HALP score as a novel prognostic factor for patients with myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19-84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34-49.88) months by the Kaplan-Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS.

Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Rare side effect caused by atezolizumab, an immune checkpoint inhibitor: Cold agglutinin disease.

INTRODUCTION: Immune checkpoint inhibitors are drugs that are included in the guidelines of hematological and solid cancer treatments, give highly effective results and increase T cell functionality. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. CASE REPORT: A 50-year-old male patient was admitted to an external center with complaints of chest pain and dyspnea. Thoracic CT revealed a 97 × 58 mm mass in the left lung, and a diagnosis of Small Cell Lung Cancer (SCLC) was made by biopsy. The PET/CT performed for staging was also evaluated as extensive stage small cell lung cancer. It was decided to give a combination of atezolizumab and carboplatin-etoposide to the patient.Management and outcome: The patient completed 3 cycles without any problem. Discordance was detected in the hemogram of the patient who came to the control for the assessment of response and had a regression in the imaging. Hemoglobin 9.6 g/dl (N: 14-17.5) hematocrit 14.8% (N: 41-51) were detected in the hemogram. Agglutinins were seen in the peripheral smear performed. Cold agglutinin (+4 positive) and indirect coombs (+3 positive) were found positive. Atezolizumab was stopped and methylprednisolone was started. After 10 days of treatment, discordance improved and methylprednisolone was discontinued by decreasing to half dose every 5 days. DISCUSSION: With the increasing use of immune checkpoint inhibitors, the variety of side effects has increased and case reports have increased. After detection of cold agglutinin, IgG, cryoglobulin, mycoplasma pneumonia, hepatitis B, hepatitis C and HIV were found negative in the differential diagnosis, Our case appears to be immune checkpoint inhibitor-related Cold Agglutinin Disease (CAD). It should not be forgotten that immune checkpoint inhibitors, which are widely used, may cause CAD, and hemoglobin-hematocrit discordance should be paid attention to in routine controls.

Efficacy and Safety of Imatinib Treatment in Elderly Patients With Chronic Myeloid Leukemia: Real-Life Data and a Single-Center Experience.

BACKGROUND: In the era of tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) patients generally live close to a normal lifespan, and the number of elderly patients with CML with comorbidities is increasing. PATIENTS AND METHODS: We retrospectively compared the efficacy and safety of frontline imatinib between elderly patients (≥60 years old) and younger patients (<60 years old) with CML. RESULTS: The study included 33 elderly and 125 younger patients. Elderly patients had significantly higher Charlson comorbidity index (CCI) scores. Efficacy and toxicity were comparable among the older patients with CCI scores of 0 and ≥1. There were significantly more hematologic adverse events (AEs) in elderly patients (P = .005). Although not significant, nonhematologic AEs were also more common in older cases (P = .056). Elderly patients had significantly higher rates of imatinib dose reduction (P < .001). Cumulative response rates were similar in both groups. Event-free survival was comparable, and overall survival (OS)-when non-CML-related deaths were censored-was also similar. In the multivariate analysis, age at diagnosis and CCI were associated with OS, and patients ≥ 60 years of age had a 5.998-times higher risk of death compared with the patients < 60 years of age (P = .011). Similarly, patients with CCI scores ≥ 2 had a 3.758-times higher risk of death compared with patients with a CCI score of 0 (P = .033). CONCLUSIONS: Upfront imatinib was generally well tolerated among elderly Turkish patients with CML with non-inferior responses and long-term outcomes when compared with younger patients. Comorbidities can be problematic in elderly patients, and today the survival of patients with CML is determined mostly by comorbidities.

The Outcomes of Chronic Myeloid Leukemia Patients With Molecular Warning Responses During Imatinib Treatment According to the European LeukemiaNet 2013 Recommendations.

BACKGROUND: In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. PATIENTS AND METHODS: We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. RESULTS: The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. CONCLUSION: It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Outcomes of Chronic Myeloid Leukemia Patients With Early Molecular Response at 3 and 6 Months: A Comparative Analysis of Generic Imatinib and Glivec.

BACKGROUND: The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). PATIENTS AND METHODS: We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). RESULTS: Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. CONCLUSION: The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.

Dasatinib for the treatment of chronic myeloid leukemia: patient selection and special considerations.

Dasatinib is one of the second-generation tyrosine kinase inhibitors used in imatinib resistance and/or intolerance, as well as in the frontline setting in patients with chronic myeloid leukemia-chronic phase, and also in patients with advanced disease. It is also utilized in Philadelphia chromosome-positive acute lymphocytic leukemia. While choosing the appropriate tyrosine kinase inhibitor (ie, dasatinib) for each individual patient, comorbidities and BCR-ABL1 kinase domain mutations should always be taken into consideration, among other things. This review mainly focuses on patient selection prior to dasatinib administration in the treatment of chronic myeloid leukemia.