The Obesity Controversy: Does It Impact Treatment Response in Diffuse Large B-Cell Lymphoma?

Background: We aimed to investigate the association of body mass index (BMI) with treatment response in patients with DLBCL. Material and Methods: Seventy-nine DLBCL subjects were included in this study. Data about patient age, sex, serum LDH level, presence of B symptoms, IPI score, ECOG performance score, disease stage, extranodal involvement, and BMI values at diagnosis were retrieved by retrospective patient record review. Patients were staged according to Ann Arbor classification using CT and/or PET/CT findings, and the presence of B symptoms. Body mass index was calculated by dividing weight in kilograms by height in meters squared (kg/m2). Patients were divided into groups according to their BMI as underweight (BMI≤ 18.5 kg/m2), normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI≥ 30 kg/m2), as defined by the World Health Organization. Results: Patients were divided into four groups according to their BMIs, but because there was only one patient in the underweight group, comparisons were performed between normal-weight, overweight, and obese patients. There was no statistically significant difference between these groups in terms of age, sex, serum LDH level, disease stage, presence of B symptoms, extranodal involvement, ECOG performance score, IPI score and treatment response (p= 0.070, 0.704, 0.325, 0.464, 0.254, 0.152, 0.658, 0.620, and 0.947, respectively). Conclusion: In our study, we showed that BMI has no significant impact on treatment response in patients with DLBCL.

Charlson Comorbidity Index (CCI) in Diffuse Large B-cell Lymphoma: A New Approach in a Multicenter Study.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult lymphomas. The incidence of DLBCL increases with age and has a fairly rapid fatal course without treatment. Patients often have difficulty tolerating standard chemotherapy regimens due to their comorbidities. Charlson Comorbidity Index (CCI), which is calculated by considering 19 different comorbidities, was developed in 1987 and is widely used for mortality prediction in cancer patients. Literature data on CCI and hematological malignancies are limited. Main aim in this study is to evaluate the effectiveness of CCI and compare to the International Prognostic Index (IPI) scoring system in the DLBCL patient group. Methods: A total of 170 patients diagnosed with DLBCL between 1.1.2002- 1.12.2020 were included in the study. Statistical analyzes were performed among patients whose IPI and CCI scores were recorded by considering baseline data. Results: The median age of patients was 58 (range: 17-84). Thirty-five (20.6%) patients had stage III and 76 (44.7%) had stage IV disease. When the CCI, IPI and ECOG scores were compared with the mortality status of the patients as a reference, AUCs were resulted as 0.628 (95% CI: 0.506-0.749), 0.563 (95% CI: 0.484-0.639) and 0.672 (95% CI: 0.596-0.743), respectively. There was no significant difference between the ROC curves of CCI, IPI and ECOG scores. Patients with a CCI score of ≥ 4 had shorter OS comperad to those with a score of < 4. Conclusion: Rather than claiming that CCI is superior to IPI, ECOG or another scoring system in a single-center patient population, it should be stated that CCI is also an effective scoring system in patients diagnosed with DLBCL. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01567-5.

Eltrombopag in the Treatment of Immune Thrombocytopenia: Two-Center Experience from Istanbul.

Immune Thrombocytopenia (ITP) is a disease caused by autoantibodies forming against platelets and T cell dysregulation and is characterized by platelet count falling below 100 × 109/L. Corticosteroids remain as the first-line of treatment, but in the light of recent developments, thrombopoietin receptor agonists are gradually replacing splenectomy in steroid-dependent or refractory patients. In this study, it was aimed to retrospectively evaluate the efficacy, safety and side-effect profile of eltrombopag treatment for chronic ITP. A total of 23 chronic ITP patients treated with eltrombopag from two health institutions in Istanbul were evaluated retrospectively. Overall response rate (partial or complete) was 87%, complete response rate was 78.3%, and the median time from treatment until reaching platelet counts above 50 × 109/L was 14 days (min-max: 4-126). Treatment was discontinued in four patients due to persistent response, two of these were still fully responsive. During treatment, one patient developed basal cell carcinoma, and another developed chronic myelomonocytic leukemia. Although its long-term side effects are not yet known, eltrombopag is a very effective treatment option in ITP and may provide favorable outcomes in patients.

How Does 2016 WHO Criteria for Polycythemia Vera Contribute to Our Daily Practice? A Single-Center Study from Turkey.

Background: We evaluated the frequency of subnormal erythropoietin levels, Janus kinase 2 (JAK2) V617F positivity and polycythemia vera (PV) in patients who did not meet World Health Organization (WHO) 2008 criterion for hemoglobin levels but were suggested to be investigated for PV in 2016 revision. Materials and Methods: We assessed the data of 92 patients who were further evaluated with JAK2V617F mutation and serum erythropoietin (EPO) levels and bone marrow biopsy, if necessary. We also compared this patient group with 20 patients whose Hgb>18.5 g/dL for men and >16.5 g/dL for women. Results: Nine patients (45%) in the higher hemoglobin group were JAK2V617F positive, while 4 patients (4.3%) in the lower hemoglobin group were JAK2V617F positive (p<0.001). The number of patients with serum EPO levels <4.3 mIU/mL was significantly higher in the higher hemoglobin group (n=13, 65%) than the lower hemoglobin group (n=7, 7.6%) (p<0.001). Finally, the number of patients who received a diagnosis of PV was significantly higher in the higher hemoglobin group (n=13, 65%) than the lower hemoglobin group (n=9, 9.8%) (p<0.001). Conclusion: We found a substantial increase in patients who were candidates for testing for PV with the introduction of WHO 2016 criteria; these patients were diagnosed with PV with a rate (9.8%) that cannot be underestimated.

Chanarin-Dorfman syndrome.

Chanarin Dorfman syndrome is a multisystem, very rare, autosomal recessive lipid storage disorder, characterized by the accumulation of lipid vacuoles in neutrophils, and was first described by Dorfman in 1974. Due to a mutation in the ABHD5 gene of the short arm of chromosome 3, lipid is stored in the granulocytes at various sites in the human body, such as the muscle, liver, eye, ear, central nervous system, and bone marrow. Clinically, the disease is presented with ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation. A 38-year-old male patient was referred to our Internal Medicine Clinic for consultation with laboratory findings as follows: high aspartate aminotransferase (AST; 203 U/L), alanine aminotransferase (ALT; 151 U/L), gamma-glutamyl transferase (GGT; 167 U/L), creatine kinase (CK; 1127 U/L) levels and low platelet levels (108000). After ultrasonography and gastroscopy, the patient was diagnosed with liver cirrhosis. Bilateral mixed-type hearing loss on audial tests and bilateral punctuate keratopathy, ectropion, and cataract in the left eye on ophthalmological tests were found. For the definitive diagnosis of Chanarin Dorfman syndrome, peripheral blood was examined, which revealed lipid accumulation in the neutrophils (Jordan's anomaly). We emphasize that if a patient has unusual findings, such as ichthyosis, hearing loss, hepatomegaly, splenomegaly, cirrhosis, cataract, keratopathy, myopathy, and mental retardation, the possibility of Chanarin Dorfman syndrome should be considered.

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.

Could Neutrophil CD64 Expression Be Used as a Diagnostic Parameter of Bacteremia in Patients with Febrile Neutropenia?

OBJECTIVE: The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia. MATERIALS AND METHODS: All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France), identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux), and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP) was measured by turbidimetric methods (Biosystems, Spain) and erythrocyte sedimentation rate (ESR) was measured by the Wintrobe method. RESULTS: In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005). In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965)] predictive value (p=0.001). In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005). CONCLUSION: Neutrophil CD64 expression could be a good predictor as an immune parameter with high sensitivity and a negative predictive value for bacteremia in febrile neutropenic patients.

Novel antifungal drugs against fungal pathogens: do they provide promising results for treatment?

The febrile neutropenia episodes of hematological patients and their outcomes were evaluated with respect to fungal pathogens and antifungal therapy in this retrospective study. All patients, who were older than 14 years of age and developed at least one neutropenic episode after chemotherapy due to hematological cancer from November 2010 to November 2012, were included into the study. We retrospectively collected demographic, treatment, and survival data of 126 patients with neutropenia and their 282 febrile episodes. The mean Multinational Association for Supportive Care in Cancer score was 17.18 ± 8.27. Systemic antifungal drugs were initiated in 22 patients with 30 culture-proven invasive fungal infections (IFIs), 25 attacks of 19 patients with probable invasive pulmonary aspergillosis (IPA), 42 attacks of 38 patients with possible IPA, and 31 attacks of 30 patients with suspected IFI. Voriconazole (VOR), caspofungin and liposomal amphotericin B were used to treat 72 episodes of 65 patients, 45 episodes of 37 patients and 34 episodes of 32 patients as a first-line therapy, respectively. Unfavorable conditions of our hematology ward are thought to increase the number of cases with invasive pulmonary aspergillosis and VOR use. It should be taken into consideration that increased systemic and per oral VOR usage predisposes patients to colonization and infection with azole-resistant fungal strains. Catheters should be removed in cases where patients' conditions are convenient to remove it. Acute myeloblastic leukemia cases that are more likely to develop invasive fungal infections should be monitored closely for early diagnosis and timely initiation of antifungal drugs which directly correlates with survival rates.

Which Multidrug-Resitant Bacteria are Emerging in Patients with Hematological Malignancies?: One-Year Report.

The aim of this retrospective, observational study was to evaluate the outcomes of bacteremia attacks during neutropenic episodes caused by chemotherapy in patients with hematological cancers by assessing mortality, involved pathogens, antimicrobial therapy and treatment responses. Patients who were older than 14 years of age and developed at least one neutropenic episode after chemotherapy to treat hematological cancer between November 2011 and November 2012 were included in the study. We retrospectively collected demographic, treatment, and survival data for 68 patients with 129 neutropenic episodes. The mean age was 59.36 ± 15.22 years (range 17-80 years), and 41 cases were male. The mean Multinational Association of Supportive Care in Cancer score was 19.56 ± 9.04. A total of 37 (28 %) bacteremia attacks were recorded in 20 cases (29 %). Fatality rates were 50 % in the six cases with bacteremia caused by carbapenem-resistant Gram-negative bacteria; death occurred in two patients with carbapenem-resistant Acinetobacter baumannii and in one patient with carbapenem-resistant Pseudomonas aeruginosa. Clinical and microbiological responses were achieved using PIP-TAZ or CEP-SUL treatment in 80 % (16/20) of the cases with bacteremia caused by carbapenem-sensitive Gram-negative bacteria (CS-GNB). During 547 colonization-days in 21 (30 %) vancomycin-resistant enterococci (VRE)-colonized cases among 68 patients, vancomycin-resistant Enterococcus faecium bacteremia developed in two patients. Non-carbapenem-based therapy can cure most bacteremia attacks caused by CS-GNB in patients with hematological cancer. However, bacteremia and other infections caused by drug-resistant pathogens, such as A. baumannii, P. aeruginosa, and VRE, are a growing concern in hematological patients.

Bloodstream infections in patients with hematological malignancies: which is more fatal - cancer or resistant pathogens?

BACKGROUND: The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. METHODS: In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. RESULTS: During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. CONCLUSION: BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible or probable invasive fungal infections with an absence of pulmonary findings due to increase azole resistance.

Vancomycin-resistant enterococci colonization and bacteremia in patients with hematological malignancies.

INTRODUCTION: We retrospectively evaluated the rates of vancomycin-resistant enterococci (VRE) colonization and VRE-related infections in patients with hematological malignancies. METHODOLOGY: All patients in the hematology department of the Ministry of Health Okmeydani Training and Research Hospital, an 800-bed tertiary hospital in Istanbul, Turkey, older than 14 years of age and who developed febrile neutropenia during chemotherapy for hematological cancers between November 2010 and November 2012 were evaluated in this retrospective observational study. RESULTS: A total of 282 neutropenic episodes in 126 patients who met the inclusion criteria were analyzed. The mean patient age was 51.73 ± 14.4 years (range: 17-82 years), and 66 cases occurred in male patients. The mean Multinational Association for Supportive Care in Cancer score of patients with hematological malignancies was 17.18 ± 8.27. Fifty (39.68%) patients were colonized with VRE, and the mean number of VRE colonization days per patient was 34.27 ± 13.12 days. Only two patients developed VRE bacteremia: a male patient with non-Hodgkin's lymphoma who survived the infection, and a female patient with acute myeloid leukemia who died from VRE bacteremia. CONCLUSIONS: Patients with hematological malignancies accompanied by VRE colonization should be expected to develop VRE- or vancomycin-sensitive enterococci-related bacteremia under certain conditions, which include the development of severe mucositis, invasive procedures, and the use of intensive broad-spectrum antibiotics, even if infection control measures are implemented properly.

Primary or secondary antifungal prophylaxis in patients with hematological maligancies: efficacy and damage.

BACKGROUND: Patients with hematological malignancies often develop febrile neutropenia (FN) as a complication of cancer chemotherapy. Primary or secondary antifungal prophylaxis is recommended for patients with hematological malignancies to reduce the risk of invasive fungal infection (IFI). This study retrospectively evaluated the efficacy and potential harm of administration of primary and secondary antifungal prophylaxis to patients with hematological malignancies at one hospital. METHODS: All patients with hematological malignancies older than 14 years of age who had experienced at least one FN attack during chemotherapy while being treated at one hospital between November 2010 and November 2012 were retrospectively evaluated. RESULTS: A total of 282 FN episodes in 126 consecutive patients were examined during a 2-year study period. The mean patient age was 51.73±14.4 years (range: 17-82 years), and 66 patients were male. Primary prophylaxis with posaconazole was administered to 13 patients and systemic antifungal treatment under induction or consolidation chemotherapy to seven patients. Of 26 patients who received secondary antifungal prophylaxis with either oral voriconazole (n=17) or posaconazole (n=6) during 46 FN episodes, systemic antifungal therapy was administered in 16 of 38 episodes and three of eight episodes, respectively. Secondary antifungal prophylaxis with caspofungin was found effective in treating six FN episodes in three patients who had experienced at least two persistent candidemia attacks. The mortality rates associated with IFI were 9% in the first year, 2% in the second year, and 6% overall. The mortality rates associated with candidemia were 33% in the first year, 22% in the second year, and 27% overall. CONCLUSION: Primary antifungal prophylaxis should be administered to selected patients on the basis of consideration of efficacy, cost, and potential harm. Use of secondary prophylaxis may reduce systemic antifungal use and IFI frequency but may increase risk of colonization and infection with azole-resistant fungal strains.

Vancomycin-resistant enterococci colonization in patients with hematological malignancies: screening and its cost-effectiveness.

BACKGROUND AND OBJECTIVE: We evaluated the rates of vancomycin-resistant enterococci (VRE) colonization and VRE-related bacteremia in patients with hematological malignancies in terms of routine screening culture and its cost-effectiveness. MATERIALS AND METHODS: All patients of the hematology department who were older than 14 years of age and who developed at least one febrile neutropenia episode during chemotherapy for hematological cancers between November 2010 and November 2012 were evaluated retrospectively. RESULTS: We retrospectively analyzed 282 febrile episodes in 126 neutropenic patients during a two-year study period. The study included 65 cases in the first study-year and 78 cases in the second study-year. The numbers of colonization days and colonized patient were748 days of colonization in 29 patients (44%) in the first study-year and 547 colonization days in 21 patients (26%) in the second study-year, respectively. Routine screening culture for VRE cost $4516,4 (427 cultures) in the first study-year, $5082,7 (504 cultures) in the second study-year depending on the number of patients and their length of stay. CONCLUSION: In line with our study results, routine screening of hematological patients for VRE colonization is not costeffective. Routine surveillance culture for VRE should be considered with respect to the conditions of health care setting.