Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.

HIV Screening among Patients with Newly Diagnosed Solid and Hematologic Malignancies in a Tertiary Hospital in the Philippines.

Objectives: This preliminary study determined the prevalence of HIV infection among patients with newly diagnosed solid and hematologic malignancies at the Philippine General Hospital - Cancer Institute. Methods: Adult Filipinos aged 19 years and above with biopsy- or imaging-confirmed malignancy and for chemotherapy, seen at the adult medical oncology and hematology clinic from January to September 2021 were included. Demographic and clinical data were obtained using a questionnaire. Rapid HIV screening was performed using blood extracted via finger prick. Pre- and post-test counselling were conducted. Results: Of the 124 patients included in our study, majority were female (91, 73.4%), and 45 years old and above with a median age of 49 (20 - 74). Majority had solid tumors (121, 97.6%) with breast cancer being the most common (67, 54.0%) followed by colorectal (18, 14.5%), and head and neck cancer (14, 11.3%). Among those with hematologic malignancies, two had acute myelogenous leukemia and one had multiple myeloma. Six patients had AIDS-defining malignancies (NHL, cervical cancer). HIV risk factors and associated conditions were present in 18 patients (14.5%). Ten patients reported prior HIV testing. None of the patients tested positive for HIV. Conclusion: The absence of HIV cases detected in our cohort may be due to the low prevalence of HIV risk factors and associated conditions. At this time, there is insufficient evidence to routinely recommend HIV testing among newly-diagnosed cancer patients. However, physicians are encouraged to offer HIV testing to cancer patients, especially to those with HIV risk factors, given the benefits of early detection and management of HIV.

Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients with COVID-19: The Co-CLARITY Trial.

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

A Pragmatic Approach to Managing Long-Term Adverse Effects in Chronic Myeloid Leukemia Treatment.

PURPOSE OF REVIEW: Long-term outcomes have significantly improved with treatment of chronic myeloid leukemia. With proper treatment, most patients will achieve similar survival rates compared to an age-matched population. Treatment-free remission is not attainable for over half of patients and chronic treatment carries with it unique challenges. We provide a pragmatic approach to the monitoring and management of chronic adverse effects (AEs). RECENT FINDINGS: In the presence of severe or intolerable AEs, switching tyrosine kinase inhibitors (TKIs) is reasonable but is not without risk. Dose reductions can be attempted when response is stable to reduce AE intensity. More frequent molecular monitoring with any change is essential. Treatment strategies must adapt to the personalized treatment goal of each patient. Long-term survival remains good even when response is less than a complete molecular response. Consider risks of new AEs when changing therapy and evaluate for dose reductions when appropriate.

Management of Patients with Lower-Risk Myelodysplastic Neoplasms (MDS).

Myelodysplastic neoplasms (MDS) are a heterogenous group of clonal hematologic disorders characterized by morphologic dysplasia, ineffective hematopoiesis, and cytopenia. In the past year, the classification of MDS has been updated in the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours and the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemia with incorporation of morphologic, clinical, and genomic data. Furthermore, the more comprehensive International Prognostic Scoring System-Molecular (IPSS-M) allows for improved risk stratification and prognostication. These three developments allow for more tailored therapeutic decision-making in view of the expanding treatment options in MDS. For patients with lower risk MDS, treatment is aimed at improving cytopenias, usually anemia. The recent approval of luspatercept and decitabine/cedazuridine have added on to the current armamentarium of erythropoietic stimulating agents and lenalidomide (for MDS with isolated deletion 5q). Several newer agents are being evaluated in phase 3 clinical trials for this group of patients, such as imetelstat and oral azacitidine. This review provides a summary of the classification systems, the prognostic scores and clinical management of patients with lower risk MDS.

The Association Between Inflammation and Immunosuppression: Implications for ICI Biomarker Development.

Evasion of immune destruction is considered one of the hallmarks of cancer. Chronic inflammation can enable immune escape by suppressing immune surveillance and permitting the development of tumors and creating a tumor microenvironment that sustains cancer. This includes generating mechanisms that prevent the effectiveness of anti-tumor treatment including immune checkpoint inhibitor therapy. In this review, we explore the interplay of inflammation and immunosuppression, their effects on the tumor microenvironment, and their implications for immune checkpoint inhibitor therapy particularly in the context of predictive biomarkers for their use.

Revisiting a lower starting dose of alectinib in ALK-Positive non-small cell lung cancer.

We present here a case of ALK-positive lung adenocarcinoma that has been started on Alectinib. Treatment has been initiated at the recommended initial dose, but it subsequently required a dose adjustment following adverse drug events. Alectinib is a second-generation, CNS-active, tyrosine kinase inhibitor used in the treatment of ALK-positive non-small cell lung cancer. Its efficacy as a first-line treatment and as a second-line agent after Crizotinib has been proven across several trials both in terms of overall response rate and progression-free survival. The use of Alectinib is associated with side effects that occasionally lead to treatment discontinuation, interruption, or dose adjustment. Several studies have used two starting doses - 300 mg and 600 mg twice daily - across different populations and have consistently shown efficacy of Alectinib for both treatment doses. Results of these studies have also revealed that body weight, rather than race, affect the pharmacokinetics of Alectinib. Randomized trials have shown that the 600 mg dose is associated with more grade ≥3 adverse events and more changes in treatment in contrast to the 300 mg dose. A lower dose of Alectinib may limit treatment disruptions and dose reductions particularly for specific patient populations-particularly those with a lower body weight.

What Will Keep Me Coming Back to the Clinic: Factors Identified by Filipino Colorectal Cancer Patients Seen at a National Academic Referral Center.

Health-care decisions in the Philippines are widely affected by various factors such as family, community, health-care access, and educational attainment. We designed a questionnaire to evaluate patient views at the University of the Philippines-Philippine General Hospital colorectal multidisciplinary clinic to identify factors that contribute to continued follow-up at the colorectal multidisciplinary clinic. A total of 128 patients, 62% of whom were being treated with curative intent participated in the study. We found that trust in their physicians, presence of family support, and affordability of treatment were factors highly valued by patients consulting at the clinic.

FIP1L1-PDGFRA-Positive Hypereosinophilia Presenting with Bilateral Extracranial Carotid Artery Aneurysms.

OBJECTIVE: To describe a case of an adult female Filipino with hypereosinophilia and bilateral carotid artery aneurysms who subsequently developed bilateral cerebral hemisphere strokes following aneurysm stenting. CASE DESCRIPTION: A 57-year-old female patient with persistent hypereosinophilia presented with progressively enlarging bilateral neck masses, revealed to be carotid artery aneurysms on computed tomography angiography. Following surgical exploration, she later developed right-sided hemiplegia, aphasia, and right hemianopia. Cranial computed tomography revealed infarcts on both middle cerebral artery territories. Bone marrow biopsy and fluorescent in situ hybridization revealed findings suggestive of hypereosinophilic syndrome. She was started on standard aspirin and statin therapy and was discharged sixteen days after the procedure. Partial improvement of neurologic deficits was noted two months later on follow up. Chemotherapy with imatinib was initiated. CONCLUSIONS: This patient's prothrombotic state from FIP1L1-PDGFRA-positive hypereosinophilia may have led to large carotid artery aneurysm formation and intramural thrombosis. This case demonstrates a possible and heretofore undocumented neurovascular sequela of hypereosinophilic syndrome.

Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis.

INTRODUCTION: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients. METHODS: We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs) using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs) were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor. RESULTS/DISCUSSION: A high NLR resulted in worse overall survival (OS) (HR, 1.92; 95% CI, 1.29-2.87; p=0.001) and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38-2.01; p<0.00001) across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer). Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29-2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97-3.44; p=0.06). A high NLR also showed worse OS and PFS across all ICIs (ipilimumab, nivolumab, and unspecified or pooled pembrolizumab and nivolumab; OS: HR, 1.92; 95% CI, 1.29-2.87; p=0.001 and PFS: HR, 1.66; 95% CI, 1.38-2.01; p<0.00001). Subgroup analysis by type of ICI showed similar results. CONCLUSION: A high NLR is associated with poorer outcomes across studies. This shows that NLR has the potential as a readily available prognostic indicator for patients receiving ICI based on available studies. Studies utilizing more stringent design may serve to better determine the utility of this tool.