Although higher nuclear factor κB (NFκB) expression and activity is observed in preeclamptic placentas, its mechanism of activation is unknown. This is the first study to investigate whether the ...canonical, non-canonical, or atypical NFκB activation pathways may be responsible for the higher activation of NFκB observed in preeclamptic placentas. The study included 268 cases (130 preeclamptic women and 138 controls). We studied the expression of the genes coding for NFκB activators (NIK, IKKα, IKKβ, and CK2α) and inhibitors (IκBα and IκBβ) using RT-PCR in real time. The RT-PCR results were verified on the protein level using ELISA and Western blot. To determine the efficiency of the pathways, the ratios of activator(s) to one of the inhibitors (IκBα or IκBβ) were calculated for each studied pathway. The preeclamptic placentas demonstrated significantly lower IKKα and CK2α but higher IκBα and IκBβ protein levels. In addition, the calculated activator(s) to inhibitor (IκBα or IκBβ) ratios suggested that all studied pathways might be downregulated in preeclamptic placentas. Our results indicate that preeclamptic placentas may demonstrate mechanisms of NFκB activation other than the canonical, non-canonical, and atypical forms. In these mechanisms, inhibitors of NFκB may play a key role. These observations broaden the existing knowledge regarding the molecular background of preeclampsia development.
The aim was to evaluate the incidence, clinical course, and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of ...hematopoietic stem cell. Over a 72‐month period, all‐in 5599 children with cancer: 2441 patients with hematological malignancy (HM) and 3158 with solid tumors (ST), and 971 patients after transplantation: 741 after allogeneic (allo‐HSCT) and 230 after autologous (auto‐HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; P < .001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (P < .001), including 78 (10.5%) patients after allo‐HSCT and 3 (1.3%) after auto‐HSCT. Time to develop AdVI was short, especially after allo‐HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first‐line therapy was cidofovir. None of the cancer patients died due to AdVI, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients, AdVIs are rare and associated with very good prognosis even without specific treatment. However, in allo‐HSCT recipients, disseminated disease with fatal outcome is more likely to occur.
Highlights
Low incidence of HAdV causing less severe infections not requiring antiviral therapy but with satisfactory outcome within cancer patients.
In allo‐HSCT recipients disseminated disease requiring antiviral drugs and at risk of fatal outcome is more likely to occur.
Monitoring for HAdV in all patients, and especially in those who underwent AdVI prior to HSCT or had MD or MMUD‐HSCT, at early posttransplantation period should be recommended.
Transplantation of HLA-disparate hematopoietic stem cells from related donors is an alternative for the treatment of patients lacking an HLA-matched family or unrelated donor. In the cases of a ...single HLA antigen disparity, extensive T-cell depletion (TCD) is not required, yet antithymocyte globulin (ATG) must be administered to prevent GvHD or graft rejection. The major concern after HLA-mismatched transplants remains immune reconstitution. Therefore, we prospectively studied the recovery of lymphocyte subsets among 22 children transplanted from partially HLA-matched family donors. We compared two groups of patients: (1) the TCD group included children (n = 1.3) who received grafts after TCD (MACS) due to an HLA disparity for more than one antigen; (2) The non-TCD group included children with either one HLA-mismatched antigen, n = 7; or more than one disparate antigen (n = 2) who received T-cell-repleted grafts and ATG. The study demonstrated rapid NK cell reconstitution among the TCD group. TCD compromised T-cell reconstitution, thus preventing GvHD, but resulting in a higher incidence of severe infectious complications, graft rejection, and disease relapse. Increasing mixed chimerism required the application of donor T-cell addbacks, thus potentiating the risk of GvHD. Primary graft rejection occurred in eight children, who required further transplants. In the non-TCD group faster T-cell reconstitution (predominantly CD3+CD8+ cells) resulted in a lower rate of relapse and infection, yet a higher rate of GvHD, including two fatal cases. Due to improved immune reconstitution, in spite of an increased risk of GvHD, non-TCD transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors.
Clostridium difficile
infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation ...(HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.
Allogeneic hematopoietic cell transplantation (HCT) in children with myelodysplastic syndrome (MDS) remains a challenge due to the toxic conditioning regimens administered to minimize the risk of ...relapse in the HLA-matched or of graft rejection in the HLA-mismatched settings. In the absence of matched sibling donors, alternative donors such as unrelated and/or partially matched family sources remain risky, yet the only available, options. Herein we report the results of HCT from alternative donors in 14 children with different subtypes of MDS (juvenile myelomonocytic leukemia JMML
n = 9; myelodysplastic syndrome MDS refractory anemia
n = 3; MDS refractory anemia with excess of blasts in transformation
n = 2) transplanted at our institution. The median time from diagnosis to HCT was 9 months (range 4 to 90 months). The variety of HCT types included: unrelated peripheral blood progenitor cell transplantation (PBPCT) (
n = 2), partially matched family donor T-cell–repleted BMT/
PBPCT (
n = 6), and haploidentical T-cell–depleted
PBPCT (
n = 6). Five of 14 patients remain alive at 7 to 37 months posttransplant (including two patients after partially matched family donor BMT, two patients after haploidentical T-cell–depleted-
PBPCT, and one after unrelated-
PBPCT, respectively). The major complications were: primary graft failure in the haploidentical T-cell–depleted-setting or graft-versus-host disease (GvHD) in T-cell–repleted partially matched family or unrelated settings, respectively. Despite the high transplant-related mortality rate in this series, allogeneic HCT from alternative donors remains an interesting solution for children with MDS who lack matched sibling donors. Due to improved immune reconstitution, despite an increased risk of GvHD, T-cell–repleted transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors. Splenectomy prior to HCT may positively affect the posttransplant course in patients with overt splenomegaly for example those afflicted with
JMML.
Background
Hodgkin (HL) and non‐Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%‐30% of lymphoma ...patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second‐line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear.
Objective
The aim of this population‐based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL.
Patients and methods
We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second‐line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally.
Results
Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram‐positives were predominant. The rate of multidrug‐resistant bacteria was high, especially for Gram‐negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection‐related mortality was comparable for each group.
Conclusions
The incidence of IC was comparable during first‐ and second‐line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.
The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 ...pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10(6)/kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.
The main objective of the following work is to present our own material and the ways in which we have dealt with haemorrhagic cystitis (HC) following allogenic bone marrow transplantation in ...children.
From 1994 to 2002, allogenic transplantation of haematopoietic cells was performed in 129 children at the Oncological and Haematological Child Clinic, Wroclaw University of Medicine. The procedure was carried out in patients with neoplastic diseases. In 33 cases, HC symptoms of various intensity were observed. The intensity of the symptoms was evaluated according to Arthur's four-point scale. To confirm the diagnosis USG was carried out in each case. Special attention was given to the ultrasonographic structure of the bladder wall. Cartoni's technique was followed in the examination.
Out of 129 children who underwent allogenic transplantation of haematopoietic cells 33 (20.75 %) revealed HC symptoms. The symptoms occurred between the 2nd and the 124th day after transplantation (mean 29 days). The treatment included antiviral medicines, estrogens, reduction of immunosuppression and mechanical urological procedures. The children diagnosed with 2nd grade disease and higher were catheterised and diuresis was forced by the administration of larger amounts of liquids intravenously. Antihaemorrhagic drugs and vitamin K were also given. Blood was substituted if needed as were blood derivatives. Eighteen children with massive haematuria with clots underwent catherisation with a suprapubic catheter so as to continuously rinse the bladder. In 8 cases tamponade of the bladder occurred. The clots were removed from the bladder during cystoscopy under general anaesthesia. Twelve children died from HC. This amounts to 36 % of all the cases identified as HC and 9 % of all the children who underwent allogenic marrow transplantation.
In conclusion it must be emphasised that HC in children after allogenic transplantation of haematopoietic cells is an extremely severe disease, which, if not cured, is terminal. The decision whether to perform embolisation of internal iliac arteries or to remove the bladder when non-radical methods have been exhausted, is worth considering.
PDF
