It is a new and exciting time for acute lymphoblastic leukemia (ALL). While nearly 50 years ago, only one in nine children with ALL survived with chemotherapy, nowadays nearly 90% of children have a ...chance of long-term survival. Adults with ALL, as well as the special category of adolescents and young adult (AYA) patients, are catching up with the new developments seen in children, but still their prognosis is much worse. A plethora of factors are regarded as responsible for the differences in treatment response, such as age, ethnicity, disease biology, treatment regimens and toxicities, drug tolerance and resistance, minimal residual disease evaluation, hematopoietic stem cell transplantation timing and socio-economic factors. Taking these factors into account, bringing pediatric-like protocols to adult patient management and incorporating new agents into frontline treatment could be the key to improve the survival rates in adults and AYA.
Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half ...of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.
Background and aim: Multisystemic inflammatory syndrome in children (MIS-C) is a rare and severe condition associated with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection in ...children with onset approximately 4–6 weeks after infection. To date, the precise mechanism that causes MIS-C is not known and there are many questions related to the etiology, risk factors, and evolution of this syndrome. We aimed to describe the clinical manifestations, treatment methods, and disease evolution and analyze the main risk factors for MIS-C in children hospitalized in our clinic. Material and methods: We performed a retrospective study including children with MIS-C followed-up in the 2nd Pediatric Clinic of the Emergency Clinical Hospital for Children Cluj-Napoca, Romania, for 13 months (November 2020–December 2021). Results: We included in our cohort 34 children (mean age 6.8 ± 4.6 years) who met MIS-C criteria: high and prolonged fever associated with organ dysfunction (heart, lungs, kidneys, brain, skin, eyes, bone marrow or gastrointestinal organs), and autoantibodies and/or polymerase chain reaction positives for SARS-CoV-2. Nineteen patients (55.88%) had a severe form of the disease, with multiorgan failure and shock, and myocardial or respiratory failure. The number of organs affected in the severe forms was significantly higher (more than 6 in 73.70%) than in mild forms (2–3 in 60%). Cardiac dysfunction, hypoalbuminemia, hypertriglyceridemia and hyponatremia were more important in severe forms of MIS-C. These patients required respiratory support, resuscitation with fluid boluses, vasoactive drugs, or aggressive therapy. All patients with mild forms had fully recovered compared to 63.16% in severe forms. The others with severe forms developed long-term complications (dilation of the coronary arteries, premature ventricular contraction, or myocardial fibrosis). Two patients had an extremely severe evolution. One is still waiting for a heart transplant, and the other died (hemophagocytic lymphohistiocytosis syndrome with multiorgan failure). Conclusions: From mild to severe forms with multiorgan failure, shock, and many other complications, MIS-C represents a difficult challenge for pediatricians, who must be aware of the correct diagnosis and unpredictable, possibly severe evolution.
Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, ...signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters’ ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.
A coincidental occurrence of severe haemophilia A and Turner syndrome in a female person is extremely rare (less than 10 cases published). In such challenging cases, a multidisciplinary approach ...based on medicine of precision with full access to genetic and bio-molecular exploration is indispensable. The article presents an eight-year-old girl, with a family history of haemophilia, without significant disease signs (only post-dental extraction bleeding and a shorter stature). Discordantly, however, the investigations revealed a challenging condition: a genotype of 46,X,i(Xq), with an Isochromosome Xq responsible for the Turner syndrome and simultaneously, for the detrimental transformation, interfering with X chromosome inactivation, of an obligate hemophilia carrier into a severe hemophilia case-two distinct and provocative diseases.
Colorectal cancer (CRC) is the third most common cancer in Europe, with an annual increase in incidence ranging between 0.4 and 3.6% in various countries. Although the development of CRC was ...extensively studied, limited number of new therapies were developed in the last few years. Bevacizumab is frequently used as first- and second-line therapy for management of metastatic CRC (mCRC). The aim of this study is to present our experience with using bevacizumab beyond disease progression at different dosage levels in mCRC patients, in terms of overall survival, progression-free survival, time to treatment failure, and toxicities.
We performed a consecutive retrospective analysis of patients with confirmed mCRC who were treated with bevacizumab at "Prof Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania. We included patients who had received bevacizumab as first- or second-line therapy and further stratified them according to the dose administered as a second-line (either standard dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, or double dose of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks-depending on the classical chemotherapy partner). All patients had received bevacizumab beyond progression (BYP) which is defined as continuing bevacizumab administration through second-line treatment despite disease progression. In each group, we evaluated the prognostic factors that influenced survival and treatment outcome.
One hundred and fifty-one (151) patients were included in the study. Themedian age of patients receiving double dose bevacizumab (DDB) and standard dose bevacizumab (SDB) was 58 years (range 41-71) and 57 years (range 19-75), respectively. The median overall survival in the DDB group was 41 months (range 27-49) compared to 25 months (range 23-29) in the SDB group (
= 0.01 log-rank test). First-line oxaliplatin-based treatment was used more frequently regardless of group, while irinotecan-based more frequently used as a second-line treatment (
= 0.014). Both oxaliplatin- and irinotecan-based regimens were found to be suitable partners for BYP. Statistical analysis revealed that dose intensity, primary tumor location, and cumulative exposure to BYP had significant influence on survival.
Doubling the dose of bevacizumab after first progression may improve survival in mCRC patients. Increasing bevacizumab dose intensity could override the prognostic impact of primary tumor location in patients receiving double the dose of bevacizumab after first disease progression.
•Paraneoplastic cerebellar degeneration may precede the diagnosis of cancer.•Early diagnosis of paraneoplastic cerebellar degeneration improve the prognosis.•Treatment includes immunotherapy, ...oncological therapy and supportive therapy.•Paraneoplastic cerebellar degeneration suspected in neurological symptoms in women.
Paraneoplastic neurologic syndromes (PNS) are a rare heterogeneous group of disorders associated with malignancy that can result in significant functional impairment. One syndrome in particular, paraneoplastic cerebellar degeneration (PCD), may be severely disabling. PCD is a rare neurological syndrome, associated with active or subclinical cancer, characterized by acute or subacute onset cerebellar ataxia due to tumor-induced autoimmunity against cerebellar antigens. Treatment of paraneoplastic syndromes is generally unsatisfactory, but early diagnosis and treatment of PCD, which includes neurological treatment, immunotherapy and oncological treatment of associated malignancy, may improve the neurological prognosis. We reported the case of a 59-year-old woman who presented PCD as the first sign of ovarian cancer. Laboratory investigations showed the presence of anti-Yo antibodies in the serum. The brain MRI revealed specific modifications for PCD. After oncological treatment, intravenous immunoglobulin therapy and corticosteroid therapy, the oncological response was satisfactory, but no improvement of the neurologic symptoms was achieved.
BACKGROUND Malignant hypercalcemia is a rare finding in the pediatric population, even more rare in hematological malignancies, such as leukemia. CASE REPORT We present a case of a 6-year-old female ...patient who was diagnosed with acute lymphoblastic leukemia, with secondary hypercalcemia. She started chemotherapy following the IC-BFM ALL2002 protocol with simultaneous calcitonin, diuretics and aggressive hydration for hypercalcemia, and went into complete remission after the induction therapy. After 4 months of chemotherapy, she was diagnosed with relapse associated again with malignant hypercalcemia, and underwent chemotherapy with the relapse protocol. There was no response after the first 2 cycles, so we decided to start her on clofarabine. Due to the severe hypercalcemia and consecutive osteolysis, she developed several bone fractures and needed gypsum immobilization. We started her again on calcitonin, but she developed severe adverse reactions, so we found it necessary to start bisphosphonates, first zoledronic acid intravenously, and afterwards clodronate orally. Consolidation of bone fractures was achieved, but due to prolonged immobilization she developed bedsores, superinfected with Lichtheimia corymbifera. We started posaconazole orally, but she rapidly went into severe sepsis with multiple organ failure. The leukemia showed no response to chemotherapy, progressed rapidly, and the patient died. CONCLUSIONS Malignant hypercalcemia is associated with a poor prognosis in leukemia, and might need a more aggressive therapy.
Vulvar cancers make up just 3% to 5% of all gynecological cancers, and they are most typically found in postmenopausal women. Vulvar cancer distant metastases are uncommon and usually arise late. ...Only six cases of vulvar cancer metastasizing to the heart have been reported in the literature, and none of them included both the left and right ventricles. We describe the case of a 68-year-old patient diagnosed with vulvar cancer arising from lichen sclerosus, initially localized, treated with chemotherapy, surgery, and radiation therapy. Less than two months after the end of the treatment sequence, the patient returned to our clinic with bone pain. Imaging investigations have shown multiple disseminated metastases, but not in the heart at that moment. Chemotherapy was initiated, and after two cycles, the patient developed an arrhythmia (atrial fibrillation with rapid ventricular rate), which was later determined to be caused by cardiac metastases discovered by echocardiography and computed tomography. Vulvar cancer metastatic to the heart represents a rare clinical condition, requiring multidisciplinary care. The case's uniqueness is the biventricular metastasis, which resulted in STEMI despite angiographically normal epicardial coronary arteries.
Infantile hemangioma is one of the most common benign tumors affecting children, with ~10-15% requiring medical treatment. These tumors consist of endothelial cells and stromal components, including ...fibroblasts, pericytes and mast cells. Effects of propranolol treatment in combination with bevacizumab or vincristine on cell growth were compared in the current study using human umbilical vein endothelial cells (HUVECs) and BJ human normal fibroblasts (BJs) to determine potential synergic effects
. Inhibition of cell growth was investigated using MTT assays and cytotoxicity of the drugs in various combinations was expressed as half inhibitory concentration (IC
). Apoptosis was investigated using flow cytometry, with Alexa Fluor 488 and propidium iodide. Propranolol inhibited BJ and HUVEC growth in a dose-dependent manner, with increased response observed in BJs (IC50, 148,32 µg/ml; standard error logIC50, 0.07). Treatment with vincristine induced the strongest growth inhibition in HUVECs (IC50, 17,89 µg/ml; standard error log IC50, 0.07) and BJs (IC50, 24,81 µg/ml; standard error log IC50, 0.08) compared with propranolol (HUVEC IC50, 81,94 µg/ml; standard error log IC50, 0.06; BJ-IC50, 148,32 µg/ml; standard error logIC50, 0.07) or bevacizumab (HUVEC IC50 96,91 µg/ml; standard error log IC50, 0.06; BJ IC50, 182,70 µg/ml; standard error log IC50, 0.09) alone. Bevacizumab was the weakest cytotoxic agent. Combination treatment of vincristine with bevacizumab induced the highest levels of apoptosis in HUVECs compared with all other treatments and triple-drug therapy induced the levels of apoptosis in BJs. Single treatment with vincristine, propranolol or bevacizumab induced apoptosis in BJs and HUVECs. In BJs, triple treatment exhibited the greatest influence on apoptosis, compared with single and dual treatments and in HUVECs, vincristine and bevacizumab combination treatment induced apoptosis to the highest level. The present study offers novel perspectives in drug repurposing studies for the three drugs, particularly in diseases where the pathogenesis is based on healthy endothelial cell proliferation, including hemangiomas.
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