[Show abstract][Hide abstract] ABSTRACT: Surgery may improve the control of fungal disease and patient survival. The aim of this study was to report a single-centre experience in using surgery for the treatment of paediatric invasive fungal infection (IFI). From 2001 to 2009, 18 paediatric onco-haematology patients underwent 24 surgical procedures as treatment of IFI. At surgery, severe thrombocytopenia and neutropenia were present in four and one episodes respectively. Complications were one pleural effusion, one pleural effusion and surgical wound infection, one pneumothorax with wound dehiscence and one wound dehiscence. None of them required repeat surgery. The median duration of hospitalisation for four complicated procedures was 11 days, range 3-16, and 7 days, range 2-13, for the 20 uncomplicated procedures. No surgery-related deaths occurred. Fourteen patients resumed chemotherapy after a median of 26 days, range 9-77, whereas nine patients underwent hematopoietic stem cell transplantation after a median of 42 days, range 27-110. At 3 months from IFI, 17 patients were alive (94%) and one patient (6%) died from mycosis; the 3-month overall survival (OS) being 94.4%, CI 66.6-99.2. After a median follow-up of 7.1 years (CI 2.8-7.5), the OS was 54.5%, CI 29.2-74.2. Surgery is a feasible and valuable option in paediatric patients because it is associated with a low incidence of complications and an acceptable delay in resuming the chemotherapeutic plan.
[Show abstract][Hide abstract] ABSTRACT: Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.
British Journal of Haematology 05/2012; 158(2):249-55. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Invasive fungal infections are a frequent complication after intensive chemotherapy. The aims of this prospective study were to describe the use of antifungal therapy and to report which strategy was routinely adopted to guide the introduction of antifungal therapy. A total of 321 febrile episodes in 160 paediatric patients affected by acute leukaemia or non-Hodgkin-lymphoma were investigated. Antifungal therapy was used in 100 of 321 febrile episodes (31%), and classified as empiric in 73 episodes, diagnostic-driven in 25 episodes and targeted in 2 episodes. Switching to a second-line antifungal therapy was needed in 28 of 100 episodes (28%) and was classified as empiric in 10 episodes (36%), diagnostic-driven in 17 episodes (61%) and targeted in 1 episode (4%). In 9 of 28 episodes (32%), switching to a third-line antifungal therapy was performed and was classified as empiric in 2 episodes (22%), diagnostic-driven in 6 episodes (67%) and targeted in 1 episode (11%). Invasive fungal infections was reported in 23 of 100 episodes: confirmed in 4 episodes, probable in 8 episodes, and possible in 11 episodes. Attributable mortality was 2.8%. Antifungal therapy was still used mostly empirically, whereas as fever persisted, its modification was guided by a diagnostic-driven approach.
[Show abstract][Hide abstract] ABSTRACT: An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA) early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT). He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.
[Show abstract][Hide abstract] ABSTRACT: Limited data are available on the use of pegfilgrastim in pediatric patients as a mobilizing agent in association with chemotherapy.
This was a prospective, multicenter, Phase II study to evaluate the safety and efficacy of a single dose of 100 µg/kg pegfilgrastim in mobilizing peripheral blood stem cells (PBSCs) in pediatric patients. The primary endpoint of the study was the percentage of good mobilizers with pegfilgrastim (blood peak of CD34+ cells ≥ 20 × 10(6) /L). The results were compared with a historical control group.
Thirty of 36 recruited patients were classified as good mobilizers (83%). The median value of circulating CD34+ at leukapheresis was 143 × 10(6) /L (range, 20 × 10(6) -1988 × 10(6) /L). No significant adverse effects were associated with the use of pegfilgrastim and no patient was withdrawn from using the drug. A blood peak of 20 × 10(6) /L or more CD34+ was observed in 33 of 36 control patients (92%) and the median CD34+ count at leukapheresis was 158 × 10(6) /kg (range, 28 × 10(6) -4529 × 10(6) /kg; p = 0.7). No significant differences were found between the two groups in terms of toxicity or other variables of mobilization. As at October 2008, 23 patients of the pegfilgrastim group and 32 patients of the filgrastim group underwent autologous transplant. No significant differences were found in terms of early toxicity, myeloid recovery, and Day 100 survival.
A single dose of 100 µg/kg pegfilgrastim was safe and effective for PBSC collection in pediatric patients. We suggest that these results support the use of pegfilgrastim for pediatric patients.
[Show abstract][Hide abstract] ABSTRACT: Invasive fungal infections (IFI) are an important complication in pediatric haematological and oncological patients who undergo intensive chemotherapy for leukemia, solid tumour at advanced stage or relapsed, and hematopoietic stem cell transplantation. The incidence of IFI is lower than bacterial infection but mortality rate remains high. This review is designed to help paediatric oncologists in choosing the appropriate anti-fungal strategy and agents for prophylaxis, empirical, pre-emptive and specific therapy on the basis of published evidence.
[Show abstract][Hide abstract] ABSTRACT: Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy.
[Show abstract][Hide abstract] ABSTRACT: Posttransplant lymphoproliferative disease caused by Epstein-Barr virus (EBV-PTLD) is a severe complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We evaluated whether the modulation of immunosuppression (IS) guided by quantitative polymerase chain reaction for EBV (EBV-PCR) was effective as a first-line therapeutic approach for EBV reactivation.
Eighty-nine pediatric patients who received an HSCT from an unrelated donor were prospectively assessed by quantitative EBV-PCR. The EBV-PCR threshold to modulate IS was set to more than 300 genomic copies (gc)/10 peripheral blood mononuclear cells.
EBV-PCR positivity was observed in 56 (63%) of 89 patients at a median time of 44 days after HSCT. The variables associated with EBV-PCR positivity were bone marrow stem cells (P=0.047) and a lower total dose of nuclear cells reinfused (P=0.03). Thirty-one patients (35%) had more than or equal to 300 gc. IS was withdrawn or reduced in 18 (58%) and 13 (42%) of the 31 patients, respectively. EBV viral load (EBV-VL) less than 300 gc was achieved in 30 of these 31 patients at a median of 25 days. Only 1 (1%) of the 89 patients progressed to EBV-PTLD. The patients with EBV-VL more than 300 gc had a lower incidence of acute graft versus host disease III-IV than patients with EBV-VL less than 300 gc: 13% vs. 36%, P=0.02. No differences in terms of chronic graft versus host disease, overall survival, event-free survival and transplant-related mortality were observed between the two groups.
We conclude that PCR-guided modulation of IS may play a role in early intervention for EBV-PTLD and a prospective, randomized study is needed.
[Show abstract][Hide abstract] ABSTRACT: Aplastic anemia (AA) is rarely described after a diagnosis of autoimmune disease (aID).
To assess the prevalence of prior aID in patients with AA recorded in the registry of the European Group for Blood and Marrow Transplantation (EBMT) and to evaluate treatment and outcome.
1,251 AA patients from 18 EBMT centers were assessed.
Fifty patients (4%) were eligible: 22 males and 28 females with a median age of 46 years at the diagnosis of aID and of 51 years at the diagnosis of AA. Information on the treatment of AA was available in 49 patients: 38 received only immunosuppressive therapy (IST), 8 patients underwent hematopoietic stem cell transplantation (HSCT) - 6 as first-line therapy and 2 after failure of IST - whilst 3 patients had a spontaneous recovery. After a median follow-up of 3.19 years, 32 patients were alive, including 7 of the 8 patients who underwent HSCT. Only 6 of 32 patients who were alive at the last follow-up were receiving IST for AA.
Most cases of AA following aID benefitted from IST or HSCT if a matched donor was available. Further prospective investigation is needed to assess the effects of IST on the outcome of underlying aID.