Adenosine deaminase 2 (ADA2) deficiency is an auto-inflammatory disease due to mutations in cat eye syndrome chromosome region candidate 1 (
) gene, currently named
. The disease has a wide clinical ...spectrum encompassing early-onset vasculopathy (targeting skin, gut and central nervous system), recurrent fever, immunodeficiency and bone marrow dysfunction. Different therapeutic options have been proposed in literature, but only steroids and anti-cytokine monoclonal antibodies (such as tumor necrosis factor inhibitor) proved to be effective. If a suitable donor is available, hematopoietic stem cell transplantation (HSCT) could be curative. Here we describe a case of ADA2 deficiency in a 4-year-old Caucasian girl. The patient was initially classified as autoimmune neutropenia and then she evolved toward an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. The diagnosis of ALPS became uncertain due to atypical clinical features and normal FAS-induced apoptosis test. She was treated with G-CSF first and subsequently with immunosuppressive drugs without improvement. Only HSCT from a 9/10 HLA-matched unrelated donor, following myeloablative conditioning, completely solved the clinical signs related to ADA2 deficiency. Early diagnosis in cases presenting with hematological manifestations, rather than classical vasculopathy, allows the patients to promptly undergo HSCT and avoid more severe evolution. Finally, in similar cases highly suspicious for genetic disease, it is desirable to obtain molecular diagnosis before performing HSCT, since it can influence the transplant procedure. However, if HSCT has to be performed without delay for clinical indication, related donors should be excluded to avoid the risk of relapse or partial benefit due to a hereditary genetic defect.
Bloodstream infections (BSIs) after chemotherapy or hematopoietic stem cell transplantation (HSCT) are a leading cause of morbidity and mortality. Data on 154 BSIs that occurred in 111 ...onco-hematological patients (57 hematological malignancies, 28 solid tumors, and 26 non-malignant hematological diseases) were retrospectively collected and analyzed. Monomicrobial Gram-positive (GP), Gram-negative (GN), and fungal BSIs accounted for 50% (77/154), 38.3% (59/144), and 3.2% (5/154) of all episodes. Polymicrobial infections were 7.8% (12/154), while mixed bacterial-fungal infections were 0.6% (1/154). The most frequent GN isolates were
(46.9%), followed by
(21.9%),
species (18.8%), and
species (6.3%). Overall, 18.8% (12/64) of GN organisms were multidrug-resistant (seven
, three
, and two
), whereas GP resistance to glycopeptides was observed in 1% (1/97). Initial empirical antibiotic therapy was deemed inappropriate in 12.3% of BSIs (19/154). The 30-day mortality was 7.1% (11/154), while the bacteremia-attributable mortality was 3.9% (6/154). In multivariate analysis, septic shock was significantly associated with 30-day mortality (
= 0.0001). Attentive analysis of epidemiology and continuous microbiological surveillance are essential for the appropriate treatment of bacterial infections in pediatric onco-hematological patients.
Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumour of the infancy and the first decade of life. It is locally aggressive and potentially life threatening when associated with consumptive ...coagulopathy, known as Kasabach-Merritt syndrome (KMS). No consensus or guideline for the therapy has been reached because of the lack of prospective trials, and the different standard care suggestions are based on retrospective case series.
We report the case of a 9-month-old male with KHE and KMS in which the initial response, obtained with prednisone and vincristine, was subsequently consolidated and strengthened by long-term treatment with sirolimus, a mTOR inhibitor. A summary of the published data is presented as well.
The inhibition of mTOR pathway represents the most important therapeutic innovation introduced in the last few years for KHE. Our case shows the effectiveness and good tolerance of long-term therapy with sirolimus.
To assess the non-inferiority of pegfilgrastim versus filgrastim in speeding the recovery of polymorphonuclear cells (PMN) in pediatric patients who underwent autologous peripheral blood stem cell ...transplant (PBSCT).
The sample size of this randomized, multicenter, phase III study, was calculated assuming that a single dose of pegfilgrastim of 100 ug/kg was not inferior to 9 doses of filgrastim of 5 ug/kg/day. Randomization was performed by a computer-generated list and stored by sequentially numbered sealed envelopes.
Sixty-one patients, with a median age of 11.5 years, were recruited: 29 in the filgrastim arm and 32 in the pegfilgrastim arm. Twenty percent were affected by lymphoma/leukaemia and eighty percent by solid tumors. The mean time to PMN engraftment was 10.48 days (standard deviation SD 1.57) and 10.44 days (SD 2.44) in the filgrastim and pegfilgrastim arms, respectively. Having fixed a non-inferiority margin Delta of 3, the primary endpoint of non-inferiority was reached. No differences were observed for other secondary endpoints: platelet engraftment, mean time to platelet recovery (28 days vs. 33 days), fever of unknown origin (79% vs. 78%), proven infection (34% vs. 28%), mucositis (76% vs. 59%). After a median follow-up of 2.3 years (95% C.I.: 1.5, 3.3), 20 deaths were observed due to disease progression.
We conclude that pegfilgrastim was not inferior to daily filgrastim in pediatric patients who underwent PBSCT. EU CLINICAL TRIAL REGISTER NUMBER: 2007-001430-14.
Introduction:
Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor frequent in children. Biliary duct localization is extremely rare, but it is the most common cause of malignant ...obstructive jaundice in pediatric patients.
Methods:
This report describes a series of 10 patients under 18 years of age with biliary tract rhabdomyosarcoma who were enrolled, from 1979 to 2004, in 3 consecutive Italian pediatric cooperative protocols that had been drawn up by the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).
Results:
Considering initial and delayed surgery, tumor resection was achieved in 7 cases, 3 complete with free margins (2 liver transplants) and 4 with microscopic residual disease. Chemotherapy was given to all patients and radiotherapy to 3. At present, 5 patients survive in complete remission 90-200 months after diagnosis while 4 died of disease progression or relapse and 1 of liver transplant-related complications.
Conclusions:
Better outcomes in this series were associated with the feasibility of conservative surgery due to the favorable location of the tumor, in particular in the common bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive surgery or liver transplant, which were linked to worse outcomes in our series.
BACKGROUND, OBJECTIVES
The antibody titer of vaccine-preventable disease in 70 patients who underwent chemotherapy or haemopoietic stem cell transplantation (HSCT) was assessed in order to evaluate ...the seroprotection after treatment and the feasibility and the efficacy of a policy of revaccination.
METHODS
Serum antibody titers of 70 patients for hepatitis B (HBV), Rubella, Varicella-zoster (VZV), Measles, Mumps, Polio viruses, Clostridium tetani (C. tetani) and Streptococcus pneumoniae (S. Pneumoniae) were analysed.
RESULTS
After chemotherapy, a lack of protective antibody titers against HBV, Rubella, VZV, Measles, Mumps, Polio viruses, C. tetani and S. Pneumoniae were found in 53%, 45%, 46%, 46%, 43%, 21-26%, 88% and 55% of patients, respectively. In patients who were tested both before and after chemotherapy, the loss of immunity was respectively 39%, 43%, 38%, 42%, 32%, 33%, and 80%. A low number of B-lymphocytes was associated with the loss of immunity against Measles (p=0.04) whereas a high number of CD8+ T-lymphocytes was associated with the loss of immunity against VZV (p=0.03). A single booster of vaccine dose resulted in a seroprotection for HBV, Rubella, VZV, Measles, Mumps, Polio viruses, C. tetani and S. Pneumoniae in 67%, 83%, 80%, 67%, 33%, 100%, 88% and 67% of patients, respectively.
After HSCT, the rates of lack and loss of vaccine immunity differ by the infectious disease considered.
CONCLUSIONS
We confirm that seroprotection for vaccine-preventable disease is affected by treatment for pediatric malignancy. A single booster dose of vaccine might be a practical way to restore vaccine immunity in patients after chemotherapy.
The Diagnostic Pitfalls of Mucormycosis Mauro, Margherita; Lo Cascio, Giuliana; Balter, Rita ...
Mediterranean journal of hematology and infectious diseases,
11/2020, Volume:
12, Issue:
1
Journal Article
Open access
Invasive mucormycosis is a very aggressive fungal disease among immunocompromised pediatric patients caused by saprophytic fungi that belong to the order of the Mucorales.
We describe a case of of
...infection in a 15-year-old child with B-cell-Non-Hodgkin Lymphoma (B-NHL) involving lung, kidney and thyroid that initially was diagnosed as probable aspergillosis delaying the effective therapy for mucormycosis.
This case showed that also the intensive chemotherapy for B-NHL may represent a risk factor for mucormycosis infection. Liposomal amphotericin B and surgery remain the key tools for the successful treatment of this aggressive disease.
Long-term survival for acute lymphoblastic leukemia (ALL) in children improved over the last three decades up to 80-90% of affected patients. Consequently, the quality of life of survivors has become ...increasingly important. This study analyses the clinical features and outcome of 119 children with ALL, focusing on the quality of long-term survival in a subset of 22 patients over 18 years of age. Among this group, the 10-year event-free survival and overall survival were 83.1% (C.I. 74.0-89.2) and 88.4% (C.I. 80.9-93.1), respectively. Treatment related long-term medical complications were reported only in 2 patients (9.1%). Secondary school was completed successfully in 20 of 22 patients (89.9%). The remaining 2 patients were still attending at the time of the analysis. In conclusion, current treatment for ALL is well tolerated and does not compromise significantly the quality of life of survivors.
Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered ...a rare and distinctive but non-diagnostic manifestation of cGVHD and, in the absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes.
We report a case of a 17-months-old child affected by hemophagocytic lymphohistiocytosis who underwent a matched unrelated donor haematopoietic stem cell transplantation (HSCT). She developed severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus.
This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.
Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the ...bone in Italy.
The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan-Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model.
This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58-83%) and 72% (95% CI 57-83%) for patients with localized disease and 38% (95% CI 17-60%) and 21% (95% CI 5-45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01), while patients treated in the last decade had better survival (P = 0.002). In fact, the 5-year OS and PFS for patients diagnosed in the period 2000-2008 were 89% (95% CI 71-96%) and 86% (95% CI 66-94%), respectively.
The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome.
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