Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.

Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study.

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.

Prevention of oral mucositis with cryotherapy in children undergoing hematopoietic stem cell transplantations-a feasibility study and randomized controlled trial.

PURPOSE: To evaluate the feasibility of oral cryotherapy (OC) in children and to investigate if OC reduces the incidence of severe oral mucositis (OM), oral pain, and opioid use in children undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Fifty-three children, 4-17 years old, scheduled for HSCT in Sweden were included and randomized to OC or control using a computer-generated list. OC instructions were to cool the mouth with ice for as long as possible during chemotherapy infusions with an intended time of ≥ 30 min. Feasibility criteria in the OC group were as follows: (1) compliance ≥ 70%; (2) considerable discomfort during OC < 20%; (3) no serious adverse events; and (4) ice administered to all children. Grade of OM and oral pain was recorded daily using the WHO-Oral Toxicity Scale (WHO-OTS), Children's International Oral Mucositis Evaluation Scale, and Numerical Rating Scale. Use of opioids was collected from the medical records. RESULTS: Forty-nine children (mean age 10.5 years) were included in analysis (OC = 26, control = 23). The feasibility criteria were not met. Compliance was poor, especially for the younger children, and only 15 children (58%) used OC as instructed. Severe OM (WHO-OTS ≥ 3) was recorded in 26 children (OC = 15, control = 11). OC did not reduce the incidence of severe OM, oral pain, or opioid use. CONCLUSION: The feasibility criteria were not met, and the RCT could not show that OC reduces the incidence of severe OM, oral pain, or opioid use in pediatric patients treated with a variety of conditioning regimens for HSCT. TRIAL REGISTRATION: ClinicalTrials.gov id: NCT01789658.

Reduced Risk of Sinusoidal Obstruction Syndrome of the Liver after Busulfan-Cyclophosphamide Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplantation.

The aim of this study is to evaluate the incidence of sinusoidal obstruction syndrome (SOS) of the liver and the clinical outcome after hematopoietic stem cell transplantation (HSCT) based on several modifications in our protocols. We retrospectively investigated 372 patients undergoing myeloablative conditioning with oral busulfan (Bu) and cyclophosphamide before allogeneic HSCT during 1990-2015. Patients' supportive care was changed in order to reduce the regimen-related toxicities. Norethisterone use was terminated in 1998, therapeutic drug monitoring of Bu was initiated in 2000, and the use of liver supportive drugs, such as ursodeoxycholic acid and N-acetyl-L-cysteine, were started in 2002 and 2009, respectively. In total, 26 patients (7.0%) developed SOS at a median of 19 days after transplantation. Of these 26 patients, 20 died at a median of 119 days after HSCT and 102 days after the diagnosis of SOS. The incidence of SOS decreased over time in accordance with the improvements in supportive care. The highest incidence of SOS was during 1995-1999 (16.2%) compared with 2.3% during 2010-2015. Overall survival for patients with SOS was 62%, 46%, and 27% at 100 days, 1 year, and 5 years after HSCT, respectively, compared with 92%, 77%, and 66% for those who did not develop SOS (P < 0.001). In conclusion, the incidence of SOS and related deaths were significantly decreased over the last years. Our institution pursues massive preventative and personalized measures for SOS. This strategy may also be applicable in other conditioning protocols in order to reduce the incidence of SOS and, hence, improve the clinical outcome.

Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia.

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease.

There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so-called decidua stromal cells (DSCs), are more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients (median age, 49 years; range, 1.6 to 72 years) for grade II-IV acute GVHD. All 21 patients had biopsy-proven gastrointestinal GVHD. The majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days, and 10 were refractory to steroids after >3 days. We used an improved protocol in which DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (range, 0.9 to 2.9) × 106 cells/kg body weight with a median of 2 (range, 1 to 6) doses, given 1 week apart. The median viability of thawed DSCs was 93% (range, 69% to 100%), and the median cell passage number was 4 (range, 2 to 4). Complete resolution of GVHD was seen in 11 patients, with a partial response in the other 10. The cumulative incidence of chronic GVHD was 52%. GVHD was mild in 6 patients, moderate in 4 patients, and severe in 1 patient based on National Institutes of Health chronic GVHD severity scoring. Nine patients died, including 3 from relapse and 1 each from acute GVHD and septicemia, Zygomycetes infection, liver insufficiency, cerebral hemorrhage, multiple organ failure, and chronic GVHD with obstructive bronchiolitis. Four-year transplantation-related mortality was 28.6%, and overall survival was 57%. Survival was similar (P = .33) to that for all 293 patients who underwent allogeneic hematopoietic cell transplantation during the same period (2012 to 2015), with 66% overall survival. DSC infusion is a novel therapy for acute GVHD grade II-IV, and a randomized trial is currently underway (ClinicalTrials.gov NCT02172937).

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study.

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted.

Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience.

The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10-3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10-3 . After a median follow-up of 5·5 years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5-47·7) for MRD-positive versus 5·1% (95% CI: 1·3-19·2), P = 0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6-51·0, P = 0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4-97·2) and 67·4% (95% CI: 50·2-90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.

The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Inherited Diseases Is Influenced by HLA Match, Year of Transplantation, and Immunized Female Donor.

BACKGROUND: For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure. METHODS: We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38). RESULTS: Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05). CONCLUSIONS: The outcome after HSCT for IEM depends on HLA match, year and immune female donor.

Long-term health outcomes in survivors of childhood AML treated with allogeneic HSCT: a NOPHO-AML Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves event-free survival in acute myeloid leukemia (AML); however, the burden of late effects may be increased. We compared health-related outcomes in childhood AML survivors treated according to the NOPHO-AML protocols either with or without allo-HSCT at age < 21 years. Out of the 147 eligible AML survivors treated with allo-HSCT, 95 (65%) and 53 (75%) of their eligible siblings completed a questionnaire. Their data were compared to corresponding data collected previously from NOPHO-AML survivors treated with chemotherapy only (CT) (n = 101). The median follow-up was 12 (range 2-28) years after allo-HSCT and 47% had received total body irradiation (TBI)-based conditioning. Allo-HSCT survivors reported significantly more physical health limitations (39% vs 7%, p < 0.005), medications for cardiovascular disease (10% vs 1%, p < 0.05) and use of analgesics (32% vs 11%, p < 0.01) than CT survivors. Health problems prevented 16% of the allo-HSCT survivors from attending school or managing a job vs. 3% among CT survivors (p < 0.05). Among 73 allo-HSCT survivors (age ≥ 15 years), seven females reported natural pregnancies and three males reported unassisted conceptions in partners. Survivors of childhood AML treated with allo-HSCT experienced more physical health limitations and used more medications than the survivors treated with chemotherapy only.

[Cistus - queen of teas]. / Czystek ­ królowa herbat.

The aim of our article is to present a healthy qualities of Cistus. Cistus is plant belonging to the Cistaceae has strong health-promoting properties through its antioxidant, immunomodulatory, bacteriostatic and antifungal activities. Cistus has an inhibitory effect on the multiplication of viruses, which can be used to treat cold and influenza. A significant effect of the Cistus on stopping the growth and proliferation of prostatic cells was also demonstrated, which evidence of cytotoxic and antiproliferative activity. This activity can be used in both benign and malignant prostatic enlargement, as well as adjuvant in the treatment of other cancers. Extract from Cistus through modulation of immune system significantly strengthens immunity and has antiallergic activity. Cistus has a lot of polyphenols that destroy free radicals, inhibit the formation and development of inflammation in the body, strengthen, energize, and have a preventive effect on cardiovascular diseases. Through bioflavonoids, it works synergistically with vitamin C, enhancing its action, and also protects the mucous membrane of the stomach, preventing the formation of ulcers, or helping to treat them. Because of healing properties, as well as taste qualities the Cistus- teacan be boldly recommended as a daily drink for both young and old people. The promoting the use of infusion from a Cistus along with honey or lemon juice should be as wide as possible.

Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants.

AIM: This prospective study assessed the long-term ocular and visual outcomes of children with mucopolysaccharidoses type I Hurler syndrome (MPS IH) who were treated with haematopoietic stem cell transplants (HSCT). METHODS: Clinical ophthalmological assessments were performed on eight patients at the St Erik Eye Hospital, Huddinge, Stockholm, Sweden, from 2001-2018: The median age at diagnosis and HSCT were 12.2 (range 5.0-16.4) and 16.7 (8.0-20.4) months. The last eye examination was at a median of 13.4 (6.3-19.0) years and follow-up lasted a median of 12.0 (5.0-17.4) years. RESULTS: Poor visual acuity, poor night vision and, or, photophobia were reported by six children. The best corrected visual acuity at the last visit was a median of 0.4 and 0.5 in the right and left eye and had declined significantly in two patients. Corneal opacities had increased despite HSCT in five patients. High hyperopia, at a median of +6 Dioptres, occurred in all patients and stiff corneas in all four patients that were measured. The patients' corrected intraocular pressures were normal. Retinal degeneration was identified in two patients. CONCLUSION: Despite HSCT, the long-term follow-up of patients with MPS IH showed reduced visual acuity due to corneal opacities or retinal degeneration.

Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia - A Swedish nationwide cohort study.

OBJECTIVES: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians. METHODS: We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000-2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade-especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P < .001); and non-severe 88.5% (P < .001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109 /L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival. CONCLUSIONS: Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease.

Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One-year survival in the two groups was 47% (95% confidence interval [CI] 23-68) and 76% (95% CI 51-89), respectively (p = .016). For the SR patients, 1-year survival was 73% (95% CI 37-90) in SR group 2 (n = 11), which was better than 31% (95% CI 11-54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5-42) in BM-MSC treated (n = 15; p = .0015), and 3% (95% CI 0-14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT-02172937.) Stem Cells Translational Medicine 2018;7:325-332.

Visual perceptual skills and visual motor integration in children and adolescents after allogeneic hematopoietic stem cell transplantation.

The aim of the study was to study visual acuity, visual perceptual, and VMI skills in patients after HSCT in childhood. Tests of visual perceptual skills, VMI, and visual acuity were performed in 102 children/adolescents (age range 4.3-20.9 years). Mean time from HSCT to testing was 6.0 years (0.9-17.5 years). Visual acuity was median 1.0 decimal (range 0.16-1.6). Visual perceptual skills (memory, form constancy, visual sequential memory) and VMI were low compared to age-equivalent normative data with, respectively, 36%, 45%, 60%, and 46% of all patients performing below the 25 percentile. All patients performed significantly lower than the 50 percentile in the reference material in visual sequential memory, P < .001 (boys P < .001 and girls P < .05). All patients also performed significantly lower than the 50 percentile in VMI (P < .01) (boys P < .05). Pretransplant conditioning regimen did not affect outcome if the results were corrected for age at HSCT. Visual perceptual skill problems and VMI problems frequently occur in patients after HSCT in childhood. Age at HSCT and original diagnosis influence the outcome. Neuropsychological assessment including visual perception is recommended in children after HSCT.

Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011.

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

NEIL1 is a candidate gene associated with common variable immunodeficiency in a patient with a chromosome 15q24 deletion.

We report the first patient with an interstitial deletion of chromosome 15q24.1-q24.3 associated with common variable immunodeficiency (CVID). The 18-year old female patient's clinical and immunological phenotype was compared with 8 additional previously published patients with chr15q24 deletions. A CGH analysis estimated the deletion to be 3.767Mb in size (chr15: 74,410,916-78,178,418) and the result was confirmed using qRT-PCR. We defined an immune-related commonly deleted region (ICDR) within the chromosomal band 15q24.2, deleted in all four patients with different forms of antibody deficiencies. Mutations in the 14 genes within this ICDR were not identified in the remaining allele in our patient by WES and gene expression analyses showed haploinsufficiency of all the genes. Among these genes, we consider Nei Like DNA Glycosylase 1 (NEIL1) as a likely candidate gene due to its crucial role in B-cell activation and terminal differentiation.

Visual evoked potentials after hematopoietic allogeneic stem cell transplantation in childhood.

OBJECTIVE: To study visual pathway pathology detected by visual evoked potentials (VEPs) in patients treated with hematopoietic stem cell transplantation (HSCT) in childhood and to determine the impact of adverse ocular findings, somatic diseases, and conditioning regimens on the VEP results. METHODS: Ophthalmological assessments including pattern VEPs were performed in 47 of 79 patients at a median age of 15 years (range 3-21 years) in median 6 years (1-17 years) after HSCT. Somatic data were extracted from medical records. RESULTS: Eight patients of 47 (17%) demonstrated pathological VEPs with prolonged latencies bilaterally (n = 3) or unilaterally (n = 5) at their latest VEP test at an age of 12-18 years. A subnormal visual acuity was present in 8/11 eyes with pathological VEPs: one eye had cataract, six eyes had cataract surgery where of two had developed secondary cataracts. One eye had residual retinopathy of prematurity. Pathological VEPs were associated with decreased visual acuity (p = 0.00019) but not linked to gender, malignant diagnosis or conditioning. CONCLUSION: VEP recordings showed an association with decreased visual acuity but no relationship with irradiation or chemotherapy in the present study. SIGNIFICANCE: VEP recordings might be of clinical value for children with an unexplained subnormal visual acuity undergoing HSCT.