Publications by authors named "Bernd Gruhn"

111 Publications

Correction to: Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection.

Eur J Clin Microbiol Infect Dis 2021 Dec 1. Epub 2021 Dec 1.

Institute of Infection Medicine, Christian-Albrechts-Universität zu Kiel and University Medical Center Schleswig-Holstein, Brunswiker Straße 4, 24105, Kiel, Germany.

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http://dx.doi.org/10.1007/s10096-021-04367-3DOI Listing
December 2021

Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences.

Eur Radiol 2021 Oct 20. Epub 2021 Oct 20.

Department of Paediatric Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.

Objectives: To compare the diagnostic value of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the lung versus the gold standard computed tomography (CT) and two T1-weighted MRI sequences in children.

Methods: Twenty-three patients with proven oncologic disease (14 male, 9 female; mean age 9.0 + / - 5.4 years) received 35 low-dose CT and MRI examinations of the lung. The MRI protocol (1.5-T) included the following post-contrast sequences: two-dimensional (2D) incoherent gradient echo (GRE; acquisition with breath-hold), 3D volume interpolated GRE (breath-hold), and 3D high-resolution radial UTE sequences (performed during free-breathing). Images were evaluated by considering image quality as well as distinct diagnosis of pulmonary nodules and parenchymal areal opacities with consideration of sizes and characterisations.

Results: The UTE technique showed significantly higher overall image quality, better sharpness, and fewer artefacts than both other sequences. On CT, 110 pulmonary nodules with a mean diameter of 4.9 + / - 2.9 mm were detected. UTE imaging resulted in a significantly higher detection rate compared to both other sequences (p < 0.01): 76.4% (84 of 110 nodules) for UTE versus 60.9% (67 of 110) for incoherent GRE and 62.7% (69 of 110) for volume interpolated GRE sequences. The detection of parenchymal areal opacities by the UTE technique was also significantly higher with a rate of 93.3% (42 of 45 opacities) versus 77.8% (35 of 45) for 2D GRE and 80.0% (36 of 45) for 3D GRE sequences (p < 0.05).

Conclusion: The UTE technique for lung MRI is favourable in children with generally high diagnostic performance compared to standard T1-weighted sequences as well as CT. Key Points • Due to the possible acquisition during free-breathing of the patients, the UTE MRI sequence for the lung is favourable in children. • The UTE technique reaches higher overall image quality, better sharpness, and lower artefacts, but not higher contrast compared to standard post-contrast T1-weighted sequences. • In comparison to the gold standard chest CT, the detection rate of small pulmonary nodules small nodules ≤ 4 mm and subtle parenchymal areal opacities is higher with the UTE imaging than standard T1-weighted sequences.
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http://dx.doi.org/10.1007/s00330-021-08236-7DOI Listing
October 2021

Analysis of risk factors for hepatic sinusoidal obstruction syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.

J Cancer Res Clin Oncol 2021 Jul 13. Epub 2021 Jul 13.

Department of Pediatrics, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.

Purpose: Hepatic sinusoidal obstruction syndrome (SOS) represents a serious complication following hematopoietic stem cell transplantation (HSCT). Our study aimed to investigate important risk factors of SOS in a pediatric population.

Methods: This retrospective study analyzed 105 children, adolescents and young adults who underwent allogeneic HSCT at our pediatric HSCT center in Jena. The observation period was 12 years and SOS was defined by the pediatric criteria of the European Society for Blood and Marrow Transplantation (EBMT).

Results: 15 out of all 105 patients developed SOS (14.3%). The median time from HSCT to SOS diagnosis was 12 days. The mortality rate of SOS was 20.0%. In univariate analyses, we identified the significant risk factors of patient age < 1 year [odds ratio (OR) = 7.25, p = 0.037], prior treatment with gemtuzumab ozogamicin (OR = 11.00, p = 0.020), high pretransplant ferritin levels above 1500 ng/mL (OR = 4.00, p = 0.033), 2000 ng/mL (OR = 4.69, p = 0.016), and 2400 ng/mL (OR = 5.29, p = 0.005) as well as international normalized ratio (INR) ≥ 1.3 (OR = 5.91, p = 0.009). The following risk factors could be confirmed in multivariate analysis: treatment with gemtuzumab ozogamicin (OR = 9.24, p = 0.048), ferritin > 2400 ng/mL (OR = 5.74, p = 0.023), and INR ≥ 1.3 (OR = 8.02, p = 0.007).

Conclusion: Our study confirms several risk factors from the current literature. Additionally, this is the first report on the risk factor of high pretransplant INR.
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http://dx.doi.org/10.1007/s00432-021-03732-1DOI Listing
July 2021

Interleukin-10-592 polymorphism: impact on relapse and survival after allogeneic hematopoietic stem cell transplantation in children with hematological malignancies.

J Cancer Res Clin Oncol 2021 Jun 21. Epub 2021 Jun 21.

Department of Pediatrics, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.

Purpose: Interleukin-10 (IL-10) potentially can promote the development of alloimmunity. The aim of this study was to investigate if the IL-10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT) and if that has an impact on event-free survival (EFS) and overall survival (OS).

Methods: A cohort of 211 children with acute lymphoblastic leukemia (n = 99), acute myeloid leukemia (n = 69), myelodysplastic syndrome (n = 31) or chronic myeloid leukemia (n = 12) who underwent hematopoietic stem cell transplantation (HSCT) in a single center and their respective donors were genotyped of IL-10 gene for rs1800872 using TaqMan real-time polymerase chain reaction.

Results: The IL-10-592 CC genotype was detected in 107 of the 211 donors (50.7%) and in 106 of the 211 patients (50.2%). Genotype AC was found in 95 donors (45.0%) and in 90 patients (42.7%). Nine donors (4.3%) and 15 patients (7.1%) were homozygous for AA. Ultimately, we observed a significantly reduced incidence of relapse rate (RR) in patients who were transplanted from a donor with the IL-10-592 CC genotype (19% versus 43% (AC) versus 49% (AA); P = 0.0007). In addition, a significant increase of EFS (P = 0.004) and OS (P = 0.006) was detected if the IL-10-592 CC genotype is present in the donor. The occurrence of the IL-10-592 CC genotype, in either donors or recipients, had no significant impact on acute and chronic graft-versus-host disease. In addition, the IL-10-592 genotype of the recipients was not relevant for the RR (P = 0.47434), the EFS (P = 0.840), and the OS (P = 0.535).

Conclusion: The IL-10-592 CC genotype in the donor was associated with a significant decrease of RR which led to a significant increase of EFS and OS after HSCT. This is the first study to describe an association of the IL-10 gene polymorphism with RR, EFS, and OS after HSCT. Selecting a donor with the IL-10-592 CC genotype could be a useful therapeutic strategy for improving the outcome after allogeneic HSCT.
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http://dx.doi.org/10.1007/s00432-021-03695-3DOI Listing
June 2021

Association of recipient and donor interleukin 6 polymorphisms 174 and 597 with outcome after allogeneic hematopoietic stem cell transplantation in children.

J Cancer Res Clin Oncol 2021 Jun 12. Epub 2021 Jun 12.

Department of Pediatrics, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.

Purpose: The success of allogeneic hematopoietic stem cell transplantation (HSCT) is compromised by complications such as infection, relapse, and graft-versus-host disease (GVHD). The investigation of non-HLA immunogenetics, particularly of cytokines, could identify predictors of an unfavorable outcome after allogeneic HSCT. In this study, we examined the impact of single nucleotide polymorphisms (SNPs) within the promoter region of interleukin 6 (IL6) on the development of GVHD after pediatric allogeneic HSCT.

Methods: In this retrospective analysis, we included 320 pediatric patients with a median age of 10 years who underwent an allogeneic HSCT and their respective donors. We used TaqMan real-time polymerase chain reaction to analyze the SNPs IL6-174 (G/C) and IL6-597 (G/A). The IL6-174 polymorphism was examined in 300 recipients and 295 donors. The IL6-597 polymorphism was analyzed in 299 recipients and 296 donors. We investigated the influence of the IL6-174 and IL6-597 polymorphisms on overall survival, event-free survival, relapse incidence, transplant-related mortality, and the occurrence of GVHD.

Results: G polymorphism at position 174 of the recipient IL6 gene was associated with a higher incidence of acute GVHD (GG vs. GC/CC; P = 0.024). Patients with IL6-597 GG genotype developed acute GVHD more frequently than individuals with an A allele (GG vs. GA vs. AA; P = 0.013). IL6-174 GG homozygous recipients had a more frequent occurrence of chronic GVHD (GG vs. GC/CC; P = 0.049). We observed a significant increased risk of chronic GVHD in recipients with IL6-597 GG genotype (GG vs. GA vs. AA; P = 0.043). Polymorphisms of donors did not affect the incidence of acute GVHD and chronic GVHD. In multivariate analysis, the IL6-174 and IL6-597 SNPs were independent significant risk factors for acute GVHD (P = 0.030; P = 0.007, respectively) as well as for chronic GVHD (P = 0.045; P = 0.015, respectively). In addition, older age at time of transplantation turned out to be a significant risk factor for chronic GVHD (P = 0.003).

Conclusion: Our study identified the IL6-174 and IL6-597 GG genotypes of pediatric allogeneic HSCT recipients as genetic risk factors for the development of acute GVHD and chronic GVHD. After evaluations in further studies, these findings could implicate the adjustment of prophylactic measures to reduce the occurrence of acute GVHD and chronic GVHD.
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http://dx.doi.org/10.1007/s00432-021-03677-5DOI Listing
June 2021

Two Cases of Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Thioguanine Treatment for Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2021 Apr 21. Epub 2021 Apr 21.

Department of Pediatrics Section of Pediatric Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation conditioning or high-dose chemotherapy. The underlying pathogenesis involves toxic injury to hepatocytes and sinusoidal endothelial cells. Presenting symptoms include ascites, weight gain, hepatomegaly, and hyperbilirubinemia. Severe VOD/SOS with multiorgan failure has a mortality rate of >80% if left untreated. Thioguanine, a chemotherapy drug used to treat acute lymphoblastic leukemia, has been shown to cause VOD/SOS. Here, we describe cases of 2 patients who developed very severe VOD/SOS after starting thioguanine for acute lymphoblastic leukemia; both achieved complete remission with defibrotide and experienced no defibrotide-related adverse events.
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http://dx.doi.org/10.1097/MPH.0000000000002172DOI Listing
April 2021

Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

JAMA 2021 03;325(9):843-854

Charité-Universitätsmedizin Berlin, Berlin, Germany.

Importance: Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

Objective: To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant.

Design, Setting, And Participants: In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, <5% blasts) or with M2 marrow (blasts ≥5% and <25%) at randomization.

Intervention: Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation.

Main Outcomes And Measures: The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events.

Results: A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P < .001; hazard ratio [HR], 0.33 [95% CI, 0.18-0.61]). Deaths occurred in 8 patients (14.8%) in the blinatumomab group and 16 (29.6%) in the consolidation chemotherapy group. The overall survival HR was 0.43 (95% CI, 0.18-1.01). Minimal residual disease remission was observed in more patients in the blinatumomab vs consolidation chemotherapy group (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). No fatal adverse events were reported. In the blinatumomab vs consolidation chemotherapy group, the incidence of serious adverse events was 24.1% vs 43.1%, respectively, and the incidence of adverse events greater than or equal to grade 3 was 57.4% vs 82.4%. Adverse events leading to treatment discontinuation were reported in 2 patients in the blinatumomab group.

Conclusions And Relevance: Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up.

Trial Registration: ClinicalTrials.gov Identifier: NCT02393859.
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http://dx.doi.org/10.1001/jama.2021.0987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926287PMC
March 2021

Successful Use of Eltrombopag in a Young Child With Chronic Immune Thrombocytopenia.

Cureus 2021 Jan 15;13(1):e12723. Epub 2021 Jan 15.

Department of Pediatrics, Münster University Hospital, Münster, DEU.

The disease course in a young girl with chronic immune thrombocytopenia (ITP) at the initial age of 19 months, treated with eltrombopag, was evaluated retrospectively and is presented as a case record and discussed against the background of the available literature. A stable response and reduction in clinical symptoms, over several years and without frequent dose changes, was achieved. Bleeding symptoms were mild to moderate and occurred particularly frequently in combination with low platelet counts. Raising the platelet count, in turn, was accompanied by a decreased bleeding tendency. Eltrombopag was tolerated well. No new safety signals were observed during the treatment. Based on a follow-up of more than 2.5 years, our case confirms that a child with chronic ITP can benefit from treatment with eltrombopag in the regular care setting. We assume that early treatment with a thrombopoietin receptor agonist could save many children from repeated and lengthy hospitalizations with intravenous immunoglobulins and prolonged administration of corticosteroids.
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http://dx.doi.org/10.7759/cureus.12723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883557PMC
January 2021

Risk factors for mixed chimerism in children with hemophagocytic lymphohistiocytosis after reduced toxicity conditioning.

Pediatr Blood Cancer 2020 09 3;67(9):e28523. Epub 2020 Jul 3.

Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg, Hamburg, Germany.

Background: Reduced toxicity conditioning for hematopoietic stem cell transplantation of patients with hemophagocyticlymphohistiocytosis (HLH) results in favorable survival, however at the expense of relevant rates of mixed chimerism. Factors predisposing to mixed chimerism remain to be determined.

Procedure: Patients with primary HLH transplanted 2009-2016 after treosulfan- or melphalan-based conditioning regimens were analyzed in a retrospective multicenter study for survival, engraftment, chimerism, and adverse events. Mixed chimerism was considered substantial if < 25% donor chimerism occurred and/or if secondary cell therapy was administered. Donor type, graft source, type of alkylating agent, type of serotherapy, and remission status were analyzed as potential risk factors in a multivariable logistic regression model.

Results: Among 60 patients, engraftment was achieved in 95%, and the five-year estimated overall survival rate was 75%. Prevalence of any recipient chimerism was 48%. Substantial recipient chimerism was recorded in 32% of patients. Secondary post-HSCT cell therapy was administered in 30% of patients. A human leukocyte antigen (HLA)-mismatched donor (< 10/10) was the only significant risk factor for the occurrence of substantial recipient chimerism (P = 0.01; odds ratio, 5.8; CI 95%, 1.5-26.3).

Conclusion: The use of an HLA-matched donor is the most important factor to avoid substantial recipient chimerism following treosulfan -or melphalan-based conditioning in primary HLH.
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http://dx.doi.org/10.1002/pbc.28523DOI Listing
September 2020

Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection.

Eur J Clin Microbiol Infect Dis 2020 Aug 27;39(8):1581-1592. Epub 2020 May 27.

Institute of Infection Medicine, Christian-Albrechts-Universität zu Kiel and University Medical Center Schleswig-Holstein, Brunswiker Straße 4, D-24105, Kiel, Germany.

Respiratory tract infections (RTI) can take a serious course under immunosuppression. Data on the impact of the underlying pathogens are still controversial. Samples from the upper (n = 322) and lower RT (n = 169) were collected from 136 children and 355 adults; 225 among them have been immunocompromised patients. Exclusion criteria were presence of relevant cultivable microorganisms, C-reactive protein > 20 mg/dl, or procalcitonin > 2.0 ng/ml. Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Viral/bacterial genome equivalents were detected in more than two-thirds of specimens. Under immunosuppression, herpesviruses (EBV 30.9%/14.6%, p < 0.001; CMV 19.6%/7.9%, p < 0.001; HSV-1: 14.2%/7.1%, p = 0.012) were frequently observed, mainly through their reactivation in adults. Immunocompromised adults tended to present a higher RSV prevalence (6.4%/2.4%, p = 0.078). Immunocompetent patients were more frequently tested positive for IV (15.0%/5.8%, p = 0.001) and M.p. (6.4%/0.4%, p < 0.001), probably biased due to the influenza pandemic of 2009 and an M.p. epidemic in 2011. About 41.8% of samples were positive for a single pathogen, and among them EBV (19.9%) was most prevalent followed by HRV (18.2%) and IV (16.6%). HSV-2 and C.p. were not found. Marked seasonal effects were observed for HRV, IV, and RSV. Differences in pathogen prevalence were demonstrated between immunocompetent and immunocompromised patients. The exact contribution of some herpesviruses to the development of RTI remains unclear.
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http://dx.doi.org/10.1007/s10096-020-03878-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253234PMC
August 2020

Prevalence and dynamics of clonal hematopoiesis caused by leukemia-associated mutations in elderly individuals without hematologic disorders.

Leukemia 2020 08 26;34(8):2198-2205. Epub 2020 May 26.

Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.

Clonal hematopoiesis is frequently observed in elderly people. To investigate the prevalence and dynamics of genetic alterations among healthy elderly individuals, a cohort of 50 people >80 years was genotyped for commonly mutated leukemia-associated genes by targeted deep next-generation sequencing. A total of 16 somatic mutations were identified in 13/50 (26%) individuals. Mutations occurred at low variant allele frequencies (median 11.7%) and remained virtually stable over 3 years without development of hematologic malignancies in affected individuals. With DNMT3A mutations most frequently detected, another cohort of 160 healthy people spanning all age groups was sequenced specifically for DNMT3A revealing an overall mutation rate of 6.2% (13/210) and an age-dependent increase of mutation prevalence. A significant difference (p = 0.017) in the DNMT3A expression pattern was detected between younger and healthy elderly people as determined by qRT-PCR. To evaluate the selection of clonal hematopoietic stem cells (HSCs), bone marrow of two healthy individuals with mutant DNMT3A was transplanted in a humanized mouse model. Xenografts displayed stable kinetics of DNMT3A mutations over 8 months. These findings indicate that the appearance of low-level clones with leukemia-associated mutations is a common age-associated phenomenon, but insufficient to initiate clonal selection and expansion without the additional influence of other factors.
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http://dx.doi.org/10.1038/s41375-020-0869-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387320PMC
August 2020

Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis.

Blood Adv 2020 05;4(9):1998-2010

Department of Immunology. Hematology, Oncology and SCT, University Children's Hospital, Zurich, Switzerland.

Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation-approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti-T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.
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http://dx.doi.org/10.1182/bloodadvances.2020001748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218427PMC
May 2020

Favorable outcomes of hematopoietic stem cell transplantation in children and adolescents with Diamond-Blackfan anemia.

Blood Adv 2020 04;4(8):1760-1769

Robert Debré Hospital, Groupe Hospitalier, Assistance Publique-Hôpitaux de Paris Nord, Université de Paris, Paris, France.

Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia associated with congenital abnormalities and cancer predisposition. Allogeneic hematopoietic stem cell transplantation (HSCT) can correct the hematological phenotype and is indicated in transfusion-dependent patients. In 70 children reported to the German DBA and French HSCT registries, HSCT was performed from 1985 to 2017. Median age at HSCT was 5.5 years (range, 0.9-17.3 years). Two-thirds of patients (64%) were transplanted from a matched sibling donor (MSD), and most procedures were performed after the year 1999 (73%). Primary engraftment was achieved in all patients. One patient developed secondary graft failure. Cumulative incidence of acute graft-versus-host disease (GVHD) was 24% for °II-IV (95% confidence interval [CI], 16% to 37%) and 7% for °III-IV (95% CI, 3% to 17%); cumulative incidence of chronic GVHD was 11% (95% CI, 5% to 22%). The probability of chronic GVHD-free survival (cGFS) was 87% (95% CI, 79% to 95%) and significantly improved over time (<2000: 68% [95% CI, 47% to 89%] vs ≥2000: 94% [95% CI, 87% to 100%], P < .01). cGFS was comparable following HSCT from a MSD and an unrelated donor (UD). Of note, no severe chronic GVHD or deaths were reported following MSD-HSCT after 1999. The difference of cGFS in children transplanted <10 years of age compared with older patients did not reach statistical significance (<10 years: 90% [95% CI, 81% to 99%] vs 10-18 years 78% [95% CI, 58% to 98%]). In summary, these data indicate that HSCT is efficient and safe in young DBA patients and should be considered if a MSD or matched UD is available. HSCT for transfusion dependency only must be critically discussed in older patients.
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http://dx.doi.org/10.1182/bloodadvances.2019001210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189291PMC
April 2020

Yoga in school sports improves functioning of autonomic nervous system in young adults: A non-randomized controlled pilot study.

PLoS One 2020 13;15(4):e0231299. Epub 2020 Apr 13.

Institute of Innovative Health Technologies IGHT, Ernst-Abbe-Hochschule Jena, Jena, Germany.

Background: Yoga in school is a beneficial tool to promote the good health and well-being of students by changing the way they react to stress. The positive effects of yoga-taught in schools-on children, youth and young adults have been demonstrated in former studies using mostly subjective psychometric data.

Aim: The present trial aims to evaluate the potential effects of yoga on autonomic regulation in young adults by analyzing heart rate variability (HRV).

Methods: This study is a non-randomized, explorative, two-arm-pilot study with an active control group. Fourteen healthy young adults took part in a 10-week yoga program (90 min once a week) in school and were compared to a control group of 11 students who participated in conventional school sports (90 min once a week over 10 weeks). 24-hour electrocardiograms (ECGs) were recorded at baseline and following the 10-week intervention. From 20-minute of nocturnal sleep phases, HRV parameters were calculated from linear (time and frequency domain) and nonlinear dynamics (such as symbolic dynamics and Poincaré plot analysis). Analyses of variance (ANOVA) followed by t-tests as post-hoc tests estimating both statistical significance and effect size were used to compare pre-post-intervention for the two groups.

Results: The statistical analysis of the interaction effects did not reveal a significant group and time interaction for the individual nocturnal HRV indices. Almost all indices revealed medium and large effects regarding the time main effects. The changes in the HRV indices following the intervention were more dramatic for the yoga group than for the control group which is reflected in predominantly higher significances and stronger effect sizes in the yoga group.

Conclusion: In this explorative pilot trial, an increase of HRV (more parasympathetic dominance and overall higher HRV) after ten weeks of yoga in school in comparison to regular school sports was demonstrated, showing an improved self-regulation of the autonomic nervous system.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231299PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153865PMC
July 2020

Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies.

Bone Marrow Transplant 2020 10 20;55(10):1996-2007. Epub 2020 Mar 20.

Great Ormond Street Hospital, London, UK.

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m/day (7.7%), 12 g/m/day (35.4%), or 14 g/m/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I-IV and 26.6% for grades II-IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.
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http://dx.doi.org/10.1038/s41409-020-0869-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515850PMC
October 2020

Extended Treatment With Mesenchymal Stromal Cells-Frankfurt am Main in a Pediatric Patient With Steroid-refractory Acute Gastrointestinal Graft-Versus-Host Disease: Case Report and Review of the Literature.

J Pediatr Hematol Oncol 2021 04;43(3):e419-e425

Department of Pediatrics, Jena University Hospital, Jena, Germany.

In acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation, there are various options available after the failure of initial steroid therapy. Since the publication of the first study in 2008, mesenchymal stromal cells (MSCs) have also been used with increasing frequency, including in pediatric patients with steroid-refractory aGVHD, and the manufacturing process has undergone further development. MSC-Frankfurt am Main (MSC-FFM, Obnitix), which is manufactured from pooled mononuclear bone marrow cells from 8 donors using a standardized process, resulted in a response rate of 84% in children with steroid-refractory aGVHD. We report on a 13-year-old female patient with acute myeloid leukemia who received Obnitix as a third-line treatment for gastrointestinal (GI) aGVHD in a life-threatening situation. The patient was initially given a total of 4 Obnitix infusions as per the regulatory approval, with her symptoms improving from day 9 after the first infusion. The second cycle of 4 Obnitix infusions followed due to persistent severe protein-losing enteropathy and resulted in complete remission. A systematic review of the literature on MSC in pediatric patients with steroid-refractory aGVHD confirms that MSC treatment beyond 4 weeks is employed in accordance with treatment protocols or on a case-by-case basis. To summarize, aGVHD activity can be checked endoscopically in patients with persistent GI symptoms and a second Obnitix cycle can then be administered if appropriate, with the goal of achieving complete remission. Future studies should also investigate the potential influence of tissue repair properties as an element in MSCs' efficacy in GI aGVHD.
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http://dx.doi.org/10.1097/MPH.0000000000001758DOI Listing
April 2021

Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia.

Clin Epigenetics 2019 12 10;11(1):188. Epub 2019 Dec 10.

KiTZ Clinical Trial Unit, Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) and Heidelberg University Hospital, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.

Background: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies.

Results: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m/day with weekly dose escalations of 50 mg/m until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m/day was determined (maximum, 580 mg/m/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C. Five patients achieved prolonged disease control (> 12 months) and showed a higher C (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome.

Conclusion: An SDR of 130 mg/m/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker.

Trial Registration: ClinicalTrials.gov, NCT01422499. Registered 24 August 2011.
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http://dx.doi.org/10.1186/s13148-019-0775-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902473PMC
December 2019

Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines.

Placenta 2019 12 12;88:20-27. Epub 2019 Sep 12.

Placenta-Labor, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany. Electronic address:

Introduction: Leukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways.

Methods: Low density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR.

Results: A similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target.

Discussion: Dissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.
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http://dx.doi.org/10.1016/j.placenta.2019.09.005DOI Listing
December 2019

Hematopoietic stem cell transplantation for children with acute myeloid leukemia-results of the AML SCT-BFM 2007 trial.

Leukemia 2020 02 2;34(2):613-624. Epub 2019 Oct 2.

Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Düsseldorf, Düsseldorf, Germany.

AML SCT-BFM 2007 was the first hematopoietic stem cell transplantation (HCT) trial in Germany to comply with the European Clinical Trials Directive, and aimed to standardize pediatric HCT for acute myeloid leukemia (AML) across centers in Germany, Austria, and the Czech Republic. Children with high-risk features and a good early response achieving a complete first remission (CR-1) and those in CR-2 after a first relapse were stratified to receive HCT from a matched donor after myeloablative conditioning consisting of busulfan, cyclophosphamide, and melphalan. Four-year EFS and OS were 61 and 70%. Cumulative incidence of relapse (CIR) was 22%. TRM was 15% and correlated with age reaching 9% (SE 3%) in children younger than 12 years and 31% (SE 9%) in older children and adolescents. Children with poorly responding primary disease or relapse were allocated to receive early HCT after a cytoreductive regimen with fludarabine, amsacrine, and cytarabine, followed by reduced intensity conditioning and prophylactic donor lymphocyte infusions. Four-year EFS and OS were 49 and 53%. CIR was 38% and TRM 11%. For patients with primary poor response disease, early use of RIC HCT followed by prophylactic DLI can induce long-term remissions in more than 50% (EFS 46% (SE 9%)).
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http://dx.doi.org/10.1038/s41375-019-0584-8DOI Listing
February 2020

Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemia-A prospective international multicenter trial on behalf of the BFM-SG and the EBMT-PDWP.

Am J Hematol 2019 08 29;94(8):880-890. Epub 2019 May 29.

St. Anna Kinderspital and Children's Cancer Research Institute (CCRI), Department of Paediatrics, Medical University of Vienna, Vienna, Austria.

Severe infections (SI) significantly impact on non-relapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALL-BFM-SCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period (hazard ratio [HR]: 2.57; P < .001), and with any SI between day +30 and + 100 (HR: 2.91; P = .011). Bacterial (HR: 2.24; P = .041) and fungal infections (HR: 4.06; P = .057) occurred more often in the pre-engraftment phase and viral infections more often before day +30 (HR: 2.66; P = .007) or between day +30 and + 100 (HR: 3.89; P = .002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P < .002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.
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http://dx.doi.org/10.1002/ajh.25511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772138PMC
August 2019

Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL.

Bone Marrow Transplant 2019 11 14;54(11):1847-1858. Epub 2019 May 14.

Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Although allogeneic hematopoietic stem-cell transplantation (HSCT) provides high cure rates for children with high-risk acute lymphoblastic leukaemia (ALL), relapses remain the main cause of treatment failure. Whereas donor killer cell immunoglobulin-like receptor (KIR) genotype was shown to impact on relapse incidence in adult myeloid leukaemia similar studies in paediatric ALL are largely missing. Effect of donor KIR genotype on transplant outcome was evaluated in 317 children receiving a first myeloablative HSCT from an HLA-matched unrelated donor or sibling within the prospective ALL-SCT-BFM-2003 trial. Analysis of donor KIR gene polymorphism revealed that centromeric presence and telomeric absence of KIR B haplotypes was associated with reduced relapse risk. A centromeric/telomeric KIR score (ct-KIR score) integrating these observations correlated with relapse risk (hazard ratio (HR) 0.58; P = 0.002) while it had no impact on graft-versus-host disease or non-relapse mortality. In multivariable analyses ct-KIR score was associated with reduced relapse risk (HR 0.58; P = 0.003) and a trend towards improved event-free survival (HR 0.76; P = 0.059). This effect proved independent of MRD level prior to HSCT. Our data suggest that in children with ALL undergoing HSCT after myeloablative conditioning, donor selection based on KIR genotyping holds promise to improve clinical outcome by decreasing relapse risk and prolonged event-free survival.
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http://dx.doi.org/10.1038/s41409-019-0543-zDOI Listing
November 2019

Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant.

Biol Blood Marrow Transplant 2019 09 11;25(9):1786-1791. Epub 2019 May 11.

St. Anna Children's Hospital, Medical University Vienna, Vienna, Austria.

Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.005DOI Listing
September 2019

Evaluating STAT5 Phosphorylation as a Mean to Assess T Cell Proliferation.

Front Immunol 2019 5;10:722. Epub 2019 Apr 5.

Medical Faculty, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany.

Here we present a simple and sensitive flow cytometric-based assay to assess T cell proliferation. Given the critical role STAT5A phosphorylation in T cell proliferation, we decided to evaluate phosphorylation of STAT5A as an indicator of T cell proliferation. We determined pSTAT5A in T cell treated with either CD3/CD28 or PHA. After stimulation, T cells from adult healthy donors displayed a strong long-lasting phosphorylation of STAT5A, reaching a peak value after 24 h. The median fluorescence intensity (MFI) of pSTAT5A increased from 112 ± 17 to 512 ± 278 (CD3/CD28) (24 h) and to 413 ± 123 (PHA) (24 h), the IL-2 receptor-α (CD25) expression was greatly enhanced and after 72 h T cell proliferation amounted to 52.3 ± 10.3% (CD3/CD28) and to 48.4 ± 9.7% (PHA). Treatment with specific JAK3 and STAT5 inhibitors resulted in a complete blockage of phosphorylation of STAT5A, CD25 expression, and suppression of T cell proliferation. Compared with currently available methods, STAT5A phosphorylation is well-suited to predict T cell proliferation. Moreover, the method presented here is not very time consuming (several hours) and delivers functional information from which conclusions about T cell proliferation can be drawn.
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http://dx.doi.org/10.3389/fimmu.2019.00722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460883PMC
September 2020

Supportive mistletoe therapy in a patient with metastasised neuroblastoma.

BMJ Case Rep 2019 Mar 31;12(3). Epub 2019 Mar 31.

Klinik für Kinder- und Jugendmedizin, Friedrich-Schiller-Universität Jena, Jena, Germany.

Therapies of complementary and alternative medicine (CAM) are used increasingly in paediatric oncology. We present and discuss the influence of supportive mistletoe therapy on factors, such as quality of life, physical ability and performance, and course of disease based on the case of a female patient diagnosed at age 18 with metastasised neuroblastoma, which responded insufficiently to chemotherapy.
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http://dx.doi.org/10.1136/bcr-2018-227652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453412PMC
March 2019

Immunosuppressive Total Nodal Irradiation-Based Reconditioning Regimens After Graft Rejection or Graft Failure in Pediatric Patients Treated With Myeloablative Allogeneic Hematopoietic Cell Transplantation.

Int J Radiat Oncol Biol Phys 2019 05 26;104(1):137-143. Epub 2018 Dec 26.

Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany. Electronic address:

Purpose: This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation.

Methods And Materials: Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors.

Results: After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported.

Conclusions: In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.
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http://dx.doi.org/10.1016/j.ijrobp.2018.12.031DOI Listing
May 2019

Solid organ transplantation after hematopoietic stem cell transplantation in childhood: A multicentric retrospective survey.

Am J Transplant 2019 06 25;19(6):1798-1805. Epub 2019 Jan 25.

Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt am Main, Germany.

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft-vs-host disease in 16 children (36.3%), acute or chronic HSCT-related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow-up was 10.9 years (95% confidence interval: 1.7-29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success.
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http://dx.doi.org/10.1111/ajt.15240DOI Listing
June 2019
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