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Background: According to retrospective osteosarcoma series, ABCB1/P‐glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk‐adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high‐grade osteosarcoma stratified according to Pgp expression. All patients received high‐dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high‐dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event‐free survival (EFS). A postamendment analysis was performed. Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow‐up was 51 months. For Pgp+ patients, 5‐year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%‐76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5‐year EFS rate was 66.4% (90% CI, 55.6%‐75.1%). Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study. The expression of ABCB1/P‐glycoprotein (Pgp) at diagnosis has been used to stratify patients with high‐grade osteosarcoma. Adjuvant mifamurtide, combined with high‐dose ifosfamide for a poor response to induction chemotherapy, can improve event‐free survival in Pgp+ patients. [ABSTRACT FROM AUTHOR]

Keywords: AML; COVID-19; HSCT; SARS-CoV-2; transplantation EN AML COVID-19 HSCT SARS-CoV-2 transplantation 1657 1659 3 05/11/21 20210501 NES 210501 To the Editor: The coronavirus disease 2019 (COVID-19) pandemic outbreak raised many issues concerning global health policies. Thus, considering high-risk AML and clinical recovery, 1 month later the patient received an additional chemotherapy course, despite her persistently positive SARS-CoV-2 swab. Planned hematopoietic stem cell transplantation in a 17-month-old patient with high-risk acute myeloid leukemia and persistent SARS-CoV-2 infection. [Extracted from the article]

Background and Purpose: Stress‐related catecholamines have a role in cancer and β‐adrenoceptors; specifically, β2‐adrenoceptors have been identified as new targets in treating melanoma. Recently, β3‐adrenoceptors have shown a pleiotropic effect on melanoma micro‐environment leading to cancer progression. However, the mechanisms by which β3‐adrenoceptors promote this progression remain poorly understood. Catecholamines affect the immune system by modulating several factors that can alter immune cell sub‐population homeostasis. Understanding the mechanisms of cancer immune‐tolerance is one of the most intriguing challenges in modern research. This study investigates the potential role of β3‐adrenoceptors in immune‐tolerance regulation. Experimental Approach A mouse model of melanoma in which syngeneic B16‐F10 cells were injected in C57BL‐6 mice was used to evaluate the effect of β‐adrenoceptor blockade on the number and activity of immune cell sub‐populations (Treg, NK, CD8, MDSC, macrophages, and neutrophils). Pharmacological and molecular approaches with β‐blockers (propranolol and SR59230A) and specific β‐adrenoceptor siRNAs targeting β2‐ or β3‐adrenoceptors were used. Key Results: Only β3‐, but not β2‐adrenoceptors, were up‐regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub‐populations including Treg, MDSC, and NK. SR59230A and β3‐adrenoceptor siRNAs increased NK and CD8 number and cytotoxicity, while they attenuated Treg and MDSC sub‐populations in the tumour mass, blood, and spleen. SR59230A and β3‐adrenoceptor siRNAs increased the ratio of M1/M2 macrophages and N1 granulocytes. Conclusions and Implications: Our data suggest that β3‐adrenoceptors are involved in immune‐tolerance, which opens the way for new strategic therapies to overcome melanoma growth. Linked Articles: This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc [ABSTRACT FROM AUTHOR]

Stress plays a role in tumourigenesis through catecholamines acting at β-adrenoceptors including β1 -, β2 - and β3 -adrenoceptors, and the use of β-adrenoceptor antagonists seems to counteract tumour growth and progression. Preclinical evidence and meta-analysis data demonstrate that melanoma shows a positive response to β-adrenoceptor blockers and in particular to propranolol acting mainly at β1 - and β2 -adrenoceptors. Although evidence suggesting that β3 -adrenoceptors may play a role as a therapeutic target in infantile haemangiomas has been recently reviewed, a comprehensive analysis of the data available from preclinical studies supporting a possible role of β3 -adrenoceptors in melanoma was not available. Here, we review data from the literature demonstrating that propranolol may be effective at counteracting melanoma growth, and we provide preclinical evidence that β3 -adrenoceptors may also play a role in the pathophysiology of melanoma, thus opening the door for further clinical assays trying to explore β3 -adrenoceptor blockers as novel alternatives for its treatment. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc. [ABSTRACT FROM AUTHOR]

Keywords: coronavirus disease 2019; COVID-19; SARS-CoV-2; AML; immunosuppression; childhood cancer EN coronavirus disease 2019 COVID-19 SARS-CoV-2 AML immunosuppression childhood cancer e222 e224 3 06/18/20 20200615 NES 200615 Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.[1] Few cases of infection in children with cancer are described; also in these patients, except for one reported case,[2] the disease was largely asymptomatic.[3] Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimise the clinical approach to these cases. An optimised management of COVID-19 is essential, in order to identify and treat patients with a more severe disease course; nevertheless, the resumption of the oncological treatment should remain among our first priorities. Coronavirus disease 2019, COVID-19, SARS-CoV-2, AML, immunosuppression, childhood cancer. [Extracted from the article]

Allogeneic haematopoietic stem cell transplantation ( HSCT) is the only curative option for patients with Diamond Blackfan anaemia ( DBA). We report the transplantation outcome of 30 Italian DBA patients referred to the Italian Association of Paediatric Haematology and Oncology Registry between 1990 and 2012. This is one of the largest national registry cohorts of transplanted DBA patients. Most patients (83%) were allografted after 2000. A matched sibling donor was employed in 16 patients (53%), the remaining 14 patients (47%) were transplanted from matched unrelated donors. Twenty-eight of the 30 patients engrafted. One patient died at day +6 due to veno-occlusive disease without achieving neutrophil recovery and another patient remained transfusion-dependent despite the presence of a full donor chimerism. The 5-year overall survival and transplant-related mortality was 74·4% and 25·6%, respectively. Patients younger than 10 years as well as those transplanted after 2000 showed a significantly higher overall survival and a significantly lower risk of transplant-related mortality. No difference between donor type was observed. Our data suggest that allogeneic HSCT from a related or unrelated donor was a reasonable alternative to transfusion therapy in young and well chelated DBA patients. [ABSTRACT FROM AUTHOR]

This report assessed the results of allogeneic stem cell transplantation (allo-SCT) in 26 patients with Shwachman–Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with ciclosporin ± methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T-cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post-SCT. After a median follow-up of 1·1 years, the transplant-related mortality was 35·5% (95% CI 17–54) whilst the overall survival was 64·5% (95% CI 45·7–83·2). Allo-SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens. [ABSTRACT FROM AUTHOR]