Hematologic Dyscrasias Research Articles

Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18–30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5–10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

Epidemiological Insights into Large Granular Lymphocyte Leukemia: A Nationwide SEER Database Study

Background: Large granular lymphocytic (LGL) leukemia is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T-LGL) or natural killer (NK) cells. LGL leukemia accounts for 2% to 5% of chronic lymphoproliferative disorders in the United States of America. LGL leukemia can either present as an indolent type or an aggressive type. Most patients remain asymptomatic and often have associated autoimmune diseases, such as rheumatoid arthritis and hematologic dyscrasias. We analyzed the demographic characteristics of LGL leukemia patients and investigated the influence of social determinants on their survival. Methods: We performed a retrospective cohort study of the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with LGL leukemia between years 2000 and 2020. Patient demographics, year of diagnosis, and timeline of treatment were analyzed by descriptive statistics. Cox proportional hazards regression analysis was performed to identify the factors influencing the survival of these patients. Results: A total of 2589 patients were diagnosed with LGL leukemia. Median age of diagnosis was 67 years. 59.4% were aged more than 65 years of age at the time of diagnosis, 52.7% were males, 81.5% were Caucasians, 64% had an annual income of more than $65,000, and 84.2% lived in metropolitan areas. 91.8% were diagnosed in the past decade after 2010. It is worth noting that 64.5% of the patients received treatment more than six months after diagnosis of LGL leukemia. 81.5% of patients were Caucasians, 9.6% were African Americans, 5.3% were Asians/Pacific Islanders, followed by 2% Hispanics and 1.5% American Indians. At the time of the last follow-up, 65.5% of patients were alive, with an overall median survival of forty months. 70% of patients had LGL leukemia as the only primary malignancy. Age less than 65 years had better outcomes than the older age group (HR 0.32). Female gender was protective (HR 0.69). Poor outcomes were seen in patients with an annual income of less than $65,000 (HR 1.21). The year of diagnosis and residence had no significant effect on survival. Marriage improved the outcomes of patients (HR 0.78) (Table 1). Patients receiving treatment within six months of diagnosis had higher mortality (HR 1.43) than the rest of the population. Caucasians comprised majority of the patient population and had better prognoses (HR 0.11) than Asians/Pacific Islanders (HR 0.49), Hispanics (HR 0.82), and African Americans (HR 0.97) (Figure 1). Conclusion: We present a population-based analysis and the determinants of survival in patients with LGL leukemia, a rare malignancy. The number of cases has increased in the past decade. Significant patient factors influencing survival in LGL leukemia patients include younger age at diagnosis, female gender, marriage and higher annual income.

Sweet’s Syndrome: A Rare Case Report

Sweet’s Syndrome, also known as acute febrile neutrophilic dermatosis is a rare disease of unknown etiology, but has been associated with autoimmune processes, malignancies, infections, GI disorders and drug reactions. It is more prevalent in women than men, except in case of malignancy associated origin. Clinical features of this disorder include acute onset of painful plaques on skin, neutrophilic leukocytosis, fever, dermal infiltrations by neutrophils. Usually, sweet’s syndrome is presented in three main clinical settings which includes: the classical (idiopathic), malignancy-associated, and drug induced. Classical Sweet’s Syndrome (CSS) is usually seen in women between the age of 30 to 50 years. It is frequently preceded by an upper respiratory illness and could be linked to pregnancy, inflammatory bowel disease, and both. Recurrence of the dermatosis is usually seen in one third of the patients experiencing classical sweet’s syndrome. Malignancy associated Sweet’s Syndrome (MASS) is usually present in patients with confirmed cancer and manifested as a paraneoplastic syndrome. Also occurs in those whose solid tumor or hematologic dyscrasia associated with sweet’s syndrome was previously undetected. Drug induced Sweet’s Syndrome (DISS) occurs in patients being treated with granulocyte-colony stimulating factor. Various other drugs including antibiotics like Minocycline, Trimethoprim Sulfamethoxazole, nitrofurantoin, antiepileptics like Carbamazepine, Diazepam, NSAIDS, Diuretics and Retinoids can also cause DISS. Diagnosis of sweet syndrome is usually done by two major criteria (histopathology and acute cutaneous lesion), and four minor criteria’s (infection, malignancy, medications, fever, and extra cutaneous manifestations like leukocytosis and corticosteroid response. Systemic corticosteroids are the golden standard of treatment for Sweet’s Syndrome. Systemic corticosteroids (0.5mg to 1mg/kg/day) for 4-6 weeks improves the systemic symptoms and reduce the skin lesions. For treating localized lesions, topical application of high potency corticosteroids or intralesional corticosteroids are effective. Other first line agents including potassium iodide and colchicine are also used. Second line agents include Indomethacin, Cyclosporine, Dapsone and Clofazimine. Keywords: Sweet’s Syndrome, Corticosteroids, Malignancy, Leukocytosis

#5430 ANTI-PLA2R ASSOCIATED MEMBRANOUS NEPHROPATHY AND CHRONIC LYMPHOCYTIC LEUKAEMIA, IS THERE A LINK?

Abstract Background and Aims The spectrum of glomerular lesion that occurs in the context of plasma cell dyscrasias (PCD) is wide, including type I and type II membranoproliferative glomerulonephritis (MPGN), focal proliferative GN, membranous nephropathy (MN), minimal change disease and amyloidosis. A clear-cut link between hematological dyscrasias and glomerulopathy is often offered by the finding of paraproteins in the kidney or by kidney leucocytic infiltration and, in these scenarios, malignancy treatment is often found to be also effective towards the glomerulopathy. In the context of PCD in which proliferation of the B-cell clone does not lead to plasma-cell terminal differentiation such as chronic lymphocytic leukemia (LLC) the physiopathological link with glomerulonephritis is not well established and it's hard to determine whether the combination of these two disorders is fortuitous. With regarding to MN, it's now well established that this histopathological pattern must be related to the presence of circulating autoantibodies, where anti-PLA2R auto-antibodies usually been associated with primary MN. To our knowledge association between LLC and anti-PLA2R associated MN has not been described. Case report We report the case of a 76-year-old man who was admitted in February 2022 with anasarca and acute kidney injury. He had recently been evaluated by a hematologist in the context of suspected chronic lymphocytic leukemia (CLL). Laboratory findings, along with typical CLL white blood cell count, showed decreased kidney function from baseline and were compatible with nephrotic syndrome, with proteinuria progressively increasing up to 27 gr/24 h in the following weeks. CLL was confirmed by lymphocyte typing. A total body CT scan showed mediastinal, abdominal and inguinal lymphadenopathies, but no suspected neoplastic lesions. Screening for autoimmunity tested completely negative, as well as infectious screening for common hepatic viruses (HBV, HAV, HCV), EBV, CMV, HIV, Parvovirus B19. Lymph node biopsy showed no aspects of aggressive lymphoproliferative disease and hematological consultation only indicated clinical and laboratory follow-up of LLC, with no further indication to specific therapies. A kidney biopsy was performed showing diffuse thickening of the basement membrane (Fig. 1) with granular deposition of IgG (+++) and C3 (++) along the glomerular capillary walls at immunofluorescence. Electron microscopy revealed subepithelial immune deposits (Fig. 2) with initial incorporation from the glomerular basement membrane (GBM). Anti PLA2R antibodies, found negative at first determination, subsequently tested positive at high titre (ELISA 1356.4 U/ml). A diagnosis of stage two membranous nephropathy was made, and the patient was treated with Rituximab 375 mg/m2 every week for four weeks. Clinical stability was obtained with repeated intravenous administration of diuretics (furosemide 60 mg + canrenone 200 mg) along with albumin. Nevertheless, nephrotic syndrome persisted, and kidney function progressively decreased with serum creatinine up to 2.8 mg/dL. Immunophenotype, which showed reduction but no suppression of CD19+ lymphocytes, was again repeated on November 2022 and showed typical LLC findings (CD 19+, CD 20+, CD 23+, CD 5+) with repopulation of CD19+ lymphocytes. Anti PLA2R antibodies gradually decreased instead, reaching a value of ELISA 1.8 U/ml in November 2022 and persisted negative until present. The patient recovered from nephrotic syndrome in Autumn 2022 and is currently on stage G3B chronic kidney disease with persistent sub-nephrotic proteinuria in supportive treatment. Conclusion Simultaneous diagnosis of primary MN and LLC led us to ask ourselves whether this patient could benefit from LLC-specific chemotherapy, even though there were no signs of aggressive hematological disease and no clear link with the nephropathy. We think that further investigations are required to deeply understand the connection between hematological and renal disorders, in order to identify whether there are two diseases to treat separately or two sides of the same disease to treat as one.

Localized Cutaneous Nodular Amyloidosis: A Specific Cutaneous Manifestation of Sjögren's Syndrome.

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition attributed to plasma cell proliferation and the deposition of immunoglobulin light chains in the skin without association with systemic amyloidosis or hematological dyscrasias. It is not uncommon for patients diagnosed with PLCNA to also suffer from other auto-immune connective tissue diseases, with Sjögren's syndrome (SjS) showing the strongest association. This article provides a literature review and descriptive analysis to better understand the unique relationship between these two entities. To date, 34 patients with PLCNA and SjS have been reported in a total of 26 articles. The co-existence of PLCNA and SjS has been reported, especially in female patients in their seventh decade of life with nodular lesions on the trunk and/or lower extremities. Acral and facial localization, which is a typical localization of PLCNA in the absence of SjS, seems to be much more unusual in patients with associated SjS.

Haematological and hepatic adverse effects of ceftriaxone in ambulatory care: a dual-centre retrospective observational analysis of standard vs high dose

BackgroundEuropean Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients.MethodAdult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher’s exact test used to identify statistical significance.ResultsIncidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26–2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87–2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36–10.92), p 0.655).ConclusionsIncreased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable—monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.

Efficacy of intra-articular injection of allogeneic platelet-rich plasma for knee osteoarthritis combined with hematologic blood dyscrasias with platelet dysfunction: protocol of a randomized, double-blind, placebo-controlled trial

BackgroundAutologous platelet-rich plasma (PRP) has been shown to alleviate the symptoms of patients suffering from knee osteoarthritis (KOA), but for certain patients with hematologic diseases with platelet dysfunction and patients receiving anti-platelet medications, autologous PRP is not an optimum solution. Allogeneic PRP has been proven to be safe and effective in the treatment of osteoarthritis, rotator cuff disease, refractory wounds and other medical fields. However, a well-designed and long-term follow-up prospective randomized controlled trial (RCT) to evaluate the effect of allogeneic PRP intra-articular injections for KOA combined with hematologic blood dyscrasias has not yet been performed.Methods/ designWe will conduct an allogeneic PRP injection for KOA combined with hematologic blood dyscrasias with platelet dysfunction study: a prospective, randomized, double-blind, placebo-controlled trial. One hundred participants with KOA combined with hematologic blood dyscrasias with platelet dysfunction will be randomly allocated to receive either one allogeneic PRP injection or one saline injection into the knee joint. The primary outcome will be a 12-month change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes will be the 36-Item Short-Form General Health Survey (SF-36) score, Lysholm score, overall knee pain score and MRI assessment at 1-, 3-, 6- and 12-month.DiscussionThe results of this study will help determine whether allogeneic PRP could be used as a non-surgical intervention to treat patients with knee OA combined with hematologic blood dyscrasias with platelet dysfunction.Trial registrationChinese Clinical Trials Registry reference: ChiCTR2100048624. Prospectively registered 11th of July 2021.

STUDY OF OPHTHALMIC MANIFESTATIONS IN PATIENTS WITH HAEMATOLOGICAL DYSCRASIAS

STUDY OF OPHTHALMIC MANIFESTATIONS IN PATIENTS WITH HAEMATOLOGICAL DYSCRASIAS

STUDY OF OPHTHALMIC MANIFESTATIONS IN PATIENTS WITH HAEMATOLOGICAL DYSCRASIAS

BackgroundAndObjectives:Haematologicaldyscrasiasreferstodisorders of the cellular elements of the blood, indicating a pathologicalcondition.Tostudythetypesofophthalmicmanifestationsinhaematological dyscrasias. Methods: This was a Descriptive cross-sectional study of 200cases admitted and diagnosed with various haematological dyscrasias inMedicine, Paediatrics wardsof the hospital betweenDecember 2020 toNovember2022.Allpatientsunderwentastandardisedandcomprehensiveophthalmic evaluation. Results:Outof200cases,152caseswereofnonmalignantdiseases,and 48 cases were of malignant diseases.Male cases were predominantly higherthan female cases. Conjunctival pallor was the most common anteriorsegment manifestation observed, and Retinal haemorrhage was the mostcommon posterior segmentmanifestation observedduring the studyperiod. Conclusion: It is essential to examine all patients with haematologicaldisordersforocularmanifestationsasithelpsindiagnosisandprognosis. Early recognition of the ocular manifestations is of greatimportance as an early treatment institution may prevent or alleviatebothocularandsystemic complications.

Neutropenia and Leukopenia After Cross Taper From Quetiapine to Divalproex for the Treatment of Borderline Personality Disorder.

Valproic acid (VPA) and its derivative, divalproex (DVP) can cause various hematologic dyscrasias, the most common being thrombocytopenia. Neutropenia and leukopenia have been reported in isolated cases, most occurring in pediatric patients or patients with epilepsy. We report a case of leukopenia and neutropenia that presented after cross taper from quetiapine to DVP for the treatment of borderline personality disorder. A 34-year-old male patient with history of posttraumatic stress disorder, opioid use disorder, alcohol use disorder, stimulant use disorder, cannabis use, and borderline personality disorder underwent a cross taper from quetiapine to divalproex (DVP). DVP was titrated to 1000 mg per day, complete blood count (CBC) was obtained after completion of cross taper and revealed neutropenia and leukopenia with no documented history of blood dyscrasias. Nine days after discontinuation of DVP, neutrophil and white blood cell count returned to normal limits. With a score of 7 on the Naranjo Adverse Drug Reaction Probability Scale, an adverse reaction of probable DVP-induced neutropenia was documented and medication was not resumed. This case suggests that there may be a correlation between DVP and isolated neutropenia and leukopenia. Although a CBC is collected routinely to monitor for thrombocytopenia, health care practitioners also should consider other blood dyscrasias. Further studies are warranted to determine incidence of neutropenia and leukopenia with DVP therapy and evaluate whether the medication can be safely continued in cases of mild-to-moderate neutropenia with close monitoring.

Interleukin-6 at the Host-Tumor Interface: STAT3 in Biomolecular Condensates in Cancer Cells.

It was recognized over 30 years ago that the polyfunctional cytokine interleukin-6 (IL-6) was an almost invariant presence at the host-tumor interface. The IL-6 in the tumor microenvironment was produced either by the cancer cell or by host stromal cells, or by tumor-infiltrating immune cells, or all of them. IL-6 effects in this context included local changes in tumor cell-cell and cell-substrate adhesion, enhanced motility, epithelial to mesenchymal transformation (EMT), and changes in cell proliferation rates in both solid tumors as well as hematologic dyscrasias. Locally produced IL-6 enhanced cancer-targeting functions of tumor-infiltrating macrophages and immune cells. Additionally, the sex-biased phenotype of certain cancers [e.g., hepatocellular carcinoma (HCC) which is 3-5-fold more common in men] was related to the inhibition of macrophage-derived IL-6 production by estradiol-17β (E2). In many circumstances, locally produced IL-6 reached the peripheral circulation and elicited systemic effects such as cachexia and paraneoplastic syndrome (including fever, increased erythrocyte sedimentation rate, increased levels of C-reactive protein in serum, hypoalbuminemia). This review highlights the EMT produced by IL-6 in cancer cells, as well as mechanisms underlying sex bias in HCC, enhanced IL-6 expression in cancer cells resulting from mutations in p53, consequent alterations in STAT3 transcriptional signaling, and the newer understanding of STAT3 nuclear bodies in the cancer cell as phase-separated biomolecular condensates and membraneless organelles (MLOs). Moreover, the perplexing issue of discrepant measurements of IL-6 in human circulation using different assays, especially in patients undergoing immunotherapy, is discussed. Additionally, the paradoxical chaperone (enhancing) effect of anti-IL-6 “neutralizing” antibodies on IL-6 in vivo and consequent limitations of immunotherapy using anti-IL-6 mAb is considered.

Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome

BackgroundPatients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats.MethodsAfter puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting.ResultsWe found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females.ConclusionsThe characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases.

Primary Localized Cutaneous Nodular Amyloidosis and Limited Cutaneous Systemic Sclerosis: Additional Cases with Dermatoscopic and Histopathological Correlation of Amyloid Deposition

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition due to the plasma cell proliferation and skin deposition of immunoglobulin light chains, without systemic amyloidosis or hematological dyscrasias. The association with autoimmune connective tissue diseases has been reported, especially with Sjogren’s syndrome, and in a few cases with systemic sclerosis. Herein, we describe three cases of PLCNA occurring in women with a diagnosis of limited cutaneous systemic sclerosis and review the literature on the topic to highlight a stereotypical presentation. Moreover, we support the usefulness of dermoscopy, characterized by a yellow–orange waxy pattern surrounded by telangiectasias, for a rapid and non-invasive diagnostic assessment. Thus, when asymptomatic nodules occur on lower limbs of women affected with limited systemic sclerosis, and dermoscopy identifies yellow–orange blotches, a diagnosis of PLCNA can be considered and further confirmed by histopathology. Monitoring for systemic amyloidosis development is advisable, although the risk of progression is considered very low.

The Two-Step Approach to Haploidentical Hematopoietic Stem Cell Transplantation (HI HSCT): 15 Years of Transplants in Patients 19-78 Years Old

Background/Methods: The two-step approach to HI HSCT was developed in 2005 with the first patient treated on clinical trial in early 2006. In this approach, after myeloablative [MA- 12 Gy total body irradiation (TBI)], reduced intensity (RIC- fludarabine, 2 Gy TBI and cytarabine, OR thiotepa, OR busulfan), or nonmyeloablative (NMA-fludarabine and 2 Gy TBI) conditioning, patients receive a fixed dose of unmanipulated donor lymphocytes (DLI) containing 2 x 108/kg CD3+ cells (Step 1). Two days later, cyclophosphamide (CY) 60 mg/kg/day x 2 is infused for bidirectional T cell tolerization. One day after the completion of CY, a CD34-selected stem cell product is infused (Step 2). All patients receive tacrolimus and mycophenolate mofetil starting at d-1. The two-step approach avoids stem cell exposure to CY, allows a growth factor-naïve fixed dose of donor T-cells to be infused increasing uniformity for outcomes analysis, and permits easier manipulation of both T-cell and CD34 cell dosing. In later protocols, the timing of the DLI after conditioning and the CD34 cell dose have been manipulated with the goal of reducing relapse, and age-based comorbidity and performance status indices were added to eligibility criteria to reduce non-relapse mortality (NRM). Results: We analyzed all 283 patients treated on a two-step HI HSCT clinical trial at our institution. The median follow-up is 63 (range 1-165) months. Diagnoses were AML (n=118), MDS (n=43), myeloproliferative disorder (n=7), CMML (n=3), B-ALL (n=21), Ph+ ALL (n=15), multiple myeloma (n=14), T cell ALL (n=9), aggressive lymphoma (n=15), CLL (n=8), Hodgkin (n=7), aplastic anemia (n=5), and lymphoma-other (n=18). Patients had high (45%), intermediate (43%), very high (5%), and low (4%) risk disease per the Revised Disease Risk Index. Median age of the group is 58 (19-78) years and 21% of patients were &amp;gt;age 65. Conditioning was MA in 56%, RIC in 37%, and NMA in 7%. All patients received 2 x 108/kg CD3+ cells in step 1 of the HSCT except for 1 early patient who received 1.7 x 108/kg CD3+ cells. Median CD34 cell dose was 6.3 (range 1.0-20.0) x 106/kg, median non-CY-exposed T cells in the CD34 product was 2.88 (range 0.33-50.0) x 103/kg. Patients developed a haploimmunostorm manifested by high grade fever, diarrhea and rash within 24 hours of receiving DLI. These symptoms effectively resolved after the administration of CY. Median peak fever of patients during the haploimmunostorm was 103.6 (range 98.6-106.1). No patients died as a consequence of the haploimmunostorm. Cumulative incidence (CI) of donor engraftment was 97%. Median time to neutrophil and platelet engraftment was 11 (8-21) days and 17 (10-173) days respectively. All results at 2 years: CI of relapse and NRM were 25% each. CI grades 2-4 and 3-4 acute GVHD were 39% and 7% respectively, and CI chronic GVHD was 15%. Probability of survival (OS) was 55% in the total cohort and 34% in patients &amp;gt;65 years. In patients with AML which represented the largest subgroup of patients, OS was 51% in the total cohort and 40% in patients &amp;gt; 65. Conclusion: HI HSCT using the two-step approach is an effective treatment for a variety of hematologic malignancies and dyscrasias. Despite older age, over 1/3 of patients &amp;gt;65 years were alive 2 years after HI-HSCT. Disclosures Flomenberg: Tevogen: Consultancy, Honoraria.

Laboratory monitoring during antifungal treatment of paediatric tinea capitis.

Griseofulvin and terbinafine are considered effective first-line therapies for tinea capitis (TC). Haematological dyscrasias and hepatic injury are possible adverse effects with both drugs. There is a debate in the literature regarding the necessity of laboratory monitoring during griseofulvin and terbinafine treatment. We aimed at assessing the prevalence and severity of haematological and hepatic laboratory test abnormalities in a paediatric cohort of African immigrants in Tel-Aviv with TC who were treated with Terbinafine or Griseofulvin. We conducted a retrospective study of all TC cases diagnosed and treated at the paediatric dermatology clinic, Tel-Aviv Medical centre, between June 2013 and March 2019. Epidemiologic, clinical and laboratory data were collected. Our cohort included 321 patients of whom 225 (70%) were treated with Griseofulvin and 96 (30%) with Terbinafine. We identified a total of 64 (20%) patients with haematological or hepatic laboratory test abnormalities that in most cases (96.3%) were considered as mild. No difference in laboratory abnormalities prevalence was identified between the griseofulvin and terbinafine groups (21.3% and 16.6%, respectively). Only one patient treated with Griseofulvin revealed significantly increased levels of hepatic aminotransferases that required discontinuation of treatment. Mild elevation in hepatic transaminases is relatively common among paediatric patients treated with systemic antifungal treatment for TC. However, significant laboratory abnormalities are extremely rare and may be diagnosed and addressed early through periodic laboratory tests monitoring.

Total Lymphoid Irradiation in The Treatment and Prevention of Pediatric Cardiac Allograft Rejection — A 23-Year Experience

Despite the development of increasingly efficacious immunosuppressive agents, allograft rejection is still a leading cause of morbidity and mortality in pediatric heart transplant patients. Total lymphoid irradiation (TLI) has emerged as a secondary treatment for recurrent cardiac allograft rejection refractory to medication in adults. However, there is limited evidence for long-term TLI efficacy and safety in the pediatric cohort. Our objectives were to evaluate 1) the long-term effects of TLI in treating recurrent pediatric cardiac allograft rejections at a single institution, and 2) the outcome of a unique prophylactic TLI protocol for re-transplant cardiac allograft in pediatric patients. This study included pediatric cardiac transplant patients who received TLI between 1996 and 2014, and who underwent regular right ventricular endomyocardial biopsies. TLI of 800 cGy in 10 fractions was delivered twice a week to the mantle and periaortic/splenic fields. Indication of TLI for treatment of allograft rejection included recurrent episodes (≥ 3) of rejection (defined as ISHLT Grade ≥ 1B/1R) or rejection episodes that failed to respond to medical therapy. Prophylactic TLI was indicated for patients who received a re-transplant cardiac allograft. Follow-up on these patients ended on January 23, 2020, comprising of 23 years of single institutional data. Comparisons in endpoints were performed using paired-sample, non-parametric tests. Eighteen patients underwent TLI for treatment of recurrent cardiac allograft rejection (n = 11, treatment cohort) and/or for rejection prevention in a re-transplant graft (n = 10, prophylactic cohort). Three patients completed 2 courses of TLI for both treatment and prevention of graft rejection. Median follow up was 10.1 years (range 0.5-23 years). In the treatment cohort, TLI demonstrated a trend to prolong the time to graft rejection, from a median of 62 days before TLI to 320 days after TLI (p = 0.054). In the prophylactic cohort, TLI increased ten-year graft survival from 11.1% to 44.4% (n = 9 due to a patient lost to follow-up; p = 0.38). Nine out of 10 patients underwent re-transplant due to graft coronary artery disease in the initial allograft – 1 patient developed coronary vessel narrowing in the re-transplant graft requiring a drug-eluting stent 17.1 years after prophylactic TLI, while the other 8 patients had no evidence of any narrowing, stenosis, or coronary allograft vasculopathy (CAV) in the re-transplant graft (mean CAV-free graft survival 9.4 years). During long-term follow-up, there was no incidence of hematological malignancies or blood dyscrasias. Our study showed that TLI was well tolerated and safe in long-term follow-up. It not only demonstrated a trend to prolong the time to graft rejection, but also showed promising results in preventing CAV and lengthening graft survival if given prophylactically. Further investigation into the role of treatment and prophylactic TLI is warranted.

A pharmacist's review of the treatment of systemic light chain amyloidosis.

Systemic light-chain (AL) amyloidosis is an uncommon hematologic plasma cell dyscrasia that is becoming increasingly recognized. Therapeutic agents used in AL amyloidosis overlap with those used in multiple myeloma; however, differences in disease features change treatment efficacy and tolerance. Pharmacists must be cognizant of these distinctions. Herein, this review article provides an up-to-date guide to treatment considerations for systemic AL amyloidosis in both the front-line and relapsed settings.Data sources: A comprehensive literature search was performed using the PubMed/Medline database for articles published through (June 2020) regarding treatments for AL amyloidosis. Search criteria included therapies that are FDA approved for multiple myeloma, as well as investigational agents. This review of chemotherapeutic agents reflects the current clinical practice guidelines endorsed by NCCN along with commentary based on the experience of pharmacists from a tertiary-referral center treating many patients with AL amyloidosis. Data consists of randomized controlled trials, observational cohorts, case reports, and ongoing clinical trials.Data summary: Frontline options discussed here include high-dose melphalan with autologous stem cell transplantation and bortezomib-based regimens. Regarding the relapsed setting, supporting data are compiled and summarized for: bortezomib, ixazomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, elotuzumab, isatuximab, venetoclax, NEOD001, and melflufen. The treatment platform for AL amyloidosis is expanding with novel agents traditionally used in multiple myeloma being adopted and modified for use in AL amyloidosis. The pharmacist's familiarity with the clinical evidence base for these agents and how they fit into standard protocols for AL amyloidosis is critical as dosing and monitoring recommendations are unique from multiple myeloma.

Etiology of priapism in the community: local factors can help guide prevention and savings

Background: Current understanding of the etiology and epidemiology of priapism includes idiopathic causes, certain medications and hematologic dyscrasias. In this study, we compare existing literature to more common etiologies of priapism at our institution. We aimed to assess the similarities and differences between the etiologies of priapism at our institution compared to the current literature and determine if the cause of priapism could be community specific.

Unexpected Ca2+-mobilization of oxaliplatin via H1 histamine receptors

Oxaliplatin is a widely used chemotherapeutic drug and represents the cornerstone of colorectal cancer therapy, in combination with 5-fluorouracil and folinic acid. As with many chemotherapeutic agents, its use is associated with a number of side effects, ranging from hypersensitivity reactions to haematological dyscrasias. Oxaliplatin also induces acute and chronic peripheral neuropathy.While it is likely that the haematological side effects are associated with its anti-proliferative effects and with the ability to form DNA adducts, the molecular mechanisms underlying peripheral neuropathy and hypersensitivity reactions are poorly understood, and therefore the choice of adequate supportive therapies is largely empirical.Here we show that an acute low dose oxaliplatin application on DRG neurons is able to induce an increase in intracellular calcium that is dependent on the Histamine 1 receptor (H1). Oxaliplatin-induced intracellular calcium rises are blocked by two selective H1 antagonist, as well as by U73122, a PLC inhibitor, and by 2-APB, a non-specific IP3 receptor blocker. Moreover, expression of the H1 receptor on HEK293 t cells unmasks an oxaliplatin-induced Ca2+-rise. Last, activation of H1 via either histamine or oxaliplatin activates TRPV1 receptors, a mechanism that has been associated with itch. These data, together with literature data that has shown that anti-histamine agents reduce the incidence of oxaliplatin-induced hypersensitivity, may provide a molecular mechanism of this side effect in oncological patients.

Which patients with ischaemic priapism require further investigation for malignancy?

Ischaemic priapism (IP) is characterised by a persistent, painful penile erection lasting for >4 h. Many causes of IP have been identified including haematological dyscrasias (particularly, sickle cell disease), drugs and rarely malignancy. There are also a large proportion of men, in which no aetiology is identified. Identification of men at risk for malignancy provides a diagnostic challenge to the clinicians looking after these patients. All cases of IP between 2007 and 2017 at a single tertiary andrology unit were identified. The case notes and electronic records of these patients were reviewed to identify cases of malignant priapism. Men with idiopathic IP were used as a control group for comparative statistics. In total, 412 men with IP were identified, 202 of which had idiopathic IP. Within this group, the prevalence of malignant priapism was 3.5% (n = 11). MP secondary to local invasion or penile metastases occurred in seven of the 11 men (bladder × 3, prostate, lung, urethral and chondrosarcoma of the pelvis). MP secondary to haematological malignancy occurred in the remaining four (chronic myeloid leukaemia × 2, chronic lymphocytic leukaemia, and myelodysplasia). IP was the initial presentation of malignancy in seven of the patients (64%). An abnormally low haemoglobin value (reference range 130-180 g/dl) was found in 82% (n = 9) of the men with MP. The mean haemoglobin value in men with MP was 109.64 ± 20.30 g/dl compared to the control of 131.87 ± g/dl. This difference was considered highly significant p = 0.0046. Men with MP also appear to have a very poor prognosis with an 18-month mortality of 64% (n = 7). Malignancy is a rare and important cause of IP. A low haemoglobin is a predictor of malignancy and warrants further investigation in IP.