ABSTRACT
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.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Wiskott-Aldrich Syndrome , Busulfan/therapeutic use , Child, Preschool , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Retrospective Studies , Tissue Donors , Transplantation Conditioning/methods , Treatment Outcome , Wiskott-Aldrich Syndrome/therapyABSTRACT
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.
Subject(s)
Cryotherapy/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Stomatitis/prevention & control , Adolescent , Child , Child, Preschool , Feasibility Studies , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Incidence , Male , Pain/etiology , Pain/prevention & control , Stomatitis/etiology , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methodsABSTRACT
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)â¯×â¯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 (Pâ¯=â¯.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).
Subject(s)
Decidua/metabolism , Graft vs Host Disease/genetics , Placenta/metabolism , Stromal Cells/metabolism , Acute Disease , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Graft vs Host Disease/mortality , Humans , Infant , Male , Middle Aged , Pilot Projects , Pregnancy , Prospective Studies , Survival Analysis , Young AdultABSTRACT
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%; Pâ¯=â¯.023), which translated into a lower 5-year OS: 70.6% versus 92.2% (Pâ¯=â¯.022) and a trend of lower GRFS (52.9% versus 74.5%; Pâ¯=â¯.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.
Subject(s)
Anemia, Aplastic/therapy , Adolescent , Adult , Aged , Anemia, Aplastic/pathology , Child , Child, Preschool , Cohort Studies , Female , Graft vs Host Disease/mortality , Humans , Male , Middle Aged , Recurrence , Sweden , Tissue Donors , Unrelated Donors , Young AdultABSTRACT
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.
Subject(s)
Neoplasm, Residual/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Acute Disease , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Neoplasm, Residual/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Risk FactorsABSTRACT
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.
Subject(s)
Anemia, Aplastic/drug therapy , Antilymphocyte Serum/therapeutic use , Immunosuppressive Agents/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Anemia, Aplastic/diagnosis , Anemia, Aplastic/epidemiology , Anemia, Aplastic/immunology , Biomarkers , Child , Child, Preschool , Cohort Studies , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation , Humans , Incidence , Male , Middle Aged , Odds Ratio , Severity of Illness Index , Survival Analysis , Sweden/epidemiology , Young AdultABSTRACT
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.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Perceptual Disorders/etiology , Psychomotor Disorders/etiology , Psychomotor Performance , Vision Disorders/etiology , Visual Acuity , Visual Perception , Adolescent , Child , Child, Preschool , Female , Hematopoietic Stem Cell Transplantation/psychology , Humans , Longitudinal Studies , Male , Neuropsychological Tests , Perceptual Disorders/diagnosis , Psychomotor Disorders/diagnosis , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Vision Disorders/diagnosisABSTRACT
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.
Subject(s)
Cornea/physiopathology , Hematopoietic Stem Cell Transplantation , Mucopolysaccharidoses/complications , Retina/physiopathology , Vision Disorders/etiology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Mucopolysaccharidoses/physiopathology , Mucopolysaccharidoses/therapy , Prospective Studies , Refraction, Ocular , Strabismus , Visual Acuity , Young AdultABSTRACT
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.
Subject(s)
Cistus/chemistry , Polyphenols/pharmacology , Teas, Herbal/analysis , Animals , Anti-Infective Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Cistus/adverse effects , Humans , Teas, Herbal/adverse effectsABSTRACT
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.
Subject(s)
Chromosome Disorders/genetics , Common Variable Immunodeficiency/genetics , DNA Glycosylases/genetics , Intellectual Disability/genetics , Adolescent , B-Lymphocytes/immunology , Cell Differentiation/immunology , Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Female , Humans , Lymphocyte Activation/geneticsABSTRACT
Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with beta-actin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated. Sixty-four children were recalled for follow-up due to low TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID, ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were identified. Of the positive samples, 24 were associated with prematurity. Thirteen children born to mothers treated with immunosuppressive agents during pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously normalized. Twenty-nine newborns had no apparent cause identified for their abnormal results, but normalized with time. Children with trisomy 21 (n = 43) showed a lower median number of both TREC (104 vs. 174 copies/µL blood) and KREC (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below the cutoff level. Two children diagnosed with DiGeorge syndrome were found to have low TREC levels, but these were still above the cutoff level. This is the first large-scale screening study with a simultaneous detection of both TREC and KREC, allowing identification of newborns with both T and B cell defects.
Subject(s)
Neonatal Screening , Severe Combined Immunodeficiency/diagnosis , Female , Genetic Testing/methods , Gestational Age , Humans , Infant, Newborn , Male , Multiplex Polymerase Chain Reaction , Neonatal Screening/methods , Phenotype , Real-Time Polymerase Chain Reaction , Receptors, Antigen, T-Cell/genetics , Recombination, Genetic , Risk Factors , Sequence Deletion , Severe Combined Immunodeficiency/genetics , SwedenABSTRACT
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.
Subject(s)
Anemia, Aplastic/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Anemia, Aplastic/diagnosis , Anemia, Aplastic/history , Anemia, Aplastic/therapy , Child , Child, Preschool , Combined Modality Therapy , Female , History, 21st Century , Humans , Incidence , Male , Middle Aged , Patient Outcome Assessment , Population Surveillance , Proportional Hazards Models , Registries , Retrospective Studies , Severity of Illness Index , Survival Analysis , Sweden/epidemiology , Young AdultABSTRACT
PURPOSE: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. METHODS: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. RESULTS: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed. CONCLUSIONS: Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Anemia, Hemolytic, Autoimmune/therapy , B-Lymphocytes/immunology , Common Variable Immunodeficiency/therapy , Hematopoietic Stem Cell Transplantation , Killer Cells, Natural/immunology , Sequence Deletion/genetics , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/genetics , Autoimmunity , Child , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/genetics , Consanguinity , DNA Mutational Analysis , HLA Antigens/immunology , Histocompatibility , Humans , Immunoglobulins/blood , Male , Treatment OutcomeABSTRACT
Improvement of graft-versus-host disease prophylaxis remains an important goal in allogeneic hematopoietic stem cell transplantation. Based on reports of possibly preferential properties of sirolimus, we compared the standard regimen of cyclosporine and methotrexate (n=106) with a combination of tacrolimus and sirolimus (n=103) as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation in a prospective, open, randomized trial. The hypothesis was that the tacrolimus/sirolimus regimen would lead to less acute graft-versus-host disease and reduced transplant-related mortality. There was no significant difference in the cumulative incidence of acute graft-versus-host disease of grades II-IV (41% vs. 51%; P=0.19) or grades III-IV (13% vs. 7%; P=0.09) between the groups. Time to neutrophil engraftment (18 days vs. 17 days; P=0.24) was similar, but time to platelet engraftment was longer in cyclosporine/methotrexate patients (14 vs. 12 days; P<0.01). No significant differences in incidence of oropharyngeal mucositis, time to full donor chimerism, or number of cytomegalovirus infections were seen between the two treatment arms, and transplant-related toxicities were equally distributed. Triglyceride (P=0.005) and cholesterol (P=0.009) levels were higher in tacrolimus/sirolimus patients. Transplant-related mortality (18% vs. 12%; P=0.40) and 5-year overall survival (72% vs. 71%; P=0.71) were similar. Five-year relapse-free survival in patients with malignant diagnoses was 65% in the cyclosporine/methotrexate group and 63% in the tacrolimus/sirolimus group (P=0.73). We conclude that tacrolimus/sirolimus remains a valid and safe alternative to cyclosporine/methotrexate as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation, with comparable transplant-related outcomes. The trial was registered at clinicaltrials.gov identifier: 00993343.
Subject(s)
Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Premedication/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Cyclosporine/therapeutic use , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Infant , Methotrexate/therapeutic use , Middle Aged , Neutrophils/cytology , Platelet Count , Premedication/mortality , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Transplantation, Homologous , Treatment Outcome , Young AdultSubject(s)
Cancer Survivors/statistics & numerical data , Hematopoietic Stem Cell Transplantation , Hospitalization/statistics & numerical data , Leukemia, Myeloid, Acute/therapy , Adult , Aged , Allografts , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cardiovascular Diseases/epidemiology , Combined Modality Therapy , Digestive System Diseases/epidemiology , Endocrine System Diseases/epidemiology , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infections/epidemiology , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/epidemiology , Male , Middle Aged , Musculoskeletal Diseases/epidemiology , Nervous System Diseases/epidemiology , Registries , Remission Induction , Respiration Disorders/epidemiology , Scandinavian and Nordic Countries/epidemiology , Transplantation Conditioning/adverse effects , Young AdultABSTRACT
UNLABELLED: Hepatic dysfunction is common after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to determine the risk factors, frequency, and outcome of hepatic complications post-HSCT in children. Two hundred and thirty-seven cases of allogeneic HSCT in children were included. Data on biochemical liver function at start of HSCT, at +1, +3, +6, and +9 months, and at each subsequent yearly follow-up were extracted. Patients were stratified into groups with hepatocellular (none and mild, and moderate to severe) and hepatobiliary (none and present) dysfunction. Statistical analysis included variables such as diagnosis, age, conditioning regimen, and HLA type. RESULTS: One hundred and fifty-six (66%) patients displayed hepatocellular dysfunction post-HSCT. In most cases transient, but 32% had a persistent abnormality three yr post-HSCT. Risk factors were chronic GVHD (OR 4.20, p = 0.003) and donor HLA-A*01 (OR 2.97, p = 0.02). HLA-DQB1*03 decreased the risk (OR 0.35, p = 0.02). Hepatobiliary dysfunction was less frequent (12%) but carried a poor prognosis. aGVHD grade II-IV (OR 2.7, p = 0.02) and long-term TPN (OR 3.25, p = 0.01) increased the risk. CONCLUSION: GVHD is an important risk factor for liver dysfunction post-HSCT. Specific HLA types may also contribute as a risk factor, while others seem to have a protective effect.
Subject(s)
Graft vs Host Disease/diagnosis , HLA Antigens/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Liver Failure/complications , Parenteral Nutrition, Total/adverse effects , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Graft vs Host Disease/complications , HLA-A Antigens/genetics , HLA-DQ beta-Chains/genetics , Humans , Infant , Liver Failure/diagnosis , Liver Failure/surgery , Male , Prognosis , Retrospective Studies , Risk Factors , Time Factors , Transplantation Conditioning , Transplantation, Homologous/adverse effects , Treatment OutcomeABSTRACT
Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Child , Graft vs Host Disease/prevention & control , Humans , Recurrence , Retrospective Studies , Transplantation, HomologousABSTRACT
AIM: The aim of this study was to study long-term visual outcome and cataract development in children and adolescents after hematopoietic stem cell transplantation (HSCT) in childhood. METHODS: Best corrected visual acuity (BCVA), refraction and lens status were examined in a prospective study of 139 children and adolescents. RESULTS: In total, 139 patients (58 female), median age 6.6 years at HSCT (range 0.4-17.5 years), were followed up for a median of 8.0 years (1-19.4 years). Median BCVA in the better eye was 1.0 decimal. Altogether 19 of 131 patients developed cataract requiring surgery, while 46 developed less prominent lens opacities and 66 had clear lenses at time of latest follow-up. Patients conditioned with total body irradiation had a higher risk of developing lens opacities or cataract (p < 0.0001) as did patients with malignant disease, irrespective of irradiation treatment (p < 0.0001). Cumulative analysis showed that 50% of all patients had developed lens opacities/cataract after 10.2 years. Patients who ultimately needed cataract surgery developed cataract earlier than others (p = 0.006). CONCLUSION: Lens opacities or cataract were more common in children or adolescents with malignant disease and after conditioning with irradiation. Regular ophthalmological follow-up is important after HSCT for early intervention to avoid amblyopia.
Subject(s)
Cataract/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Cataract/diagnosis , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Kaplan-Meier Estimate , Male , Proportional Hazards Models , Prospective Studies , Young AdultABSTRACT
The aim of this study is to familiarize the Role of nickel in the Environment and in living organisms. This metal is widely used in many fields such as electrical engineering, medicine, Jewellery or Automotive Industry. Furthermore, it's an important part of our food. As the central atom of bacterial enzymes it participates in degradation of urea.. Nickel is also an micronutritient essential for proper functioning of the human body, as it increases hormonal activity and is involved in lipid metabolism. This metal makes it's way to the human body through respiratory tract, digestive system and skin. Large doses of nickel or prolonged contact with it could cause a variety of side effects. Harmfull effects of Nickel are genotoxicity haematotoxicity, teratogenicity, immunotoxicity and carcinogenicity. The population of people allergic to nickel is growing, it occcurs much more often to the women and it can appear in many way. Hypersensitivity to nickel can also be occupational. Due to the increasing prevalence of allergies to nickel. European regulations have been introduced to reduce the content of this metal in products of everyday usage. In countries which have fulfilled the above-mentioned law, the plunge of hypersensitivities has been observed.
Subject(s)
Micronutrients/physiology , Nickel/physiology , Environmental Pollutants/adverse effects , Environmental Pollutants/metabolism , Environmental Pollutants/toxicity , Humans , Micronutrients/metabolism , Nickel/adverse effects , Nickel/metabolism , Nickel/toxicityABSTRACT
Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.