Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers

Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.

A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs

In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

Cardiovascular toxicity of antitumor therapy: effect on myocardial and vascular remodeling

Aim. To study the effect of multiagent chemotherapy on structural and functional vascular, electrophysiological parameters and cardiac hemodynamics in patients with stomach cancer.Material and methods. The study included 3 groups of 25 people: healthy volunteers, those with established cardiac disease (hypertension + coronary artery disease), gastric adenocarcinoma (fluoropyrimidine/platinum-based chemotherapy). Cancer patients before and after chemotherapy courses underwent non-invasive assessment of vascular wall and endothelial dysfunction (videocapillaroscopy, digital photoplethysmography), as well as electrocardiography and echocardiography. Healthy volunteers and cardiac patients were examined once.Results. In cancer patients, even before chemotherapy courses, endothelial dysfunction (ED) (occlusal index, 1,7 (1,4; 1,9), normal values >1,8) and structural vascular disorders (stiffness index, 8,9 m/s (7,7; 9,7), normal values <8 m/s; refractive index, 32,4% (27,5; 37,7), normal values <30%). All above-mentioned parameters significantly worsened after multiagent chemotherapy (progression of ED and vascular wall remodeling: occlusal index, 1,3 (1,2; 1,5) (p<0,0002); stiffness index, 10,3 m/s (9,5; 11,2) (p<0,0001); reflection index, 40,2% (35,5; 43,6) (p<0,001) Decrease in left ventricular ejection fraction and diastolic function was detected. The number of supraventricular and ventricular premature beats during chemotherapy increased 9 and 10 times, respectively (p<0,05).Conclusion. The study for the first time assessed the effect of multiagent chemotherapy on ED, vascular stiffness and cardiac hemodynamics in patients with gastric cancer. A significant aggravation of all endothelial function parameters after treatment has been proven, which requires further study in order to develop criteria for early cardiovascular toxicity.

Chimeric Antigen Receptor T-Cell Therapy: The Light of Day for Osteosarcoma

Osteosarcoma (OS) is the most common malignant bone tumor, arising mainly in children and adolescents. With the introduction of multiagent chemotherapy, the treatments of OS have remarkably improved, but the prognosis for patients with metastases is still poor, with a five-year survival rate of 20%. In addition, adverse effects brought by traditional treatments, including radical surgery and systemic chemotherapy, may seriously affect the survival quality of patients. Therefore, new treatments for OS await exploitation. As a novel immunotherapy, chimeric antigen receptor (CAR) T-cell therapy has achieved encouraging results in treating cancer in recent years, especially in leukemia and lymphoma. Furthermore, researchers have recently focused on CAR-T therapy in solid tumors, including OS. In this review, we summarize the safety, specificity, and clinical transformation of the targets in treating OS and point out the direction for further research.

Characteristics of endoprosthesis replacement of bones and joints in patients with metastatic lesions

The article presents the results of endoprosthesis replacement of joints and bones in 19 patients with bone metastasis. The complications resulted from endoprosthesis replacement of joints and bones in cases of bone metastasis were observed in 4 (21.1 %) patients, and tumor recurrences were observed in 2 (10.5 %) patients. In the preoperative period, 19 patients underwent courses of external beam radiotherapy with a total radiation dose (TRD) of 40 Gray, with a single mediated dose (SMD) of 2–2.5 Gray. Also, all patients received preoperative multiagent chemotherapy treatment cycles depending on the primary source of the tumor, and in cases of hormone-dependent tumors, the patients received hormone therapy. Depending on the specific anatomical and functional changes, special implant designs, tools, and techniques were used, which complemented the standard technique of operations. The basic principles of oncosurgery have been adhered to during endoprosthesis replacement of joints and bones, i.e. standard principles of resection and ablastics, removing en bloc of a biopsy area. In endoprosthesis replacement, a cement type of endoprosthesis fixation was used. For an adequate formation of the muscle envelope of the endoprosthesis, a plastic stage of the ope-ration was performed, which allowed to adequately cover the installed endoprosthesis, and thus, reduce the risk of infectious complications. Both displaced and free vascularized musculocutaneous flaps on microvascular anastomoses were used as plastic material. To limit the contact of the metal part of the endoprosthesis with the surrounding tissues and to reconstruct the tendon ligamentous apparatus, a tube of polyethylene tetraphthalate was used, resected tendon and muscles were sutured to it, which allowed to more fully restore joint action. The functioning of extremity according to the MSTS scale after endoprosthesis replacement of joints ranged from 70 to 92 %, and also the quality of life of patients improved up to 70–75 points.

Disparate Use of Chemoradiation in Elderly Patients With Localized Anal Cancer

Background: The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly among the elderly (age ≥65 years). We sought to compare patterns of care for the treatment of SCCA in elderly versus nonelderly patients. Methods: Data for patients with stages I–III SCCA diagnosed from 2004 through 2015 were obtained from the National Cancer Database. Patients were categorized as having received standard-of-care (SOC) chemoradiation (CRT) with multiagent chemotherapy, non-SOC therapy, palliative therapy, or no treatment. Differences in treatment groups were tested using the chi-square test. We used logistic regression to identify predictors of SOC CRT and multiagent versus single-agent chemotherapy in patients receiving CRT. Propensity score matching was used to compare overall survival (OS) in elderly patients receiving multiagent versus single-agent chemotherapy for those receiving CRT. Results: We identified 9,156 elderly and 17,640 nonelderly patients. A lower proportion of elderly versus nonelderly patients (54.5% vs 65.0%; P<.0001) received SOC CRT than other treatments or no treatment. In multivariate analysis, elderly patients were 38% less likely than nonelderly patients to receive SOC CRT (odds ratio, 0.62; 95% CI, 0.58–0.65; P<.0001). A higher proportion of the elderly were treated with single-agent versus multiagent chemotherapy (16.9% vs 11.8%; P<.0001), which resulted in a >1.5-fold increase in the likelihood of elderly patients receiving single-agent chemotherapy (odds ratio, 1.52; 95% CI, 1.39–1.66) in multivariate analysis. After propensity score matching, 3-year OS was higher in elderly patients who received CRT with multiagent versus single-agent chemotherapy (77.1% vs 67.5%; hazard ratio, 0.78; 95% CI, 0.68–0.89; P=.0002). Conclusions: In this comprehensive study of patients with stages I–III SCCA, elderly patients were less likely than nonelderly patients to receive SOC CRT. The low proportion of elderly patients receiving SOC CRT with multiagent chemotherapy for localized anal cancer suggests that the optimal treatment approach for this vulnerable population remains undefined.

Dilemma in diagnosis and management of rare primary pleural Ewing’s sarcoma with synchronous limited metastatic disease

We present a case of a 34-year-old woman who presented with complaints of fever, cough and dyspnoea of 2 months’ duration. On evaluation, she was diagnosed with a rare entity primary pleural Ewing’s sarcoma with synchronous metastases to mediastinal, supraclavicular nodes and single vertebra. Due to the rarity of this entity and lack of treatment guidelines on extraosseous Ewing’s sarcoma, the patient was managed with a combination of multiagent chemotherapy, surgery and radiotherapy as per standard guidelines for skeletal Ewing’s sarcoma. We present this case to discuss differential diagnoses and management dilemmas encountered on the use of local modalities such as surgery and radiotherapy for control of primary and metastatic sites.