Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. PATIENTS AND METHODS: The study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. RESULTS: A total of 141 healthy donors with a median donor age of 32 (18-64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/µL in the adequate mobilization group and 46/µL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/µL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90-0.99), p < 0.001]. CONCLUSION: The result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

Evaluation of oral manifestations and head and neck lymphadenopathy in newly diagnosed acute leukemia patients.

OBJECTIVES: To determine the frequency of head and neck lymphadenopathy (LAP) and intraoral findings (non-dental/dental) in patients with newly diagnosed acute leukemia (AL). SUBJECTS AND METHODS: Twenty-eight (52.8%) females and 25 (47.2%) males in a total of 53 patients with newly diagnosed AL with a mean age of 46 years were included in the study. Personal information, the type of AL (AML [acute myelogenous leukemia]/ALL [acute lymphocytic leukemia]), and hematological findings (anemia, neutropenia, and thrombocytopenia) were obtained from medical records. One of two calibrated oral diagnosis and maxillofacial radiology specialists performed extraoral (head and neck LAPs) and intraoral (non-dental and dental) clinical examinations. The Chi-square (χ2 ) test was used to evaluate categorical variables. RESULTS: LAP was observed in 22.6% and intraoral findings in 30.2% of the patients. LAP was most commonly observed in the neck and none in the parotid glands. The most intraoral findings were gingival/mucosal bleeding and oral petechiae/ecchymosis. While there was no statistical difference between AML and ALL patients in terms of LAP (p > .05), intraoral findings were observed more in patients with AML (p < .05). Only two (3.8%) patients had dental findings. With a slight difference, intraoral findings were more with thrombocytopenia and LAP with neutropenia. CONCLUSION: In AL, especially non-dental intraoral findings are common. The fact that dentists working in the oral cavity are often the first specialists to encounter the oral manifestations of AL imposes an important role in early diagnosis and treatment.

An effective treatment in Erdheim Chester disease: vemurafenib: a case report.

BACKGROUND: Erdheim Chester disease (ECD) is a rare disease with multisystemic involvement in the group of non-langerhans cell histiocytosis. Although nearly 100 years have passed since its definition, the number of cases reported all over the world is below 1000. In addition to the rarity of the disease, low awareness seems to play a role in this. CASE PRESENTATION: 47-year-old white caucasian women patient who presented to our clinic with symptoms of weakness-fatigue as well as increasing pain in the knees and ptosis in the left eye. Result of the patient's bone biopsy, ECD was considered pathologically and BRAF V600E mutation was shown molecularly. After presenting the clinical, laboratory and other examination results of the case, the dramatic response seen with targeted therapy will be discussed. CONCLUSIONS: BRAF V600E mutation is frequently seen in ECD. Vemurafenib plays an active role in targeted therapy.

Single-Dose Rasburicase Might Be Adequate To Overcome Tumor Lysis Syndrome In Hematological Malignancies.

INTRODUCTION: Tumor lysis syndrome (TLS) is a commonly observed oncological emergency that requires prompt diagnosis and treatment. Rasburicase is a recombinant urate oxidase endorsed in TLS for the treatment of hyperuricemia. The effect of single-dose 7.5 mg rasburicase at longer follow-ups was not widely investigated. PATIENTS AND METHODS: Eighty-two patients included in the study with clinical TLS and laboratory TLS. The primary endpoint was the normalization of uric acid (<6mg/dL) within 24 hours of rasburicase administration, which was described as treatment success. The secondary endpoint was defined as having sustained response at the first week. The third endpoint was defined as the reaching the baseline renal function before TLS. RESULTS: We found that the use of a 7.5 mg dose of rasburicase controlled uric acid in 74 of 82 (90,2%) patients at the 24th hour. In the first week, uric acid remained at normal levels in 69 of 82 (84,1%) patients. At 24 hours, the TLS risk group was the only predictor for failing uric acid normalization; at the end of the first week, no predictive factor was identified for failing uric acid normalization. CONCLUSION: Rasburicase at 7.5 mg dose is an important agent for controlling laboratory and clinical TLS at 24 hours and extending its effect to the first week.

Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) has an increasing incidence in elderly patients with poorer prognosis than in younger patients. Clinicians should clearly identify the characteristics and prognostic factors of elderly patients. We analyzed the outcome of elderly DLBCL patients, especially factors affecting survival in real-life clinical practice. MATERIALS AND METHODS: The data of 330 DLBCL patients at our center were retrospectively evaluated by dividing three groups; younger than 65 years, between 65-79 years, and 80 years and older. We examined the factors affecting survival in DLBCL patients ≥ 65 years old. RESULTS: The median age of the patients was 61 years (range 16-87). 192 (58.2 %) of our patients were younger than 65 years old, 112 (33.9 %) were between 65-79 years, and 26 (7.9 %) patients were 80 years old or older. The median follow-up was 15 (1-120) months. Median PFS was 38 months in the 65-79 years group, ten months in the ≥ 80 years group; meanwhile, median OS was 43 months in the 65-79 years group, 25 months in the ≥80 years group. The number of patients who relapsed within 12 months of the first-line treatment was 69 (35.9 %) in the <65 years group, it was 60 (53.6 %) in 65-79 years group, and 22 (84.6 %) in ≥80 years group (p < 0.001). The median OS was 9 (7.1-10.9) months in DLBCL patients older than 65 years old who relapsed within 12 months. Early relapse, failure to achieve CR after first-line chemotherapy, and high IPI score were associated with poor survival in patients ≥ 65 years old (p:0.001). CONCLUSION: Advancing age was a poor prognostic factor for survival of DLBCL. Relapsing within the first year, or failure to achieve complete remission were associated with poorer survival of the elderly DLBCL patients. R-CHOP is the standard treatment in DLBCL, and the best responses are obtained regardless of age. Due to difficulty in receiving standard treatments, novel treatment modalities are needed for better outcomes in elderly patients with DLBCL.

Does myeloma genetic have an effect on stem cell mobilization?

BACKGROUND: Autologous stem cell transplantation (ASCT) after induction treatment is the standard of care. Our understanding of myeloma genetics has been very limited and its effect to stem cell mobilization is not widely investigated. We aimed to investigate the effect of genetic abnormalities on stem cell mobilization in myeloma. METHODS: The data of 150 MM patients who underwent stem cell mobilization at our center between 2009-2020 were included and analyzed retrospectively. Pre-treatment bone marrow cytogenetics and fluorescence in situ hybridization tests were performed for each patient. RESULTS: Groups were divided into two as patients with normal cytogenetic and abnormal cytogenetic. No difference observed between groups regarding age, gender and ECOG (p = 0.4; p = 0.2; p = 0.3). Groups were similar concerning myeloma characteristics, received treatment and treatment response. Median CD34+ cells/kg harvested was 444(2-11.29) in normal cytogenetic group whereas it was 4,8(2.4-8.6) in abnormal cytogenetic group(p = 0.2). Optimal CD34+ cells level achievement was 73 (67 %) in normal cytogenetic group while it was 25(71.4 %) in abnormal cytogenetic group(p = 0.6). Neutrophil and platelet engraftment durations were similar among cytogenetic groups (p = 0.7; p = 0.9). R-ISS based groups were also did not differ regarding harvested CD34+ cells and achievement optimal CD34 level (p = 0.79, p = 0.74). Engraftment durations for neutrophil and platelet were comparable between R-ISS based groups (p = 0.59, p = 0.65) CONCLUSIONS: Here we were not able to find any impact of genetic abnormalities on stem cell mobilization in myeloma patients. Expanded studies can aid to identify the effect of particular genetic anomalies on the stem cell mobilization.

The effect of bulky mass on prognosis in diffuse large-B-cell lymphoma: still poor?

The introduction of rituximab to the CHOP protocol has demonstrated an improvement in PFS and OS in DLBCL patients with both early and advanced stages. Most studies in the pre-rituximab period indicated that bulky disease has an unfavorable impact on clinical outcomes of DLBCL. The effect of bulky mass on the outcome of DLBCL patients undergoing R-CHOP therapy remained uncertain. One-hundred-twelve newly diagnosed DLBCL patients aged 18 and older were enrolled in the study. Patients were divided into groups-based presence of bulky disease. 56 patients with bulky disease and their age, gender, ECOG score, Ann Arbor stage, immunohistochemical origin, treatment, radiotherapy and comorbidity 1:1 matched 56 control patients with non-bulky disease included. Overall response rate at end of treatment was similar among groups (p = 0.1). Patients with bulky disease and non-bulky disease were comparable regarding overall survival (p = 0,9). All cohort investigated for predictors for survival, after multivariate analysis, ECOG score, Ann arbor stage, IPI score and LDH level were found significant. Here, we found no impact of bulky disease on remission and survival. We believe, with increasing available data, poor prognostic value of bulky disease will be weakening in the rituximab era.

Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes.

INTRODUCTION: Allogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors' age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. METHOD: Sixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009-2019 were enrolled for the study. All donors received 4-5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50-54 group A, 55-59 group B, aged 60 and older group C. RESULTS: Pre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). CONCLUSION: Adequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.

Awareness, treatment rates, and compliance to treatment in patients with serum LDL cholesterol higher than 250 mg/dL, and possible, probable, or definite familial hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) is a genetic disease characterized by increased levels of low-density lipoprotein cholesterol (LDL-C). It is underdiagnosed and undertreated despite relatively high prevalance and significant association with increased mortality. We aimed to determine treatment status and compliance in patients with LDL-C ≥ 250 mg/dL and FH. DESIGN: Patients older than 18 years old and have a serum LDL-C ≥ 250 mg/dL between January 2010 to December 2016 were identified from the hospital database. A phone survey was performed. Demographic features, smoking status, alcohol use, exercise, cardiovascular disease (CVD), use of medication for dyslipidemia, and CVD and high cholesterol levels in the family were questioned. Dutch Lipid Clinical Network Criteria was used to classify patients. The study was registered to Clinicaltrials.gov in July 2020 (NCT04494464). RESULTS: 1365 patients with a LDL-C ≥ 250 mg/dL were identified. Patients that could not be reached and who refused to interview were excluded and the data of 367 patients were analyzed. There were 248 (67.6%) female and 119 (32.4%) male patients and mean age was 50.52 ± 11.66. LDL-C was ≥330 mg/dL in 50 (13.6%) and 250-329 mg/dL in 317 (86.4%) patients. Forty (10.9%) patients were classified as definite, 181 (49.3%) as probable and 146 (39.8%) as possible FH. 213 (58.0%) patients were not receiving lipid-lowering treatment, and 162 (76.1%) stated that medication was never recommended previously, 30 (14.1%) had stopped medication him/herself and 21 (9.8%) had stopped medication with the advice of the physician. Among patients with definite/probable FH, 84 (38.0%) had CVD and the rate of lipid-lowering drug use in these patients was 58.3%. CONCLUSION: A significant proportion of patients with LDL-C ≥ 250 mg/dL were not taking lipid-lowering drugs. Similar with many other studies, diagnosis, and treatment rates of FH patients were very low in our study. Further national studies are required to increase awareness of the disease in both physicians and patients.

Different pharmaceutical preparations of colchicine for Familial Mediterranean Fever: are they the same?

This study aimed to investigate the benefit of changing the pharmaceutical preparation of colchicine in Turkish Familial Mediterranean Fever (FMF) patients resistant to one preparation in terms of frequency of the attacks. Turkish adult FMF patients under treatment with an imported colchicine preparation-in the form of compressed tablet form-due to resistance to domestic colchicine preparations, which are film- or sugar-coated tablets, and not using anti-interleukin-1 or other biologic agents were included in the study. Baseline disease characteristics along with MEFV mutations were identified. Daily colchicine doses and attack frequencies before and after the pharmaceutical change were compared. Fifty patients resistant to coated tablet preparations of colchicine and under treatment with the compressed tablets were identified. The median duration of disease was 6 (interquartile range 2.7-14) years and duration under treatment with the imported colchicine was 21 (range 8-60) months. Eight (16%), ten (20%), and 32 (64%) patients had 0-3, 4-6, and more than 7 attacks per year, respectively, before the compressed tablets. After treatment with the compressed tablet form of colchicine, 44 (88%), 5 (10%), and 1 (2%) patients had 0-3, 4-6, and more than 7 attacks, respectively (p < 0.0001). Daily colchicine doses were similar before and after the pharmaceutical change (1.85 ± 0.47 vs 1.84 ± 0.37 mg, p = 0.9). Turkish FMF patients with ongoing attacks under domestic coated tablet preparations of colchicine may benefit from the compressed colchicine tablets. This may be explained by the difference in pharmacokinetic properties of different colchicine preparations.

The relationship between all-cause mortality sarcopenia and sarcopenic obesity among hospitalized older people.

BACKGROUND AND AIM: Sarcopenia and sarcopenic obesity (SO) are associated with adverse health outcomes in older people. Data on sarcopenia- and SO-related mortality are insufficient for hospitalized older people. The aim of this study was to evaluate the relationship between sarcopenia, SO and mortality among hospitalized older people. METHODS: Two-centered prospective observational study was conducted among 350 hospitalized older people in geriatric units of two university hospitals. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People. Obesity was defined according to fat mass percentage. Medical history, cognitive status, nutritional status and functionality and laboratory tests were assessed. All-cause mortality rate was recorded at 2 years. RESULTS: The prevalence of SO was 21.1%. The prevalence of sarcopenia was 11.4%. Both sarcopenia (log rank p < 0.001) and SO (log rank p < 0.001) were associated with all-cause mortality at 2 years. There was no difference between sarcopenia and SO for mortality. SO (HR 5.23, p < 0.001), sarcopenia (HR 9.26, p < 0.001), male gender (HR 2.25, p = 0.035), Lawton IADL (HR 0.77, p = 0.02), heart failure (HR 3.25, p = 0.02) and chronic obstructive lung disease (HR 5.16, p = 0.01) were independently related to all-cause mortality. DISCUSSION AND CONCLUSIONS: Both sarcopenia and SO showed an independent relationship for 2-year all-cause mortality after hospital discharge. These results suggest that preventive and treatment options should be taken to decrease mortality associated with these conditions among hospitalized older people.

Prognostic effect of red cell distribution width-to-platelet ratio in colorectal cancer according to tumor stage and localization.

INTRODUCTION: Colorectal cancer (CRC) is one of the most common cancers worldwide and survival is still approximately 24 months. Recently, importance of the molecular features, tumor localization, and also inflammatory status is increased, and most of these entities can be used as a predictive marker for colon tumor. However, since most of these tests are expensive and unachievable, there is a need for new prognostic and predictive markers that can be used easily and are inexpensive. AIM: We aimed to investigate the prognostic effect of red cell distribution width (RDW)-to-platelet ratio (RPR) which reflects inflammatory status and can be calculated basically by using center blood count (CBC) parameters on CRC according to tumor stage and localization. METHODS: Newly diagnosed 312 CRC patients between 2010 and 2016 were retrospectively analyzed. Patients' demographics, including survival data and tumor characteristics, were obtained from medical charts. RPR was calculated using CBC parameters at the time of diagnosis. Cutoff value for RPR was set at 0.05 and the patient population was divided into two arms (arm A: RPR ≥0.05 and arm B: RPR <0.05). The patients were stratified according to the tumor stage (early and advanced disease) and tumor localization (right sided and left sided). RESULTS: Totally, 312 patients were enrolled to the study. Nearly 81.9% of the patients were at early stage and 18.1% were at advanced stage at the time of diagnosis. In patients with early-stage disease, no significant disease-free survival and overall survival (OS) was found in both arms (P = 0.88 and P = 0.085, respectively). In arm A, OS was nonsignificantly better in the entire and left-sided advanced tumor compared to arm B. In patients with right-sided advanced cancer, OS was statistically significantly better for arm A compared to arm B (median OS; RPR ≥0.05: 24.8 months vs. <0.05: 13.9 months; P = 0.035). DISCUSSION: RPR can be a useful prognostic marker in CRC, especially in right-sided advanced tumors. CONCLUSION: RPR can be used as a prognostic marker in CRC but should be validated with further investigation.