A Multicenter Retrospective Analysis Stressing the Importance of Long-Term Follow-Up after Hematopoietic Cell Transplantation for ß-Thalassemia.

Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with ß-thalassemia major. However, most reports on HCT outcomes lack long-term follow-up data with the exception of single-center reports. An international multicenter retrospective data collection and analysis was conducted in 176 ß-thalassemia patients who were 1 year or beyond after first HCT to evaluate follow-up methods and outcomes at 7 centers. Median age at HCT was 5.5 years (range, .6 to 18.5), and median follow-up was 7 years (range, 1 to 20). HCT was predominantly from HLA-matched related donors (91%) with bone marrow as stem cell source (91%) and myeloablative conditioning regimens (88%). Late mortality or persistent chronic graft-versus-host disease (GVHD) was rare (<2%). Graft rejection was reported in 23% (24% of these occurred beyond 1 year) post-HCT. Of 119 patients with donor chimerism results available for ≥4 years post-HCT, 50% had >95%, 22% had 50% to 95%, 7% had 20% to 50% and 25 (21%) had <20% donor chimerism. Organ dysfunction was identified in 10% pre-HCT and in 20% post-HCT even without complete clinical details on all patients. Hypogonadism and elevated creatinine for age were most commonly reported and significantly higher in recipients ≥ 7 years at the time of HCT (P = .007) and in those with pre-existing morbidity before HCT (P = .02). Outcomes were unaffected by pre-HCT ferritin or GVHD. Mean z scores for height and weight were low at baseline and remained low post-HCT (79%), confirming that growth impairment from disease lacked recovery post-HCT during this follow-up period. HCT for ß-thalassemia has a high rate of cure and low mortality, especially in the young and from HLA-matched related donors. Half of the number of recipients live with mixed chimerism that requires continued follow-up because of a risk of late graft rejection (14%). Organ function after HCT when <7 years of age was generally preserved. Hypogonadism, renal dysfunction, and growth impairment that failed to correct were late complications identified most frequently in older transplant recipients. Systematic follow-up of individual organs such as lung and heart were inadequate but important. These data support the development of simple measures of uniformly tracking long-term HCT outcomes and organ functions in children and adolescents who undergo HCT for thalassemia, allowing for systematic identification and implementation of standardized surveillance strategies and interventions.

Investigation of the Importance of Knee Position during Femoral Tunnel Reaming; Figure 4 versus Hyperflexion.

Introduction: We aimed to compare whether the visualisation provided by arthroscopic hyperflexion and Figure 4 has an effect on femoral tunnel placement in patients undergoing single bundle Anterior Cruciate Ligament Reconstruction (ACLR). Material and methods: We retrospectively evaluated 93 patients who underwent single-band ACLR for Anterior Cruciate Ligament (ACL) injury between 2016 and 2019. Eighty patients met the inclusion criteria with a minimum follow-up of 12 months. We divided the patients into Group 1 (figure 4) and Group 2 (hyperflexion). We analysed the demographic, radiological and functional outcomes of the patients. The functional Lysholm score, operative time, radiological Quadrant method (% proximal-distal and % anterior-posterior) measurements, tunnel lengths, axial and coronal plane angles, and iatrogenic chondral injury in the medial femoral condyle were evaluated. Results: Iatrogenic chondral injury developed in the medial femoral condyle in a total of seven patients in both groups: one patient in group 1 (Figure 4) and six patients in group 2 (Hyperflexion). Although statistically insignificant, iatrogenic medial femoral condyle damage was less in group 1. The statistical analysis between surgical operation time (p = 0.046) and tunnel lengths (p = 0.042) was significant. Conclusion: The position of figure 4 provides visualisation of lateral intercondylar notch better than hyperflexion. In the reaming stage, the medial femoral condyle is less damaged in group 1 (Figure 4). In ACLR, which has a long learning curve, short surgery time is seen as an important advantage for surgeons who have just started doing ACLR. We think that it can be used as an alternative method to hyperflexion in the learning process and maybe shorten the learning curve process.

Hematopoietic stem cell transplantation in children with Griscelli syndrome type 2: a single-center report on 35 patients.

In 2010, we reported the outcome of hematopoietic stem cell transplantation (HSCT) in 11 children with Griscelli syndrome type 2 (GS2). We report here the update on this cohort to include 35 patients. Twenty-seven (77%) patients received conditioning regimen including busulfan, cyclophosphamide with etoposide. Eight (23%) were given busulfan, fludarabine. Thiotepa was added to busulfan and fludarabine regimen in two patients; one received haploidentical marrow and one unrelated cord blood. Posttransplant clinical events included veno-occlusive disease (n = 7), acute (n = 8), or chronic (n = 1) graft-versus-host disease II-IV. With a mortality rate of 37.1% (n = 13) and a median follow-up of 87.7 months of the survivors, 5-year cumulative probability of overall survival (OS) for our cohort of patients was 62.7% (±8.2%). Cumulative probability of 5-year OS was significantly better in those who did not have hemophagocytic lymphohistiocytosis (HLH) prior to HSCT (100% vs. 53.3 ± 9.5%, P value: 0.042). Of the 16 patients with neurologic involvement before HSCT, 8 survived and 3 presented sequelae. OS at 5-year was 50 ± 12.5% and 73.3 ± 10.2% (P value: 0.320) in patients with and without CNS involvement, respectively. In conclusion, HSCT in patients with GS2 is potentially curative with long-term disease-free survival. Early HSCT before the development of the accelerated phase is associated with a better outcome.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic 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. While 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. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, 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 (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

Haematopoietic stem cell transplant for hyper-IgM syndrome due to CD40 defects: a single-centre experience.

Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare disease with only a few reported cases of haematopoietic stem cell transplantation (HSCT). In retrospective study, we reviewed all patients with HIGM3 who underwent HSCT at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between 2008 and 2013. Six patients were identified. Three male and three female patients from three families. The median age of diagnosis was 13 months (range, 1-28 months). All lacked CD40 expression on B cells by flow cytometry. The median time from diagnosis to transplantation was 8.5 months (range, 1-17 months). For all patients, the donors were HLA-identical siblings, with the exception of one patient for whom the donor was a sibling with one antigen mismatch. The conditioning regimen was busulfan and cyclophosphamide in five patients and busulfan, cyclophosphamide and antithymocyte globulin in one patient. For GVHD prophylaxis, cyclosporine and methotrexate was used. All patients engrafted. The survival rate was 100%, with a median follow-up of 54 months (range, 30-116 months). One patient developed acute GVHD. All patients showed complete immune recovery with positive CD40 expression on B cells and discontinued IVIG replacement. Our study shows that HSCT is potentially effective at curing the disease.

Matched-related allogeneic stem cell transplantation in Saudi patients with Fanconi anemia: 10 year's experience.

Allogeneic SCT is curative for bone marrow failure in Fanconi anemia (FA) patients but the optimal conditioning regimen is undetermined. We report here our experience with 56 FA patients who underwent allogeneic matched related SCT. The conditioning regimen varied according to time of SCT and disease status at SCT; 22 patients (group A) received Cy 20 mg/kg, thoraco-abdominal radiation and antithymocyte globulins (ATG); and 34 patients (group B) received Cy 60 mg/kg and ATG. Median time to engraftment was similar (14 days) in both groups. Hemorrhagic cystitis was significantly more common in group B. Overall survival and event-free survival of all patients were 85 and 78.3% respectively. For groups A and B respectively, overall survival was 72.5 and 96.9% (P=0.013); and event-free survival was 72.5 and 82.3% (P=0.3). The use of the nonradiation Cy/ATG regimen in matched related SCT for FA patients offers better overall and event-free survival.

Allogeneic stem cell transplantation in Fanconi anemia patients presenting with myelodysplasia and/or clonal abnormality: update on the Saudi experience.

In the literature, there is an abundance of promising data on the outcome of allogeneic stem cell transplantation (SCT) in patients with Fanconi anemia (FA); however, the data on the outcome of FA patients who present with myelodysplasia and/or abnormal clone are sketchy as the entity itself is a rare one, although, it is believed that the presence of any of these factors confers a worse prognosis on the outcome of the transplant. This is an update of our experience in 11 such patients who underwent SCT at King Faisal Specialist Hospital and Research Center; 10 from the matched and related donors and 1 from a partially matched unrelated cord blood unit; the conditioning was with the same regimen consisting of cyclophosphamide (total of 20 mg/kg), anti-thymocyte globulin (total dose 160 mg/kg of the equine product or 52 mg/kg of the rabbit product) and total-body irradiation at 450 cGy. Ten patients remain currently alive, well and with no evidence of disease, with a median follow-up of almost 4 years.

First report of pediatric hematopoietic stem cell transplantation activities in the eastern mediterranean region from 1984 to 2011: on behalf of the pediatric cancer working committee of the eastern mediterranean blood and marrow transplantation group.

To describe the hematopoietic stem cell transplantation (HSCT) activities for children in the Eastern Mediterranean (EM) region, data on transplants performed for children less than 18 years of age between 1984 and 2011 in eight EM countries (Egypt, Iran, Jordan, Lebanon, Oman, Pakistan, Saudi Arabia and Tunisia) were collected. A total of 5187 transplants were performed, of which 4513 (87%) were allogeneic and 674 (13%) were autologous. Overall, the indications for transplantation were malignant diseases in 1736 (38.5%) and non-malignant in 2777 (61.5%) patients. A myeloablative conditioning regimen was used in 88% of the allografts. Bone marrow (BM) was the most frequent source of stem cells (56.2%), although an increasing use of PBSC was observed in the last decade. The stem cell source of autologous HSCT has shifted over time from BM to PBSC, and 80.9% of autologous HSCTs were from PBSCs. The donors for allogeneic transplants were matched-related in 94.5% of the cases, and unrelated transplants, mainly cord blood (99%) in 239 (5.5%) cases. This is the first report to describe the pediatric HSCT activities in EM countries. Non-malignant disorders are the main indication for allogeneic transplantation. Frequency of alternate donor transplantation is low.

Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy.

In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLA-matched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.

Allogeneic stem cell transplantation for patients with congenital amegakaryocytic thrombocytopenia (CAT).

Five patients with confirmed congenital amegakaryocytic thrombocytopenia (CAT) underwent stem cell transplantation (SCT) from HLA-matched related donors at King Faisal Specialist Hospital and Research Center (KFSHRC). The median age at SCT was 3.2 years (range, 0.4-5 years). Conditioning regimen consisted of busulfan (BU) 4 mg/kg p.o. for 4 days (total dose of 16 mg/kg), and cyclophosphamide (CY) 50 mg/kg once daily i.v. for 4 days (total dose of 200 mg/kg). Antithymocyte globulin (ATG) was given i.v. at a dose of 30 mg/kg for 4 days pre-SCT (total of 120 mg/kg); graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and methotrexate. Four patients engrafted and are alive and transfusion independent with a median follow up time of 30 months (range, 16-45 months). One patient failed to engraft and underwent a second SCT 4 months later but died of respiratory failure. We conclude that the use of allogeneic SCT may be curative for such patients.

Bone marrow transplantation from matched siblings in patients with fanconi anemia utilizing low-dose cyclophosphamide, thoracoabdominal radiation and antithymocyte globulin.

Nineteen patients with Fanconi anemia (FA) and bone marrow failure underwent bone marrow transplantation (BMT) from matched siblings. Median age at BMT was 8.7 years. Conditioning consisted of low-dose cyclophosphamide (CY 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI 400 cGy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) in 13 patients and CsA plus methotrexate in 6 patients. Antithymocyte globulin (ATG) was added in the pretransplant as well as the post-transplant period. All patients received high-dose acyclovir from day 2 pre-BMT to day 28 post BMT, and intravenous immunoglobulins (IVIG), 500 mg/kg weekly from day 7 pre-BMT to day 90 post BMT. No fungal prophylaxis was given. All patients engrafted, (median, 14 days for an absolute neutrophil count > or =0.5 x 10(9)/l; median, 37 days for platelet count > or =20 x 10(9)/l). Fourteen (74%) patients are alive with sustained engraftment and are transfusion independent. Three (16.6%) patients developed acute GVHD; none developed chronic GVHD. Five (26%) patients developed invasive fungal infections, and two (10%) developed fatal CMV disease. We believe the addition of ATG may have contributed to the increased incidence of severe life-threatening fungal and viral infections in our series.

Transfusion-dependent congenital dyserythropoietic anemia type I successfully treated with allogeneic stem cell transplantation.

Until recently, therapy for patients with severe congenital dyserythropoietic anemia (CDA) has been limited to blood transfusions and chelation therapy. Three children with transfusion-dependent CDA type I underwent allogeneic stem cell transplantation (SCT) from matched sibling donors. Conditioning was with cyclophosphamide 50 mg/kg/day for 4 days, busulphan 4 mg/kg/day for 4 days, and antithymocyte globulin (ATG) 30 mg/kg for four doses pre-SCT. All patients engrafted and are alive, and transfusion independent. To our knowledge, this is the first report of successful SCT in the management of CDA type I.

Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation.

Five patients with confirmed Fanconi's anemia (FA) and myelodysplasia and/or leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC. The median age at SCT was 12.6 year (range, 6.2-15 years). Conditioning regimen consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median time to engraftment (defined as ANC>/=0.5 x 10(9)/l) was 16 days (range, 12-26 days). The median time to a self-sustaining platelet count of >/=20 x 10(9)/l was 27 days (range, 12-40 days). All patients engrafted. Two patients developed acute GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one patient developed chronic GVHD of the liver. Four are alive and well with no evidence of the disease; one patient died of bacterial sepsis after controlling her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing SCT is adequate; the regimen is well tolerated and may be curative for such patients.

Hemophagocytic syndrome.

Full text is available as a scanned copy of the original print version.

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure.

BM failure (BMF) is a major and frequent complication of dyskeratosis congenita (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative treatment for BMF associated with this condition. Transplant-related morbidity/mortality is common especially after myeloablative conditioning regimens. Herein, we report nine cases of patients with DKC who received an allo-SCT at five different member centers within the Eastern Mediterranean Blood and Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC patients (male, 7 and female, 2), with a median age at transplantation of 19.1 (4.9-31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal-related donors (100%). Preparative regimens varied according to different centers, but was reduced intensity conditioning (RIC) in eight patients. Graft source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four (44%) cases. The median stem cell dose was 6.79 (2.06-12.4) × 10(6) cells/kg body weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate mofetil were added in five (56%) and two (22%) cases, respectively. Anti-thymocyte globulin was administered at various doses and scheduled in four (44%) cases. Median time-to-neutrophil engraftment was 21 (17-27) days. In one case, late graft failure was noted at 10.4 months post allo-HSCT. Only one patient developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one case, whereas limited chronic GVHD occurred in another four cases. At a median follow-up of 61 (0.8-212) months, seven (78%) patients were still alive and transfusion independent. One patient died of metastatic gastric adenocarcinoma and graft failure was the cause of death in another patient. This study suggests that RIC preparative regimens are successful in inducing hematopoietic cell engraftment in patients with BMF from DKC. Owing to the limited sample size, the use of registry data and heterogeneity of preparative as well as GVHD prophylaxis regimens reported in this series, we are unable to recommend a particular regimen to be considered as the standard for patients with this disease.

Hematopoietic SCT in children with Griscelli syndrome: a single-center experience.

In total, 11 consecutive pediatric patients with Griscelli syndrome (GS) type 2, who received allogeneic hematopoietic SCT (aHSCT) at our center between 1993 and 2007, were reviewed. The median age at transplantation was 8.2 months (range, 4-36.3 months) and the median time from diagnosis to transplantation was 3.7 months (range, 1.4-19.5 months). Seven patients developed an accelerated phase and were treated with chemotherapy before transplantation. At the time of transplantation, all patients were in clinical remission. The source of grafts was matched-related marrows in eight patients and partially mismatched unrelated cords in three patients. All patients were engrafted at a median time of 15 days (range, 12-36 days). Grade I-II acute GVHD and veno-occlusive disease occurred in three and one patient, respectively. A total of 10 patients are now alive and disease free at a median of 4.8 years post-HSCT. The post transplant course was complicated by CMV infection in four patients. One patient died in remission from septic shock, 6 months after transplantation. Chimerism studies at the last contact are available for nine patients: six patients have complete donor chimerism and three have stable mixed chimerism. Early aHSCT from matched-related donors or unrelated cord blood for children with GS is feasible.

Unrelated cord blood transplantation in pediatric patients: a report from Saudi Arabia.

In unrelated cord blood (UCB) transplantation, survival has been shown to correlate with the degree of HLA matching. Thus, to extend transplant access to different ethnic backgrounds, many western UCB transplantation banks now encourage donation from non-Caucasians. Until recently, Saudi Arabia did not have a national UCB bank. In this study we report our experience in UCB transplantation in children using units procured from western cord blood banks. A total of 97 children underwent unrelated UCB transplantation at King Faisal Specialist Hospital and Research Center (KFSHRC), of which 95 were of Arab ethnicity. A total of 30 patients had malignant disorders, 25 patients had non-malignant hematological disorders and 42 patients had inborn errors. Conditioning was according to disease, with six patients receiving reduced-intensity regimens. In all, 46 patients received one-Ag-mismatched units and 51 received two-Ag-mismatched units. Engraftment occurred in 93% of patients, the 100-TRM was 15%, acute GVHD developed in 20% of patients and chronic GVHD occurred in 9% of patients. The 5-year OS and EFS estimates were 52 and 43%, respectively. The search for UCB transplantation units for Saudi patients in western banks yielded reasonably compatible units for our patients; the results are consistent with published data. Our data are encouraging for UCB transplant programs in countries in which there are no national UCB transplantation banks.