to-Centre Distance on Bone Marrow Transplantation Outcomes.

OBJECTIVES: Haematopoietic stem cell transplantation (HSCT) in Oman started in 1994 at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Previous studies have suggested that longer driving time to the transplant centre (DTC) independently correlates with worse overall survival (OS). Therefore, this study aimed to examine the impact of DTC on OS and acute graft-versus-host disease (aGvHD). METHODS: This retrospective study included all patients who underwent HSCT between February 2006 and December 2016 at SQUH. The DTC was determined using Google Maps (Google LLC., Mountain View, California, USA). The probability of OS was estimated using a Kaplan-Meier estimator and the impact of DTC on OS was compared using a Cox model. RESULTS: A total of 170 patients were included in this study of which 52% were male and 28% were from the Al Batinah region. The mean age was 14.2 ± 12.2 years. The mean haemoglobin, platelet and white blood cell counts before the HSCT were 10.3 ± 1.7 g/dL, 207 ± 131 × 109/L and 5.1 ± 5.9 × 109/L, respectively. The median DTC for those with aGvHD was 84 minutes, which is similar to patients without aGvHD (P = 0.918). The hazard ratio for DTC as a predictor of OS was 1.0 (P = 0.901). CONCLUSION: In this single centre study, DTC did not impact aGvHD or OS in patients post-HSCT. The study was limited by its retrospective design and the small sample size. It is recommended that these results be confirmed in a prospective study.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients.

Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15years (range 2-55years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39mg/day with a statistically significant difference (p<0.001) even after adjusting for the weight (median total FBD of 349mg, median TDM dose of 494mg, p<0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p<0.001 and p<0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture.

Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care Hospital.

PURPOSE: Primary immunodeficiency (PID) diseases are rare, complex medical disorders that often are overlooked in clinical settings. There are emerging reports of PID from Middle Eastern populations. This study describes the features of PID patients in a tertiary care setting in Oman and compares them with regional and worldwide reports. METHOD: Sultan Qaboos University Hospital (SQUH) is an academic tertiary care-level hospital for specialized healthcare, including PID patients. At the time of diagnosis, patients' sociodemographics, clinical features, laboratory investigations, and management were entered in electronic form. This study included patients seen between August 2005 and July 2015. RESULTS: One hundred forty patients were registered with a minimum estimated population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median age of onset of symptoms was 8 months, and diagnosis was 21 months with a delay of 13 months. Family history was positive in 44 %, consanguinity was present in 76 %, death of a previous sibling was present in 36 %, and there was an overall mortality in 18 %, with an 85 % probability of survival 10 years following diagnosis. The most common type of immunodeficiency was phagocytic disorders (35.0 %), followed by predominantly antibody disorders (20.7 %), combined immunodeficiency (17.8 %), other well-defined PID syndromes (15.0 %), immune dysregulation syndromes (3.5 %), complement deficiencies (3.5 %), and unclassified immunodeficiency (4.2 %). The commonest presenting infection was pneumonia (47.1 %). CONCLUSION: PID is not a rare condition in Oman. The prevalence is in concordance with reports from the region but higher than in Western populations. The findings of the current study would help to improve the awareness and management of, and policy making for PID.

Hematopoietic stem cell transplantation in the Eastern Mediterranean Region (EMRO) 2011-2012: A comprehensive report on behalf of the Eastern Mediterranean Blood and Marrow Transplantation group (EMBMT).

OBJECTIVE/BACKGROUND: The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group has accumulated over 31 years of data and experience in hematopoietic stem cell transplantation (HSCT), particularly in hemoglobinopathies, severe aplastic anemia, inherited metabolic and immune disorders, in addition to a wide array of hematologic malignancies unique to this region. A regional update in current HSCT trends is highly warranted. We studied the trends of HSCT activities in World Health Organization-Eastern Mediterranean (EMRO) region, surveyed by the EMBMT, between 2011 and 2012. METHODS: Retrospective analysis of the survey data mainly of cumulative number of transplants, types of transplants (autologous vs. allogeneic), types of conditioning such as myeloablative versus reduced intensity was conducted. Also, trends in leukemias, hemoglobinopathies, severe aplastic anemia, inherited bone marrow failure syndromes, amongst others were analyzed. RESULTS: Twenty-one teams from nine EMRO countries reported their data (100% return rate) to the EMBMT for the years 2011-2012, with a total of 3,546 first HSCT (1,670 in 2011; 1,876 in 2012). Allogeneic HSCT (allo-HSCT) represented the majority (62%) in both years. The main indications for allo-HSCT were acute leukemias (988; 46%), bone marrow failure syndromes (421, 20%), hemoglobinopathies (242; 11%), and immune deficiencies (157; 7%). There was a progressive increase in the proportions of chronic myeloid leukemia cases transplanted beyond first chronic phase (37 [7%] of all chronic myeloid leukemia cases in 2011 vs. 39 [29%] in 2012). The main indications for autologous transplants were multiple myeloma/plasma cell disorders (510; 39%), Hodgkin lymphoma (311; 24%), non-Hodgkin lymphoma (259; 20%), and solid tumors (163; 12%). Reduced intensity conditioning continued to show a progressive decrease over years (9.5% in 2011 vs. 7.9% in 2012), yet remained relatively low compared with contemporary practices in Europe published by EBMT. The vast majority (91%) of allo-HSCT source was from sibling donors with continued dominance of peripheral blood (64%) followed by bone marrow (33%).While umbilical cord blood transplants increased to 4% of allo-HSCT, matched unrelated donor remained underutilized and there was no haplo-identical transplant reported. Large centers with >50 HSCT/year, showed a continued increase in the total number of allo-HSCT over the past 2years that may be related to capacity building issues and require further studies. CONCLUSION: There is a discernable increase of HSCT rate in the EMRO region with a significant expansion in utilization of cord blood transplants and allogeneic peripheral blood-HSCT as a valuable source. However, further research of outcome data and the development of regional donor banks (cord blood and matched unrelated donors) may help to facilitate future planning to satisfy the escalating regional needs and augment collaboration within the EMBMT and globally.

Outcomes after radiocarpal dislocation: a retrospective review.

BACKGROUND: Radiocarpal dislocations are rare, high-energy injuries. High morbidity and poor functional outcomes are common. Currently, there is limited data on functional outcomes following treatment of this injury. METHODS: A retrospective review was conducted analyzing the radiographic and clinical outcome of patients treated for a radiocarpal dislocation from 1979 to 2010. Outcome assessments included wrist range of motion, grip strength, Mayo wrist score, patient-rated wrist evaluation (PRWE), and disabilities of the arm, shoulder and hand (DASH) score. Statistical analysis was performed with the Student's t test. RESULTS: Twenty-six patients (26 wrists) were treated for a radiocarpal dislocation during the study period; 23 wrists were treated acutely (within 4 weeks of injury), and 3 were treated after a delayed presentation (>4 weeks). Clinical follow-up of more than 6 months was available in 17 patients. Three patients (12 %) underwent primary fusion as initial treatment (two radioscapholunate fusion; one total wrist fusion). Four wrists (24 %) failed initial treatment and were salvaged with scapholunate ligament reconstruction (one wrist) or partial wrist fusion (three wrists). Seventeen patients completed PRWE and DASH questionnaires with a mean of 14.6 years following surgery (range 2-32 years). Subjective outcomes tended to be superior in those patients treated with ligament reconstruction versus partial or complete wrist fusion; however, comparisons were not statistically significant. CONCLUSION: Radiocarpal dislocations result in significant osseous and ligamentous injury to the distal radius and carpus. Early recognition and treatment of radiocarpal dislocations with open reduction, internal fixation, and repair of ligaments may result in improved long-term functional outcomes when compared to acute partial or complete wrist arthrodesis.

Chediak-Higashi syndrome: novel mutation of the CHS1/LYST gene in 3 Omani patients.

BACKGROUND: Chediak-Higashi syndrome (CHS) is a rare, autosomal, recessive lysosomal disorder with hematological and immunologic abnormalities; however, stem-cell transplantation from a matched or related donor may be curative. Many mutations of the CHS1/LYST gene have been reported to date. We report a novel nonsense mutation of the CHS1/LYST gene in 3 Omani patients. METHODS AND RESULTS: Three patients from 2 different families presented with clinical and laboratory features of CHS and a history of death of a previous sibling because of a severe illness, suggestive of the accelerated phase of CHS. Giant granules were present in the myeloid cell lines. Before the stem-cell transplant, the first patient underwent gene sequencing of all exons of the lysosome trafficking regulator (CHS1/LYST) gene and revealed a nonsense mutation in exon 5 (c.925C>T, p.R309X). Subsequently, upon presentation, the second and third patients' direct gene sequencing of exon 5 revealed the same mutation. CONCLUSIONS: We report a nonsense mutation in exon 5 (c.925C>T, p.R309X). This supports the allelic heterogeneity of CHS and is in line with most reported mutation types that lead to a truncated protein. Identification of the mutation type will facilitate timely diagnosis, management, and family counseling for those with affected children in Oman.