Determination of drug-related problems in the hematology service: a prospective interventional study.

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%). CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

East Mediterranean region sickle cell disease mortality trial: retrospective multicenter cohort analysis of 735 patients.

Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-ß(0) thalassemia (17 %), Hgb S-ß(+) thalassemia (15 %), and Hb S-α thalassemia (1 %). They were followed for a median of 66 ± 44 (3-148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18-54) years for males, 40.1 ± 15 (17-64) years for females, and 36.6 ± 13 (17-64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education.

Adipose tissue indices predict prognosis in hodgkin lymphoma.

INTRODUCTION BACKGROUND: This study evaluated the impact of adipose tissue indices on prognosis of HL. METHODS: Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival. RESULTS: For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant. CONCLUSION: SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.

Successful management of imatinib despite alopecia and nail necrosis.

Imatinib mesylate selectively inhibits bcr/abl and other non-specific tyrosine kinases, such as c-kit and platelet derived growth factor (PDGF) receptor and successfully used to treat chronic myeloid leukaemia (CML). In most cases, the drug is well tolerated: however, side effects can be seen. Hair loss and paronychia inflammation were often reported with Imatinib, but total alopecia was rarely mentioned. We report a CML patient who was presented with alopecia and paronychia inflammation probably induced by imatinib therapy. We have successfully treated our patient by cessation and then re-applying therapy with lower doses after improvement of lesions and have not found a similar report in literature.

Low plateletcrit is associated with reduced progression: Free and overall survival in chronic lymphocytic leukemia.

Background: Alterations of plateletcrit and mean platelet volume (MPV) and pathogenesis of chronic lymphocytic leukaemia (CLL) have been linked to various inflammatory disorders. The prognostic impact of plateletcrit and MPV were evaluated. Methods: MPV and plateletcrit levels of both CLL and control group were compared and then in CLL patients, additional diseases, leukocyte count, platelet count, lactate dehydrogenase, Rai stage, progression-free and overall survival, mutations, if any, and chemotherapy, if any, were recorded. Then, the relationship between MPV and plateletcrit values and these parameters were evaluated in CLL patients. Results: Platelet and plateletcrit values were found to be significantly lower in CLL patients than the control group (p<0.001) for both. Plateletcrit and MPV values of patients who did not receive chemotherapy were higher than those who received chemotherapy (p=0.03, p=0.02, respectively). Being over 75 years old, plateletcrit value less than 0.1565 %, platelet level below 175 x 109/L, and leukocyte count greater than 53.5 x 109/L was found to significantly reduce overall survival. Male gender, each stage increase, plateletcrit less than 0.1565 % and leukocyte count greater than 53.5 x 109/L was related to reduce treatment-free survival in CLL patients. Conclusions: Plateletcrit can be a viable prognostic marker for defining both treatment free and overall survival.

Malignancy-related mir-210, mir-373 and let-7 levels are affected in iron deficiency anemia.

Background: Hypoxia is the hallmark of iron deficiency anemia (IDA) and in hypoxic environment, significant changes are observed in malignancy-related microRNAs (miRNA). Our aim is to examine whether there is any difference in the levels of miR-210, miR-373 and let-7, which are directly related to malignancies in patients with IDA. Methods: Thirty-five female patients with IDA between the ages of 18-65 and 10 healthy controls were included in the study. Patients who received oral iron therapy, who had inflammatory disease, and who were pregnant were excluded from the study. Student t Test was used for comparing variables with normal distribution in two independent groups, and Mann-Whitney U Test was used for variables without normal distribution. Comparison of categorical data was made using the chi-square test. Results: The mean hemoglobin and ferritin level were 10,78±0,93 and 6.28±5,76 respectively. Plasma miR-210 expression were found as -7.27±2.23 and -6.15±0,88 in IDA and control group respectively (p = 0.022). Plasma miRNA-373 were -7.36±2,58 and -6,96±1,93 and let-7 expression were 2.14±2,15 and 3,57±2,21 in IDA and control group. (p = 0.65 and p = 0.20, respectively). Conclusions: Plasma miR-210 expression was significantly up-regulated and miR-373 and let-7 expression was down-regulated, though insignificantly, in IDA group.

A tale of two diseases: Sarcoidosis, COVID-19 and new therapeutic options with dual RAS inhibition and tetanus-diphtheria vaccine.

Sars Cov-2, the pathogen which belongs to the beta coronavirus family that is responsible for COVID-19, uses Angiotensin Converting Enzyme 2 (ACE2) as a receptor, which is responsible for controlling the actions of renin-angiotensin system (RAS). Sars Cov-2 - ACE2 binding leads to a RAS mediated immune response, which targets especially lungs to form ARDS, which in turn, is the most important cause of mortality in COVID-19. CD8+ T cell response dominates over CD4+ T cell response and natural killer cell dysfunction also leads to CD4+ cell dysfunction in COVID-19; this immune dysregulation leads to inappropriate (ARDS) and inadequate (low or quickly waning antibodies) responses to the disease and unfortunately, prepares the patients for re-infections. The peripheral anergy seen in chronic sarcoidosis has much resemblance to COVID-19; CD8+ T cell accumulation is also responsible for inadequate reaction to tuberculin and antigenic stimulus. This article, based on the similarity of COVID-19 and sarcoidosis, discusses a combination of the therapeutic strategy of the tetanus-diphtheria vaccine and dual RAS inhibition, alongside with hydroxychloroquine and antiviral agents, as a solution to overcome the problems described above.

Aplastic anemia, mucormycosis and aspergillosis in infectious mononucleosis: success is possible.

Infectious mononucleosis (IM) is a rare cause of aplastic anemia in adults. We report of a patient in whom aplastic anemia, mucormycosis and aspergillosis complicated during the course of IM and successfully treated with liposomal amphotericin B. According to our searches in literature, we could not find a similar patient complicated and successfully treated like ours.

Peripheral FLT-3 ligand levels as a pathobiological parameter duringthe clinical course of acute myeloid leukemia.

BACKGROUND/AIM: FLT-3 ligand is a growth factor affecting the hematopoietic lineage. The aim of this study was to evaluate the variability of peripheral FLT-3 ligand during the clinical course of acute myeloid leukemia (AML) patients. MATERIALS AND METHODS: Twenty-four patients were enrolled in this study in order to assess alterations in the circulating levels of FLT-3 ligand during the clinical course of AML. RESULTS: We studied the association in the diagnostic period between the FLT-3 ligand and peripheral blood cells together with serum electrolytes. FLT-3 ligand levels (pg/mL) during the aplastic period due to remission induction and consolidation were higher than the levels at initial diagnosis. On the other hand, the diagnostic and remission induction values of leukocytes and FLT-3 ligand showed an inverse association. These results indicate to us that higher white cell counts are associated with lower FLT-3 ligand levels. We also found a reversed association between FLT-3 ligand and serum lactate dehydrogenase level. However, there was no association between FLT-3 ligand and other serum electrolyte levels. We also found higher FLT-3 ligand levels in male patients. CONCLUSION: Our study demonstrates the inverse proliferative action of FLT-3 ligand on the early myeloid lineage. In addition, this study showed us that FLT-3 receptor inhibition during chemotherapy-induced aplasia causes a compensative ligand overexpression.

Disseminated Aspergillosis due to Aspergillus niger in Immunocompetent Patient: A Case Report.

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Many cases of pulmonary, cutaneous, cerebral, and paranasal sinus aspergillosis in immunocompetent patient were defined in literature but disseminated aspergillosis is very rare. Here we present an immunocompetent case with extrapulmonary disseminated aspergillosis due to Aspergillus niger, totally recovered after effective antifungal treatment with voriconazole.

Aberrations of chromosomes 9 and 22 in acute lymphoblastic leukemia cases detected by ES-fluorescence in situ hybridization.

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.

Brucellosis: a rare cause of febrile neutropenia in acute myeloblastic leukemia.

Brucellosis is a zoonotic disease and endemically seen in the Middle East, Eastern Europe and continental America. Febrile neutropenia related to Brucellosis has been reported only in a few cases. Brucella was cultured from the bone marrow of a 42-year-old woman who was admitted to hospital with symptoms of fever and fatigue and later diagnosed as acute myeloblastic leukemia (AML). The patient was treated for both AML and Brucellosis without any problems and discharged from the hospital after scheduling her follow-up visits. Brucellosis might be considered in the etiology of febrile neutropenia in endemic regions and must be treated effectively to prevent possible morbidity and mortality during or after chemotherapy.