First Course Of Chemotherapy Research Articles

Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Changes in Psychological Condition during Cancer Chemotherapy.

Psychological disorders are prevalent in cancer patients and their psychological condition can change during cancer chemotherapy and influence their quality of life and adherence to treatment. This prospective observational study enrolled cancer patients undergoing chemotherapy. The enrolled patients were assessed at the start of chemotherapy, after the first course of chemotherapy, and more than 2 months later by themselves and by medical staff using four different items. The cancer patients assessed themselves using the Numerical Rating Scale for Anxiety (NRS-A), Hospital Anxiety and Depression Scale subscale for anxiety (HADS-A) and subscale for depression (HADS-D), and patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). A pharmacist or nurse assessed them using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. This study enrolled 109 patients. The anxiety and depression scores were highest at the start of chemotherapy and declined thereafter. Patients with history of psychiatric disorders or taking psychotropic drugs had higher scores than those without such disorders or treatments (P < 0.05), and tended to maintain these high scores at the second and third HADS-A and -D assessments. The scores assessed by the patients themselves were higher than those assessed by the medical staff. Psychiatric distress scores were highest when commencing chemotherapy and declined thereafter. The patients with history of psychiatric disorders or taking psychotropic drugs kept higher scores of HADS-A and -D during whole chemotherapy courses.

Chemotherapy Primary Dose Reduction in Older Cancer Patients: A Retrospective Cohort

Primary dose reduction (PDR) in the first course of chemotherapy is an empirical practice, commonly used in older population. Patients over 70 years old receiving a first course of chemotherapy for a solid tumor were enrolled. A total of 179 patients were included. Standard dose was used in 69.8% of patients, while 30.2% received PDR of chemotherapy. Only 29.6% received a standardized geriatric assessment. Patients receiving standard doses presented 83.2% of toxicities, while 68% of toxicities were reported in patients receiving PDR. The toxicity rate was significantly decreased in patients treated with reduced first-cycle dose of chemotherapy.

Multiparametric Quantitative MRI Evaluation of Changes in Brain Myelin Content after the First Course of Chemotherapy

Objective. Quantitative assessment of changes in brain myelin content after the first course of chemotherapyMaterials and Methods. T1 and T2 maps as well as myelin water fraction (MWF) and macromolecular proton fraction (MPF) maps, reflecting myelin content, were acquired in 6 patients (mean age — 13.7 ± 2.4 years) before and after the first course of chemotherapy. The study was carried out using on 3T MRI scanner. Statistical data processing was carried out using the GraphPad Prism.Results. MPF and T2 values showed an increase in the thalamus and white matter of the occipital lobes of the brain, while MWF values showed an increase in the cerebellum and a decline in the white matter of the frontal lobes. Significant changes were not found for T1 values.Discussion. According to MWF the structures of the brain which are primarily affected by treatment with toxic drugs — the white matter of the frontal lobes and the cerebellum, were revealed. MWF values decreasing in the white matter of the frontal lobes may indicate the process of demyelination in this area, while increased MWF values in the cerebellum could be caused either by remyelination processes or by incomplete cleansing of myelin residues accumulation by macrophages at the site of degeneration. Conclusion. The results obtained demonstrated high potential of MWF values serve as early changes biomarker of neurotoxicity after the chemotherapy treatment. Along with this, the MPF index, which is more sensitive to cerebral edema, may be a predictor of demyelination.

PGK1 Represents a Therapeutic Target for Pediatric Acute Myeloid Leukemia Via Regulating c-Myc/SLC7A5/mTOR Pathway

Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic stem and progenitor cells characterized by abnormal growth, differentiation blockade, and accumulation of immature myeloblasts, which accounts for 15-20% of pediatric leukemia. Emerging literature has shown that metabolism disorder and their related pathways, play pivotal roles in leukemogenesis and disease progression. Phosphoglycerate kinase 1 (PGK1), an essential enzyme in glycolysis pathway, has been demonstrated to be up-regulated in several malignancies, and was related with tumor stage and poor prognosis. This study aimed to investigate the correlation between PGK1 expression and tumorigenesis of AML, explore the possible underlying mechanism as well as provide a potential therapeutic target for pediatric AML. The research included 64 AML patients and 10 healthy donors recruited from July, 2012 to June, 2020 in Children's Hospital of Soochow University. Expression of PGK1 mRNA in bone marrow of newly-diagnosed AML patients was higher than normal group (p&amp;lt;0.001). Based on median expression of PGK1, 64 patients were divided into PGK1high group (n=32) and PGK1low group (n=32). Patients in PGK1high group had lower complete remission (CR) rate after first course of chemotherapy (65.6% vs 75.0%, p=0.027), overall survival (OS) (53.1%±8.8% vs 84.4%±6.4%, p=0.004) and relapse-free survival (RFS)(63.5%±10.4% vs 90.1%±5.4%, p=0.018). PGK1-knockdown cell lines were constructed to figure out the correlation between PGK1 expression and AML development in vitro. Knockdown of PGK1 inhibited the proliferation, suppressed colony formation and promoted apoptosis of AML cells. In addition, PGK1KD AML cells became more sensitive to Cytarabine (Ara-C) and daunorubicin (DNR). AML model was established by injecting PGK1KD P388-D1 cells of BALB/c mice via tail veins. The results indicated that growth of PGK1KD cells in vivo was significantly suppressed compared to negative control group. Moreover, the median survival time of PGK1 KD group was shorter (10 days vs 13 days, p=0.035). NG52, a newly reported small molecule kinase inhibitor of PGK1, could block glycolysis pathway by suppressing the kinase activity of PGK1. NG52 promoted MV4-11 and Kasumi-1 apoptosis in a dose-dependant manner, and showed synergism with Ara-C and DNR in MV4-11 and Kasumi-1. To identify downstream targets of PGK1, RNA-sequencing analysis was performed in PGK1 KD cell lines. SLC7A5 was found to be the most significant down-regulated gene of differentially expressed genes (DEGs). Meanwhile, c-Myc, p-S6 and p-4EBP1 expression were reduced in PGK1 KD cell lines, indicating that c-Myc/SLC7A5/mTOR pathway was suppressed in PGK1 KD AML cells. We subsequently established SLC7A5 KD cells. Inhibition of proliferation and increased apoptosis was found in SLC7A5 KD cells, which was consistent with the results in PGK1 KD cells. Expression of c-Myc and activation of mTOR pathway were observably decreased in SLC7A5 KD cells, which supported the hypothesis above. We found that SLC7A5 expression level was also higher in AML patients than in healthy donors. In conclusion, our study indicated that PGK1 is a molecular biomarker of poor prognosis and a potential therapeutic target of pediatric AML. Inhibition of PGK1 suppressed progression of AML by regulating c-Myc/SLC7A5/mTOR pathway, providing a promising intervention for AML precision medicine.

Possibilities of prevention of nausea during cytostatic therapy: literature review and clinical cases

Chemotherapy-induced nausea and vomiting (CINV) is a side effect of cancer treatment, affecting up to 40% of patients. Nausea and vomiting are the most dangerous and also the most common side effects among patients undergoing chemotherapy. CINV remains one of the most worrisome syndromes associated with cancer therapy and can lead to dehydration, electrolyte imbalances, malnutrition, and metabolic disorders. Risk factors for developing CINV include the patient’s gender and age, a history of CINV, and the emetogenicity and timing of chemotherapy. Options for preventing CINV are 5-HT3 receptor antagonists (i.e., ondansetron, granisetron, palonosetron) in combination with corticosteroids (i.e., dexamethasone) or additionally in combination with NK1 receptor antagonists (i.e., aprepitant, fosaprepitant, netupitant, rolapitant). Palonosetron is a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The effectiveness of palonosetron for delayed nausea and vomiting is also supported by the results of three randomized trials that demonstrated no side effects of the simplified regimen with palonosetron and single dose dexamethasone for the control of CINV associated with moderately emetogenic chemotherapy or AC regimen. A clinical observation of the treatment of a young patient with breast cancer is given. After the first course of chemotherapy, the patient developed a rather serious complication in the form of vomiting, which required hospitalization for infusion therapy. The above clinical observation demonstrates the effectiveness of palonosetron in neo-adjuvant chemotherapy in a young patient, which made it possible to complete the entire course of treatment. After completion of neo-adjuvant chemotherapy, a radical operation was performed and a complete morphological response was noted.

CD81 and Its Relationship to Treatment Response in Patients With Acute Myeloid Leukemia at a Hospital in Hanoi, Vietnam.

Acute myeloid leukemia (AML) has the proliferation of poorly differentiated immature myeloid cells. New studies on immune markers also consider them as one of the factors that affect the prognosis or the patient's ability to respond to drugs. Our study was designed to determine the rate of remission and mortality, and the ability to respond to drugs in newly diagnosed AML patients withpositive CD81. A total of 50 patients diagnosed with AML (excluding acute promyelocytic leukemia) underwent immunophenotyping analysis using flow cytometry. Following the initial diagnosis, the patients received induction therapy, followed by three cycles of consolidation therapy. The patients were then followed up for a period of six months. The treatment efficacy was assessed at two timepoints: on day 28 after the first chemotherapy course and on day 28 after the fourth chemotherapy course. Out of the 50 newly diagnosed AML patients, 40 (80%) were found to be CD81 positive. This CD81-positive group had a high mortality rate after the first course of chemotherapy (17.5%)and after the fourth course of chemotherapy(52.5%), while no patients died in the CD81-negative group. The CD81-positive group had a worse drug response rate with 22.5% and 18.2% in CD81 positive group versus 30% and 40% in the CD81-negative group achieving complete remission after the first course and fourth course, respectively. The CD81 immunological marker was found to be highly prevalent among AML patients in Vietnam. Overexpression of CD81 in patients with AML is associated with an unfavorable prognosis, characterized by higher mortality rates and poorer treatment response.

Investigation of Oral Mucositis Incidence and Risk Factors in Patients Receiving Chemotherapy

Abstract&#x0D; Purpose: Oral mucositis is a common complication of cancer treatment that may negatively impact the patient’s cancer treatment outcome. This study was done to determine the incidence of oral mucositis development and risk factors in patients receiving chemotherapy. &#x0D; Material and Methods: This prospective cohort study included 150 participants undergoing outpatient cancer chemotherapy. To determine the development of oral mucositis, the participants were evaluated for the first course of chemotherapy (day 0) and the next course of chemotherapy treatment (day 14). ‘Patient Information Form’ and the World Health Organization’ Mucositis Grading Scale’ were used to collect data for the study. Descriptive statistics, chi-squared test, and logistic regression were used to analyze the results. &#x0D; Results: According to oral mucosal assessment, incidence of oral mucositis was 27.3%. The mean onset and the mean recovery of oral mucositis were 4.16 ± 2.13 days and 8.72 ± 2.32 days. The most common oral problems were mouth dryness (53.3%), dental caries (44%), and decreased sense of taste (32%). In the oral mucosal assessment performed on the 14th day, 9 patients were found to be grade 1. Patients with a history of mucositis (OR = 5.76, Cl = 2.33–14.24, p = 0.00) showed a significantly higher incidence of oral mucositis. &#x0D; Conclusion: In this study, the incidence of oral mucositis and risk factors that may affect the development of oral mucositis in patients receiving chemotherapy were investigated. Mucositis history was found as a risk factor in oral mucositis development. Early recovery of oral mucositis after chemotherapy was observed. Therefore, patients should be followed up in the early period after chemotherapy.

Pharmacist Effect on Discharge Follow-Up Education in Pediatric Oncology Outpatient Clinics: A Quality Improvement Study.

We aimed to describe the effect of education provided by a clinical pharmacy specialist at a patient's follow-up appointment after discharge, and to assess caregiver satisfaction. A single-center, quality improvement study was conducted. A standardized data collection tool was created to characterize interventions made by clinical pharmacy specialists during an outpatient clinic appointment scheduled shortly after discharge. Pediatric patients with cancer who met the following criteria were included: 1) initial diagnosis without receiving chemotherapy, 2) first course of chemotherapy after initial diagnosis or relapsed disease, and 3) post-hematopoietic stem cell transplantation or cellular therapy. A survey was provided to families after the follow-up discharge appointment to assess the caregiver's satisfaction of the new process. From January to May 2021, a total of 78 first-time discharge appointments were completed. The most common reason for follow-up was discharge after first course of chemotherapy (77%). The average duration of each appointment was 20 minutes (range, 5-65). The clinical pharmacy specialist made an intervention during 85% of appointments. The most common intervention made during the visit was reinforcement of medications (31%). Thirteen surveys were completed by caregivers; 100% of the caregivers reported the follow-up appointment was helpful. Additionally, they reported the most useful resource provided at discharge was the medication calendar (85%). Investing clinical pharmacy specialist time with patients and caregiver after discharge appears to have a meaningful effect on patient care. Caregivers report this process is helpful in better understanding their child's medications.

The impact of Down syndrome-specific non-malignant hematopoietic regeneration in the bone marrow on the detection of leukemic measurable residual disease.

Detection of measurable residual disease detection (MRD) by flow cytometry after the first course of chemotherapy is a standard measure of early response in patients with acute myeloid leukemia (AML). Myeloid leukemia associated with Down Syndrome (ML-DS) is a distinct form of AML. Differences in steady-state and regenerating hematopoiesis between patients with or without DS are not well understood. This understanding is essential to accurately determine the presence of residual leukemia in patients with ML-DS. A standardized antibody panel defined quantitative antigen expression in 115 follow-up bone marrow (BM) aspirates from 45 patients following chemotherapy for ML-DS or DS precursor B-cell acute lymphoblastic leukemia (B-ALL-DS) with the "difference from normal (ΔN)" technique. When possible, FISH and SNP/CGH microarray studies were performed on sorted cell fractions. 93% of BM specimens submitted post chemotherapy had a clearly identifiable CD34+ CD56+ population present between 0.06% and 2.6% of total non-erythroid cells. An overlapping CD34+ HLA-DRheterogeneous population was observed among 92% of patients at a lower frequency (0.04%-0.8% of total non-erythroid cells). In B-ALL-DS patients, the same CD34+ CD56+ HLA-DRheterogeneous expression was observed. FACS-FISH/Array studies demonstrated no residual genetic clones in the DS-specific myeloid progenitor cells. Non-malignant myeloid progenitors in the regenerating BM of patients who have undergone chemotherapy for either ML-DS or B-ALL-DS express an immunophenotype that is different from normal BM of non-DS patients. Awareness of this DS-specific non-malignant myeloid progenitor is essential to the interpretation of MRD by flow cytometry in patients with ML-DS.

Abstract P5-01-11: Utility of 18F-FDG PET/CT for the prediction of pathologic complete response in axilla to neoadjuvant chemotherapy in breast cancer

Abstract Purpose: To evaluate the value of early FDG-PET (18F-Fluorodeoxyglucose-Positron Emission Tomography) metabolic criteria for prediction of pathologic complete response in axilla (pCRAx) after neoadjuvant chemotherapy (NAC) in breast cancer. Methods: Inclusion criteria were all T-stage breast cancers, non-metastatic, with initial lymph node involvement estimated by PET +/- lymph node biopsy, treated with NAC followed by surgery with axillary lymph node dissection (ALND), managed at the George-François Leclerc Cancer Center in Dijon, France, between 2009 and 2019. A PET was performed before and after the first course of chemotherapy (PET1 and PET2). pCRAx was defined as the absence of invasive cells in the nodes at the time of ALND (i.e. ypN0). The Sataloff classification was used as reference on each pathological report. Patients with a Sataloff NA classification (i.e. evidence of therapeutic effect, and no residual disease) and, if axillary involvement was proven at diagnosis, NB (i.e. no metastasis, no therapeutic effect) were considered as pCRAx. The PET metabolic criteria studied in the axilla were: - SUVmax (Standard Uptake Value) on PET1 and PET2 = fixation in the axillary voxel with the highest activity (kBq/mL)/(injected dose (kBq)/weight (g)) - ΔSUVmax (%) = metabolic response after the first course of NAC = 100 x (SUVmax1 - SUVmax2)/(SUVmax1). Univariate and multivariate analysis were performed to identify factors (clinical, pathologic, metabolic) that may be associated with pCRAx. Relationships between baseline TEP uptake and prognostic parameters were assessed using Receiver Operating Characteristic (ROC) curves. Results: Among 188 patients included, the rate of pathologically proven node involvement was 63.3% (n=119). The pCRAx rate was 45.7% (n=86/188) but varied according to tumor subtypes: 14.5% (n=9/62) of HR(Hormone Receptor)+/HER2-negative, 47.7% (n=21/44) of HR+/HER2-positive, 61.4% (n=27/44) of triple-negative (TN) and 76.3% (n=29/38) of HR-/HER2-positive. Factors significantly associated with pCRAx were by univariate analysis: HER2-positive (HR+ and HR-) and TN subtypes (p&amp;lt; 0.001), SBR (Scarff-Bloom-Richardson) grade (p=0.01), breast pCR (ypT0/is) (p&amp;lt; 0.001), SUVmax2 (p=0.01) and ΔSUVmax (p&amp;lt; 0.001). By multivariate analysis, it persisted the HR-/HER2-positive (p=0.02) and TN (p=0.02) subtypes and breast pCR (p&amp;lt; 0.001). In global population, a decrease in ΔSUVmax of 63% was the optimal threshold to predict pCRAx (Area Under the Curve AUC = 0.73) with a sensitivity (Se) of 51% and specificity (Sp) of 83%. ΔSUVmax remains the best performing parameter in TN (AUC = 0.72; Se at 52%; Sp at 88%). In HR-/HER2-positive patients, SUVmax2 appeared to be a better predictor of pCRAx than ΔSUVmax. A SUVmax2 value of 1.99 was the optimal threshold for predicting pCRAx (AUC = 0.72), yielding a Se of 66% and a Sp of 78%. None of the PET criteria predicted axillary response with sufficient accuracy for HR+ subtypes. Conclusion: PET alone does not appear to be sufficient to predict pCRAx. It seems necessary to use other parameters, whether clinical, biological or imaging, to discriminate responders from non-responders to NAC in order to adapt the subsequent surgical management. Citation Format: ELOISE MICHEL, FRANCOISE BELTJENS, ALEXANDRE COCHET, JEAN LOUIS ALBERINI, CHARLES COUTANT, CLEMENTINE JANKOWSKI. Utility of 18F-FDG PET/CT for the prediction of pathologic complete response in axilla to neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-11.

Early echocardiographic alterations in cancer patients during chemotherapy

Aim. To evaluate the early manifestation of cardiotoxicity after the first course of multiagent chemotherapy (MAC) using echocardiography with an assessment of the left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).Material and methods. The study included 49 cancer patients with elective MAC.Results. After the first administration of a therapeutic dose of chemotherapy, a decrease in LVEF ≥10 and GLS &gt;15 was demonstrated in more than 6,1% of patients, as well as a subclinical decrease in LVEF ≥5% in 22,4% and a decrease in GLS ≥12% in 24,5%.Conclusion. In cancer patients, after the first course of chemotherapy, GLS dynamics should be assessed during echocardiography as a marker of myocardial dysfunction.

Immunotherapy combined with chemotherapy in the treatment for rare primary mucoepidermoid carcinoma of the liver: a case report.

Primary mucoepidermoid carcinoma of the liver (PMCL) is rare in the hepatic system, with no standard treatment and poor prognosis with a median overall survival of only 120 days. PMCL with immunotherapy has not been reported yet. Here, we present a case of PMCL treated by immunotherapy and chemotherapy. A 64-year-old male with PMCL underwent partial right hepatectomy and liver lesion resection on 19 June 2020. Two months later, the chest computed tomography indicated the presence of multiple nodules in both lungs with higher tumor markers. Considering the presence of a tumor metastasis, the patient received four courses of immunotherapy plus mGEMOX chemotherapy from 8 September 2020. The patient tolerated the combined therapy well, with red moles on the face and chest which were considered as grade 1 reactive cutaneous capillary endothelial proliferation. He also had grade 2 thrombocytopenia and leucopenia after the first course of chemotherapy, but no neutropenia, fatigue, vomiting or diarrhea. However, his disease progressed. The patient refused further treatment and died on 20 April 2021. The overall survival time after diagnosis was 301 days. We describe here the first case report on immunotherapy treatment for PMCL. That suggested immunotherapy combined with chemotherapy may be an option after a hepatic lobectomy for PMCL.

Autologous Hematopoietic Cell Transplant Consolidation for First Response Is Associated with Longer Survival in Patients with Nodal Peripheral T-Cell Lymphoma

Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of T-cell lymphoma generally characterized by aggressive behaviors. Nodal PTCL encompasses four major subtypes, PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), ALK-positive (pos) or ALK-negative (neg). The role of autologous hematopoietic cell transplant (auto HCT) during the first response post upfront chemotherapy in nodal-PTCL is still debated. The largest prospective cohort trial (COMPLETE) showed that overall survival (OS) was not statistically different between auto HCT during the first remission compared to nontransplant at the median follow-up of 2.8 years (Park et al. Cancer 2019). This study aims to compare the survival outcomes of patients who received auto HCT to those who did not receive auto HCT during the first response in nodal PTCL. Methods We retrospectively reviewed clinical data on 133 patients at Moffitt Cancer Center who achieved complete response (CR) or partial response (PR) after receiving upfront chemotherapy from 2/2005 to 3/2021. Patients who had stable or progressive disease after the first course of chemotherapy were excluded. Clinical data were abstracted in accordance with institutional review board-approved protocol. Patients were divided into two subgroups: cohort A) patients who received auto HCT during the first response and cohort B) patients who did not receive auto HCT during the first response. The baseline clinical data of two cohorts were summarized using descriptive statistics and compared using Kruskal-Wallis tests for continuous variables and Chi-squared tests for categorical variables. Overall survival (OS) was calculated from the start date of upfront chemotherapy to death or censored to the last follow-up. Median OS (mOS) was calculated using the Kaplan Meier method and compared two cohorts with a log-rank test. Univariate and multivariate COX proportional hazard (PH) analysis was used to evaluate the association of OS. Results Out of 133 patients, 81 (61%) patients were assigned to cohort A. The remaining 52 (39%) patients in cohort B included 30 patients who received auto HCT at CR2 or higher and 22 patients who did not undergo HCT. Of the whole cohort, more than half of the patients (62%) had intermediate-risk diseases based on IPI. The histology subtype included 4% ALK-pos ALCL, 17% ALK-neg ALCL, 48% PTCL-NOS, and 21% AITL. Most patients (83%) in our cohort received CHOP-based therapy upfront and 86% of patients achieved CR after upfront chemotherapy. Clinical characteristics were not significantly different between the two cohorts (table 1). The mOS for patients in cohort A (auto HCT in CR1/PR1) was significantly higher than cohort B (mOS: not reached [95% CI: 60-131 months] for cohort A, and 70 months [95% CI: 39-101 months] for cohort B, p=0.038). The 3-year OS rate in cohort A was 73% as compared to 43% in cohort B (p=0.18). In the univariate analysis, receiving auto HCT during CR1/PR1 was associated with a hazard ratio (HR) of 0.580 (p=0.042). When adjusted for age at diagnosis, sex, histology subtype, types of induction therapy, and response after upfront chemotherapy in the multivariate analysis, receiving auto HCT during CR1/PR1 remained a favorable factor for survival with an HR of 0.52 (p=0.02). Among 26 patients who died in cohort A at the study cut-off time, 14 patients (54%) died from relapsed PTCL post auto HCT. Conclusion Our data showed that auto HCT during the first response was associated with longer survival in transplant-eligible patients with nodal PTCL who achieved CR or PR after first-line chemotherapy. This is despite the fact that 57% of the patients in cohort B received an auto HCT at a later time. Our results highlight a benefit to performing auto HCT during first remission instead of later in the disease course. Large studies are needed to validate our conclusion. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Feasibility of Electronic Patient-Reported Outcome (ePRO) Measurement Using PRO-CTCAE® Questionnaire to Improve Quality of Life Assessment and Healthcare Resources Management in Patients with Lymphoma Receiving Intravenous Chemotherapy

Introduction Different validated questionnaires to assess quality of life (QoL) exist and are used in clinical trials for patients with hematological malignancies. The use of Patient-Reported Outcome Measurement (PROM) in daily clinical practice is scarce. "E-Res Salud” is a value-based healthcare program implemented in a public hospitals network in Spain that aims to give voice to patients and collect individual and aggregate data to improve process management and patient journey. The hypothesis of this prospective single-center study was that the implementation of an electronic PROM (ePROM) program in patients with lymphoma receiving intravenous (iv) chemotherapy in the outpatient setting may improve self-perception of health and allow a better use of resources. The primary objective was to compare the adverse events (AEs) profile reported by physicians in the electronic medical record (EMR) and those reported by patients through a validated questionnaire (PRO-CTCAE®). Secondary objectives were to describe the evolution of symptoms reported along the treatment period and to analyze the impact of a PROM program in the reduction of visits to Emergency Room (ER) and unscheduled hospitalizations. Methods Patients with diagnosis of non-Hodgkin lymphoma (NHL) in the need of iv. therapy between 1st January 2019 and 31st December 2021 were included in the study. "E-Res Salud” was launched in January 2020. Patients included in 2019 and those rejecting participation were considered the control arm. All participating patients were registered in the hospital patient portal. PRO-CTCAE® was electronically sent through the app at 3 points (after 1st, 3rd, and 6th month of therapy). Those reporting symptoms of low intensity were to receive recommendations automatically through the app. Those reporting symptoms of high intensity were to receive a teleconsultation call by the specialized nurse. Differences in proportions were compared with chi-square test. Survival was estimated with Kaplan Meier method. A Sankey diagram was built to depict flows of severity of symptoms. Two-sided test and p-values <0.05 were considered statistically significant. Analysis were performed with SPSS-Statistics.v.23. Results Among the 201 patients included in the study, 76 patients (37.8%) reported outcomes in the ePROM program. Despite patients were not randomized, baseline characteristics were balanced (Table 1). Most frequently AEs reported by physicians in the EMR were hematological (73%), gastrointestinal (62%) and psychological (38%). In contrast, the most frequently patient-reported adverse events were cutaneous (47%), gastrointestinal (44%) and oral (26%), according to PRO-CTCAE® categories (p<0.01). A Sankey diagram showed symptoms’ flow during the first six months of treatment. After the first course of chemotherapy, 46% of patients reported symptoms of high frequency, intensity or impact in their QoL. At third month the proportion of patients reporting high intensity symptoms was significantly higher (67% vs. 46%; p<0.05). No differences were found between the third and sixth month. Differences were also statistically significant between first and sixth month (p<0.01). Finally, those who were adherent to the program had fewer number of visits to ER (19.2% vs. 55.2%; p<0.01) and required fewer unscheduled hospital admissions (15.8% vs. 37.6%; p<0.01). When analyzing outcomes of patients with symptoms of high intensity, the intervention of a specialized nurse reduced the proportion of patients who finally visited the ER vs. those who didn't report any or low intensity symptoms (18.8% vs. 53.8%; p<0.01). Overall survival among patients visiting ER was significantly shorter than among those who did not (stratified hazard ratio, 2.26; 95% confidence interval [CI], 1.11 to 4.63; p=0.025). Conclusion Better understanding of patient-reported symptoms could aid physicians to develop an individualized treatment plan. The use of ePROM and secondarily identifying those patients who report symptoms of high intensity may be translated into a better self-perception of health and QoL. The reduction of ER visits should be a key target for hematologists as it may impact in survival. Further follow-up and larger sample size will allow us to increase data granularity of the level of detail considered in this model and will lead to a decision-making process by integrating patients voice into healthcare decision. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Results of the Treatment of Adolescents and Adults with Acute Lymphoblastic Leukemia with a Pediatric-Inspired Regimen Delivered on an Outpatient Basis: A Single Institution Experience

INTRODUCTION Long-term survival in children with acute lymphoblastic leukemia (ALL) is achieved in around 80%; however, cure rates for adolescents and young adults (AYA) and older adults remain relatively low, at only 40% to 50%. The regimens used in adults are usually less intense than the ones used in their pediatric counterparts, mainly since adults do not tolerate the intensity as well as children do. Different studies have found that adolescents with ALL have a better outcome when treated with pediatric-inspired regimens compared to adult protocols, and other reports suggest improved outcomes for adult patients when treated with ALL pediatric-inspired combination chemotherapy (PICC) regimens. To this effect, we have designed a modification of the St. Jude's TOTAL XI combined chemotherapy program with the goal of delivering it on an outpatient basis. We report here the long-term results of a group of 126 non-pediatric patients with ALL treated with an asparaginase-containing PICC. MATERIAL AND METHODS All consecutive adolescents (12 - 17.9 years), young adults (18 - 24.9 years) and adult (>25 years) patients with ALL diagnosed and treated in the Centro de Hematología y Medicina Interna de Puebla since June 1983 were prospectively included in the study. At diagnosis, the immunophenotype of the malignant cells and the desoxyrribonucleic acid (DNA) content was analyzed by flow cytometry, and cytogenetic markers were also obtained. Patients were treated with a modification of the St. Jude's TOTAL XI PICC regimen, delivered in an outpatient setting. RESULTS A total of 126 patients with ALL (69 AYAs and 57 adults were prospectively enrolled in the study. Median age was 22.5 years (range 12 - 80 years). B-cell lineage was identified in 117 (93%) and T-cell in 9 (7%). At diagnosis, 13 cases (11%) displayed more than 20 x 109/L white blood cells (WBC), 20 (16%) more than 50 x 109/L WBC, while 93 (74%) had less than 20 x 109/L WBC. DNA content was diploid in 69% of cases, hyperploid in 20% and hypodiploid in 11%. Twenty patients (21% of 94 tested) had a BCR::ABL1 rearrangement. The median follow-up was 20 months (range 3 to 326 months). Of the 126 patients enrolled, 5 did not complete the first course of chemotherapy and were lost to follow up. Of the remaining 121 patients, early discontinuation occurred in 5 patients that had complications upon initial therapy and died 3 - 15 days after the diagnosis. Among the remaining 116 patients, 90 (77%) achieved a complete remission (CR) (71% on intention to treat analysis). Chemotherapy was initiated on an outpatient basis in all patients and 24 (20%) had to be admitted in the hospital during the initial 7-week period of the induction / consolidation. Relapses were observed in 38 of the 90 patients who achieved a CR (43%); 13 relapses presented in the CNS and 25 in the BM; two persons had both relapses. The median remission duration for the total cohort was 48 months, while the median overall survival (OS) for the total population was 30 months. CONCLUSION The use of an asparaginase-containing PICC in AYAs and adult patients with ALL renders acceptable results, which are better than those obtained in similar socioeconomic circumstances using adult-oriented treatments, such as Hyper-CVAD. The toxicity of this regimen is acceptable and since it can be delivered on an outpatient basis, it results in diminished costs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Magnetic resonance tomography of the lungs with paramagnetic contrast enhancement in dynamic follow-up control of treatment of lung cancer in radiophobic patient: a case report

Till now the facilities of MRI with paramagnetic contrast enhancement (CE-MRI) in detection of lung tumors remain underused and almost ignored. A clinical case of primary detection and prospective follow-up of lung cancer in a patient whose MRI of the chest revealed a tumor lesion — a central cancer of the left lung, in particular a lesion of the bronchus of the lower lobe of the left lung. MRI of the chest with paramagnetic contrast enhancement was carried out as part of the whole body CE-MRI study after the complex therapy of breast cancer, and both the primary lung tumor and metastatic lesion of mediastinal — subbifurcation lymph nodes were revealed. With a transbronchial biopsy, the diagnosis of lung cancer was verified. Chemotherapy (ChT) was started using the vinorelbin/ carboplatin regimen. After this, the CE-MRI has been carried out during the whole period of followup of anti-cancer chemotherapy. At the CE-MRI during the first course of ChT visually the complete regression of the disease, also with clinical remission was achieved. However, the ChT scheme was not fully completed due to the patient’s departure for urgent private reasons. Two months later, the patient was examined again according to the same CE-MRI protocol, while a relapse of the disease was detected with a more pronounced lesion of the mediastinal lymph nodes than during the initial treatment. ChT with vinorelbine/carboplatin was again carried out under the control CE-MRI, this time completely. According to the chest CE-MRI, visual remission was achieved, with the disappearance of nodular tumor at the site of the previously identified primary tumor of lung cancer and metastatic lesions of lymph nodes. Thus, it was the CE-MRI which provided the early diagnosis and adequate control of treatment of the lung cancer with extensive local lymph nodes spread. After this CE-MRI, the whole body PET with 18F-fluorodeoxyglucose (FDG) was also performed and no signs of relapse or continued tumor growth were revealed. Five months after this stage, the patient did persist to stay completely preserved clinically, at work and socially active. Thus, the chest CE-MRI can be employed for the follow-up of the tumor process in lung cancer, as necessary, without radiation exposure, without limiting the number and frequency of studies.

AML-226 Impairment of Primary Hemostasis as an Additional Risk Factor of Hemorrhage in Patients With Newly Diagnosed Acute Myeloid Leukemia: Ukrainian Prospective Study

Bleeding events in acute myeloid leukemia (AML) are frequent and life threatening, whereas widely used treatment approaches are not always able to satisfy expected outcomes. The primary endpoints were the qualitative and quantitative functions of plasma von Willebrand factor (vWF), which include measurements of vWF activity (vWF:ristocetin cofactor [vWF:RCo]), vWF level (vWF:antigen [vWF:Ag]), factor VIII coagulation activity regarding vWF (vWF:FVIII), and FVIII activity (FVIII) in AML patients. Forty-two patients with newly diagnosed AML (excluding acute promyelocytic leukemia) were included in the study group. The control group included 20 age-matched and sex-matched healthy individuals. The grade (G) of bleeding events was assessed according to the Modified WHO Bleeding Scale (WHO BS). Hemorrhage (G1-4) occurred in 53.3% of patients in the study group during induction therapy. vWF:Ag below normal ranges had been observed in 19% of patients with AML and was associated with the occurrence of severe hemorrhage compared with the patients who had normal vWF:Ag levels and no bleeding episodes (P=0.012). It is important to mention that vWF:Ag levels (median 134, mean 163±18.25) were elevated in most cases (56%) in the main group and are probably associated with a compensatory mechanism for stopping bleeding compared with the control group. In 23.8% of patients with AML, we observed levels of vWF:RCo below normal ranges. Among them, the most frequent bleeding events were G2 (5/10, 50%) and G4 (3/10, 30%); three of them died during the first course of chemotherapy due to gastrointestinal and CNS bleeding. Therefore, we found a statistically significant association between decreased levels of vWF:RCo below normal ranges and the occurrence of severe bleeding episodes (G2-G4) in patients with AML compared with the group that had normal ranges of vWF:RCo and no bleeding events (G0) (P=0.0001). Furthermore, low vWF:FVIII (P=0.033) and FVIII (P=0.037) levels in patients with AML and bleeding episodes G2-G4 had statistical differences compared to non-hemorrhage patients (G0). According to our study, vWF:RCo, vWF:Ag, and vWF:FVIII were associated with hemorrhage in patients with newly diagnosed AML and could be considered predictive factors of bleeding.

The immersive experience of virtual reality during chemotherapy in patients with early breast and ovarian cancers: The patient's dream study.

BackgroundA virtual reality experience (VRE) could represent a viable non-pharmacological intervention to reduce and better manage the main factors of psychophysical distress related to the diagnosis and treatment of cancer.AimThe “Patient’s Dream” study was a two-arm randomized controlled trial conducted at the Regina Elena National Cancer Institute – IRCCS (Rome, Italy) from April 2019 to January 2020 to evaluate VRE impact in patients affected by breast or ovarian cancer. Before starting the first cycle of chemotherapy (CT), patients were randomized to receive the VRE (VRE arm) as “distraction therapy” or to entertain themselves with conventional means (control arm). The primary aims were the assessment of psychological distress, anxiety and quality of life between the two study arms. Secondary endpoints were the perceived time during the first course of CT and the acute and late toxicity.ResultsFourty-four patients were enrolled, 22 patients were randomly assigned to the VRE arm and 22 to the control arm. Collected data underline the absence of prevalent disturbs of anxiety and depression in both groups. Nevertheless, even if the state anxiety values before and after CT decreased in both groups, this reduction was statistically significant over time only in the VRE arm. The duration of therapy perceived by patients undergoing distraction therapy was significantly shorter when compared to the control group. The use of VRE during the first CT cycle appeared to reduce asthenia outcomes.ConclusionObtained data suggest that the VRE positively influenced the levels of state anxiety among cancer patients and support the continuous research on VRE as a distraction intervention, with the aim to meet the clinical need for effective nonpharmacologic adjunctive therapies.Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT05234996, identifier NCT05234996.

Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial

BackgroundAdverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events.MethodsIn this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms.ResultsGeneral linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [− 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy.ConclusionsThis study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events.Trial registrationRetrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).