Maria Luisa Moleti

In children with acute leukemia (AL), the mortality rate from Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC-K. pneumoniae carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC-K. pneumoniae may reduce this mortality. We conducted an 8-year (2014–2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC-K. pneumoniae carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy). Successful outcomes (survival from FNE) were observed in 94%; seven were fatal, with four due to infectious causes. KPC-KpBSIs caused 10/112 FNEs, 10/20 g-negative BSIs, and 3 deaths. The mortality rate of KPC-KpBSI was 30%. Active EAT was successful in 97% of the FNEs, compared to 87% with standard EAT. All deaths from KPC-KpBSI occurred in patients who received standard EAT, while none occurred with active EAT. KPC-KpBSI mortality rate with initial inactive treatment was 60%. CAZAVI-based EAT was successful in all FNEs, with a higher success rate without any modification compared to colistin-based EAT, where nephrotoxicity occurred in 14%. Therefore, active EAT, mainly a CAZAVI-based combination, was effective, safe, and associated with low overall and KPC-KpBSI-related mortality.

Despite excellent results in frontline therapy, particularly in pediatric age, refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30– 40%, with longer survival only in transplanted patients. On account of the paucity of data, mostly reporting on small series of patients, with heterogeneous characteristics and salvage treatments, at present it is impossible to draw definitive conclusions on the treatment of choice for this difficult to treat subset of patients. New insights into Burkitt lymphoma/leukemia cell biology have led to the development of new drugs, currently being tested, directed at different specific targets. Herein, we describe the results so far reported in refractory Burkitt lymphoma/leukemia, with standard treatments and hematopoietic stem cell transplant, and we review the new targeted drugs currently under evaluation.

Down syndrome (DS) acute lymphoblastic leukemia (ALL), more frequent in pediatric age than in adulthood, still have a worse outcome compared with non-DS population, mainly due to their intrinsic susceptibility to chemotherapeutic drugs toxicity. Furthermore, in the last years, it has been shown that the overexpression of CRLF2 and a Ph-like signature are relatively more frequent in DS patients. We report a case of a DS patient who developed a Ph-like ALL, 21 years after a first diagnosis of B-ALL, successfully treated with blinatumomab after failure of conventional chemotherapy.

Background: About 300 childhood cancer cases are diagnosed annually at the Children Welfare Teaching Hospital (CWTH) in Baghdad, Iraq, and aproximately 32% are acute lymphoblastic leukemia (ALL). Procedure: We performed a retrospective single-center analysis of 1415 ALL children ranging from 1 to 15 years, diagnosed between January 2000 and December 2016. Patients were divided into three cohorts according to treatment period (2000-2005; 2006-2011; 2012-2016). Treatment protocols were based on three consecutive, modified and locally adapted pediatric UKALL protocols (-97, -2003, -2011); a 7-day steroid pre-phase was introduced for all patients from September 2008. Results: The overall complete remission (CR) rate was 86%. It progressively increased from 80% to 91% in the last study period. Early deaths occurred in 10% of children, decreasing from 12% to 6%, over time. Induction treatment abandonment rate was 3%. Relapse occurred in 23% of children. Toxic deaths and overall treatment abandonment in CR were 8% and 13%, respectively. Remission deaths remained unchanged, while abandonments decreased from 23% to 6% over time. At a median follow-up of 65.3 months, with abandonment considered as an event, the 5-year overall survival and event-free survival were 62.2% and 46.3%, and were statistically influenced by the treatment period. Conclusions: Though pediatric ALL survival in Iraq is still below that observed in high income countries, survival rates have progressively improved. Toxic deaths remain an important cause of failure. Pediatric oncologists fully dedicated to the improvement of patients’ care have significantly contributed to lower rates of early deaths, abandonment and treatment failures.

Autologous stem cell transplantation (auto-HSCT) is a part of the therapeutic strategy for various oncohematological diseases. The auto-HSCT procedure enables hematological recovery after high-dose chemotherapy, otherwise not tolerable, by the infusion of autologous hematopoietic stem cells. Unlike allogeneic transplant (allo-HSCT), auto-HSCT has the advantage of lacking acute-graft-versus-host disease (GVHD) and prolonged immunosuppression, however, these advantages are counterbalanced by the absence of graft-versus-leukemia. Moreover, in hematological malignancies, the autologous hematopoietic stem cell source may be contaminated by neoplastic cells, leading to disease reappearance. In recent years, allogeneic transplant-related mortality (TRM) has progressively decreased, almost approaching auto-TRM, and many alternative donor sources are available for the majority of patients eligible for transplant procedures. In adults, the role of auto-HSCT compared to conventional chemotherapy (CT) in hematological malignancies has been well defined in many extended randomized trials; however, such trials are lacking in pediatric cohorts. Therefore, the role of auto-HSCT in pediatric oncohematology is limited, in both first- and second-line therapies and still remains to be defined. Nowadays, the accurate stratification in risk groups, according to the biological characteristics of the tumors and therapy response, and the introduction of new biological therapies, have to be taken into account in order to assign auto-HSCT a precise role in the therapeutic strategies, also considering that in the developmental age, auto-HSCT has a clear advantage over allo-HSCT, in terms of late sequelae, such as organ damage and second neoplasms. The purpose of this review is to report the results obtained with auto-HSCT in the different pediatric oncohematological diseases, focusing on the most significant literature data in the context of the various diseases and discussing this data in the light of the current therapeutic landscape.

Purpose: To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC-K. pneumoniae in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC-K. pneumoniae. Patients and Methods: A 7-year (2013– 2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC-K. pneumoniae carriers treated with active EAT. Results: Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC-K. pneumoniae infections caused 28/94 FNE (30%) and KPC-K. pneumoniae-BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC-K.pneumoniae-BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013– 1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). Conclusion: KPC-K. pneumoniae infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC-K. pneumoniae-BSI-related mortality.

Background: Brentuximab vedotin (BV) is an antibody drug‐conjugated anti‐CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off‐label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL.Materials and methods: In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow‐up was 2.8 years (range: 0.6–8.9 years).Results: The best response was observed in the 86% of patients; the overall response rate was 66%. The 3‐year progression‐free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non‐nodular sclerosis HL and not transplanted had an increased risk of failure. Overall, 46% of patients had grade 3–4 adverse events that led to BV discontinuation in five of them.Conclusion: In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.

Summary: In high‐income countries (HICs) paediatric aggressive B‐cell lymphomas are curable in about 90% of cases. Much worse results, with cure rates ranging from less than 30% to about 70%, are achieved in low‐ and middle‐income countries (LMICs), where 90% of paediatric non‐Hodgkin lymphomas occur. Low socio‐economic and cultural conditions, the lack of optimal diagnostic procedures, laboratory facilities and adequate supportive care exert a strong negative impact on compliance, treatment delivery, toxicity and, consequently, on the clinical outcome. Published data are scarce, generally originating from single institutions, and are difficult to compare. National and international cooperation projects have been undertaken to reduce the unacceptable gap between HICs and LMICs in the management of children with cancer, by promoting the sharing of knowledge and by implementing adequate local healthcare facilities, with initial promising results. In the present review, we will summarize the results so far obtained in the management of paediatric aggressive B‐cell NHL in LMICs.