Publications by authors named "Jacek Winiarski"

82 Publications

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

Blood Adv 2020 08;4(15):3754-3766

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1182/bloodadvances.2020002101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422132PMC
August 2020

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

Support Care Cancer 2020 Oct 28;28(10):4869-4879. Epub 2020 Jan 28.

Department of Women's and Children's Health, Pediatric Oncology, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1007/s00520-019-05258-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447624PMC
October 2020

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

Clin Transl Sci 2020 03 6;13(2):293-300. Epub 2019 Nov 6.

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/cts.12709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070785PMC
March 2020

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

Blood Adv 2019 10;3(20):3123-3131

British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

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.
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http://dx.doi.org/10.1182/bloodadvances.2019000722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849938PMC
October 2019

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.

Biol Blood Marrow Transplant 2019 10 4;25(10):1970-1974. Epub 2019 Jun 4.

Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.

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.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.032DOI Listing
October 2019

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

Biol Blood Marrow Transplant 2019 10 4;25(10):1965-1969. Epub 2019 Jun 4.

Translational Cell Therapy Research, Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institute, Huddinge, Sweden.

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) × 10 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).
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http://dx.doi.org/10.1016/j.bbmt.2019.05.034DOI Listing
October 2019

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

Br J Haematol 2019 03 24;184(6):982-993. Epub 2019 Jan 24.

Department of Paediatrics, University of Helsinki, Helsinki, Finland.

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 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 . 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.
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http://dx.doi.org/10.1111/bjh.15761DOI Listing
March 2019

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

Transplantation 2019 06;103(6):1247-1252

Translational Cell Therapy Research, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1097/TP.0000000000002481DOI Listing
June 2019

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

Bone Marrow Transplant 2019 05 21;54(5):726-736. Epub 2018 Sep 21.

Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.

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.
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http://dx.doi.org/10.1038/s41409-018-0337-8DOI Listing
May 2019

[Cistus - queen of teas].

Pol Merkur Lekarski 2018 08;45(266):53-56

Students of Medical Faculty.

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.
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August 2018

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

Acta Paediatr 2018 11 23;107(11):1995-2003. Epub 2018 May 23.

Astrid Lindgren Childrens' Hospital, Karolinska University Hospital, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/apa.14368DOI Listing
November 2018

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

Stem Cells Transl Med 2018 04 13;7(4):325-331. Epub 2018 Mar 13.

Translational Cell Therapy Research (TCR), Department of Laboratory Medicine.

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.
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http://dx.doi.org/10.1002/sctm.17-0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866941PMC
April 2018

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

Eur J Haematol 2018 Jun 10;100(6):613-620. Epub 2018 Apr 10.

Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.

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 × 10 /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.
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http://dx.doi.org/10.1111/ejh.13057DOI Listing
June 2018

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

Pediatr Transplant 2018 03 8;22(2). Epub 2018 Feb 8.

Department of Special Education, Stockholm University, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/petr.13117DOI Listing
March 2018

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

Haematologica 2017 10 27;102(10):1683-1690. Epub 2017 Jul 27.

South Älvsborg Hospital Borås, Sweden.

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.
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http://dx.doi.org/10.3324/haematol.2017.169862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622852PMC
October 2017

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

Clin Neurophysiol Pract 2017 2;2:67-71. Epub 2017 Mar 2.

Department of Clinical Neuroscience, Karolinska Institutet and St Erik Eye Hospital, Polhemsgatan 50, SE 112 82 Stockholm, Sweden.

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.
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http://dx.doi.org/10.1016/j.cnp.2017.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123843PMC
March 2017

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

Clin Immunol 2017 Mar 14;176:71-76. Epub 2017 Jan 14.

Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden. Electronic address:

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.
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http://dx.doi.org/10.1016/j.clim.2017.01.006DOI Listing
March 2017

Costs associated with treatment of severe combined immunodeficiency-rationale for newborn screening in Sweden.

J Allergy Clin Immunol 2017 05 21;139(5):1713-1716.e6. Epub 2016 Dec 21.

Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden; Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.

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http://dx.doi.org/10.1016/j.jaci.2016.10.043DOI Listing
May 2017

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year Pilot TREC and KREC Screening Study.

J Clin Immunol 2017 01 21;37(1):51-60. Epub 2016 Nov 21.

Department of Clinical Immunology, Karolinska University Hospital Huddinge, SE-14186, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1007/s10875-016-0347-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226987PMC
January 2017

A prospective randomized trial comparing cyclosporine/methotrexate and tacrolimus/sirolimus as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation.

Haematologica 2016 11 4;101(11):1417-1425. Epub 2016 Aug 4.

Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.

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.
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http://dx.doi.org/10.3324/haematol.2016.149294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394879PMC
November 2016

[Nickel - role in human organism and toxic effects].

Pol Merkur Lekarski 2016 Aug;41(242):115-8

Medical University of Wrocław, Poland: Students of Medical Faculty.

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.
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August 2016

Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades.

Pediatr Transplant 2016 Aug 1;20(5):667-74. Epub 2016 Jun 1.

Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/petr.12723DOI Listing
August 2016

Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation.

J Clin Immunol 2016 07 4;36(5):480-9. Epub 2016 May 4.

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1007/s10875-016-0289-yDOI Listing
July 2016

Both high and low levels of cellular Epstein-Barr virus DNA in blood identify failure after hematologic stem cell transplantation in conjunction with acute GVHD and type of conditioning.

Oncotarget 2016 May;7(21):30230-40

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.

The level of Epstein-Barr virus DNA in blood has proven to be a biomarker with some predictive value in allogeneic hematopoietic stem cell transplantation patients (HSCT). We evaluated the impact of EBV load on survival of 51 patients (32M/19F, median age: 32 years, from < 1 to 68 years old), who had received HSCT for different types of malignancies (49 cases) or non-malignancies (2 cases). The overall survival [1]was compared between patients with extreme and moderate cell bound EBV DNA levels. Different sources of stem-cells (peripheral blood stem, n = 39; bone marrow, n = 9; or umbilical cord blood, n = 3) were used. Twenty patients received reduced-intensity conditioning regimen while the other 31 received myeloablative conditioning. Patients with high or very low level of cell bound EBV-DNA levels had a shorter OS than those with moderate EBV load: OS at 5 years was 67% vs 90% (p < 0.03). There was a conspicuous relationship between EBV load and the reconstitution dynamics of total and EBV-specific T cells, CD4+ and CD4- CD8- (double negative) T cells in the few patients where it was analyzed. This was not statistically significant. Two other factors were associated to early mortality in addition to high or low EBV load: acute GVHD II-IV (p < 0.02) and pre-transplant conditioning with total body irradiation (TBI) ≥6 Gy, (p < 0.03). All the patients meeting all three criteria died within two years after transplantation. This points to a subgroup of HSCT patients which deserve special attention with improvement of future, personalized treatment.
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http://dx.doi.org/10.18632/oncotarget.8803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058676PMC
May 2016

HLA, GVHD, and parenteral nutrition are risk factors for hepatic complications in pediatric HSCT.

Pediatr Transplant 2016 Feb 31;20(1):96-104. Epub 2015 Oct 31.

Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/petr.12623DOI Listing
February 2016

Cataract after allogeneic hematopoietic stem cell transplantation in childhood.

Acta Paediatr 2016 Jan;105(1):82-9

Department of Paediatrics, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/apa.13173DOI Listing
January 2016

Chimerism analysis in clinical practice and its relevance for the detection of graft rejection and malignant relapse in pediatric hematopoietic stem cell transplant patients.

Pediatr Transplant 2015 Nov 20;19(7):758-66. Epub 2015 Aug 20.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

Chimerism and clinical outcome data from 244 hematopoietic stem cell transplants in 218 children were retrospectively analyzed to assess their relevance for the detection of graft rejection and malignant relapse. Patients transplanted for a non-malignant disease had significantly higher proportions of residual recipient T cells in peripheral blood at one, three, and six months compared with patients transplanted for malignant disease. Recipient T-cell levels were below 50% at one month after transplantation in most patients (129 of 152 transplants). Graft rejection occurred more frequently in the group of patients with high levels of recipient cells at one month (10 graft rejections in the 23 patients with recipient T cells >50% at one month as compared to seven graft rejections occurred in 129 patients with recipient T cells <50% (p < 0.001). Multilineage chimerism data in 87 children with leukemia at one, three, and six months after transplantation were not correlated with subsequent relapse of malignant disease. In conclusion, early analysis of lineage-specific chimerism in peripheral blood can be used to identify patients who are at high risk of graft rejection. However, the efficacy of early chimerism analysis for predicting leukemia relapse was limited.
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http://dx.doi.org/10.1111/petr.12580DOI Listing
November 2015

Hypogammaglobulinemia in children after allogeneic hematopoietic stem cell transplantation: a cytokine mediated immunoglobulin isotype class switch arrest?

Pediatr Blood Cancer 2015 May 26;62(5):890-6. Epub 2015 Jan 26.

Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC); and; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Background: Hypogammaglobulinemia (hypo-IgG) is common early post-HSCT in children, occasionally necessitating long-term immunoglobulin (Ig) G replacement therapy. IgG replacement may not reduce mortality, although infectious complications are decreased

Procedure: Clinical data and samples from 86 children were analyzed retrospectively with the aim to identify risk factors for developing long-term hypo-IgG (i.e., requiring ≥ 3 months IgG replacement) post-HSCT and studying the underlying biology. Laboratory studies covered serum cytokines, IGHG2 genotyping and routine laboratory investigations. Results were analyzed statistically.

Results: Forty-eight percent of the children developed long-term hypo-IgG. These children were younger (<5 years) and had higher acute GvHD incidence, but had better overall survival (88% vs. 69%, P = 0.036). Significantly lower Ig levels post-HSCT but equal immune cell recovery were seen in patients with long-term hypo-IgG compared with those of transient or no hypo-IgG. Pre-HSCT IL-6 and -7 and post-HSCT BAFF and APRIL levels were significantly higher in the long-term hypo-IgG group.

Conclusions: Findings suggests an unfavorable cytokine milieu for graft-derived immune recovery, possibly inducing Ig isotype class switch arrest. Younger age, acute GvHD, and higher pre-HSCT IL-6 levels were identified as significant risk factors for long-term hypo-IgG. Long-term hypo-IgG post-HSCT does not need to be unfavorable and could be an effect of deteriorated cytokine signaling.
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http://dx.doi.org/10.1002/pbc.25409DOI Listing
May 2015

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

Br J Haematol 2015 Apr 18;169(1):103-10. Epub 2014 Dec 18.

Hospital Saint Louis, AP-HP, and IUH University Paris VII, Eurocord, Paris, France; Centro de Oncologia, Hospital Sirio-Libanes, Sao Paulo, Brazil.

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.
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http://dx.doi.org/10.1111/bjh.13267DOI Listing
April 2015
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