Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study.

BACKGROUND: A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare. METHODS: We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT. RESULTS: With a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality. CONCLUSIONS: Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

Establishment of a Clinical Pharmacist-Led Multiple Myeloma Clinic with Collaborative Prescribing Model at the National Center for Cancer Care and Research in Qatar.

BACKGROUND: Multiple Myeloma (MM) is a chronic and incurable hematologic malignancy that is prevalent among the elderly. Interprofessional patient care showed superiority over physician-only care in multiple settings, including MM. OBJECTIVE: The primary objective of this study was to evaluate the impact of CP-led clinic and CPs interventions on MM patient care. PRACTICE DESCRIPTION: Real-world analysis of ambulatory patients with MM showed that clinical pharmacists (CPs) were central to the optimization of therapy and adherence to treatment schedules and supportive medications. PRACTICE INNOVATION: The CP-led MM Clinic was established with a collaborative prescribing agreement (CPA) in 2022 at the National Center for Cancer Care and Research (NCCCR) in Qatar and was the first of its kind in the MENA region. This CPA allowed CPs to issue refills for supportive medications and order required laboratory tests. EVALUATION METHODS: Data collected included the number of CP interventions, refills ordered by CPs, documentation of patient education, and medication reconciliations. The data were retrospectively collected and analyzed comparing ambulatory patients with MM treated before (2021) to those treated after the clinic implementation in 2022. RESULTS: The study population comprised 20 patients. A higher number of CPs interventions were documented post-clinic than pre-clinic (343 vs. 76, P=0.004), with earlier initiation of bisphosphonate post-clinic (25 vs. 206 days, P = 0.008). There were also significant improvements in the introduction of risk appropriate venous thromboembolism (VTE) prophylaxis (43% vs. 6%, P=0.001) as well as vitamin D and calcium supplementation (100% vs. 68%, P=0.02) post-clinic. Twenty-two medication refills for supportive medications and eight pre-chemotherapy laboratory investigations were ordered by CPs. CONCLUSION: The CP-led clinic provided a timely link to care optimization for ambulatory MM patients. This innovative CPA model implemented in the clinic could potentially be applied to different cancer settings to optimize safe and effective patient care.

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances.

In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.

Evidence-based Management of Chronic Lymphocytic Leukemia: Consensus Statements from the Gulf Region.

INTRODUCTION: Despite recent advances in diagnosis, prognostication, and treatment options, chronic lymphocytic leukemia (CLL) is still a largely incurable disease. New concepts on diagnosis, staging, treatment, and follow-up on CLL have been incorporated throughout recent years. The lack of regional consensus guidelines has led to varying practices in the management of patients with CLL in the region. AIM: This manuscript aims to reach a consensus among expert hematologists regarding the definitions, classifications, and related practices of CLL. The experts developed a set of statements utilizing their personal experience together with the current literature on CLL management. This consensus aims to provide guidance for healthcare professionals involved in the management of CLL and serves as a step in developing regional guidelines. METHODS: Eight experts responded to 50 statements regarding the diagnosis, staging, treatment, and prognosis of CLL with three potential answering alternatives ranging between agree, disagree, and abstain. This consensus adopted a modified Delphi consensus methodology. A consensus was reached when at least 75% of the agreement to the answer were reached. This manuscript presents the scientific insights of the participating attendees, panel discussions, and the supporting literature review. RESULTS: Of the 50 statements, a consensus was reached on almost all statements. Statements covered CLL-related topics, including diagnostic evaluation, staging, risk assessment, different patient profiles, prognostic evaluation, treatment decision, therapy sequences, response evaluation, complications, and CLL during the COVID-19 pandemic. DISCUSSION/CONCLUSION: In recent years, CLL management has progressed significantly with many diagnostic tests and several novel treatments becoming available. This consensus gathers decades of consolidated principles, novel research, and promising prospects for the management of this disease.

Applying value-based strategies to accelerate access to novel cancer medications: guidance from the Oncology Health Economics Expert Panel in Qatar (Q-OHEP).

BACKGROUND: In line with global trends, cancer incidence and mortality may have decreased for specific types of cancer in Qatar. However, the cancer-related burden on patients, healthcare systems, and the economy is expected to expand; thus, cancer remains a significant public healthcare issue in Qatar. Qatar's free access to cancer care represents a considerable economic burden. Ensuring the best utilization of financial resources in the healthcare sector is important to provide unified and fair access to cancer care for all patients. Experts from the Qatar Oncology Health Economics Expert Panel (Q-OHEP) aimed to establish a consistent and robust base for evaluating oncology/hematology medications; involve patients' insights to accelerate access to cutting-edge medications; increase the value of cancer care; and reach a consensus for using cost-effective strategies and efficient methodologies in cancer treatment. METHODS: The Q-OHEP convened on 30 November 2021 for a 3-hour meeting to discuss cancer management, therapeutics, and health economics in Qatar, focusing on four domains: (1) regulatory, (2) procurement, (3) treatment, and (4) patients. Discussions, guided by a moderator, focused on a list of suggested open-ended questions. RESULTS: Some of the salient recommendations included the development of a formal, fast-track, preliminary approval pathway for drugs needed by patients with severe disease or in critical condition; and encouraging and promoting the conduct of local clinical trials and real-world observational studies using existing registry data. The Q-OHEP also recommended implementing a forecast system using treatment center data based on the supply/demand of formulary oncology drugs to detect treatment patterns, estimate needs, expedite procurement, and prevent shortages/delays. Furthermore, the panel discussed the needs to define value concerning cancer treatment in Qatar, implement value-based models for reimbursement decision-making such as health technology assessment and multiple-criteria decision analysis, and promote patient education and involvement/feedback in developing and implementing cancer management guidelines. CONCLUSION: Herein, we summarize the first Q-OHEP consensus recommendations, which aim to provide a solid basis for evaluating, registering, and approving new cancer medications to accelerate patient access to novel cancer treatments in Qatar; promote/facilitate the adoption and collection of patient-reported outcomes; and implement value-based cancer care in Qatar.

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study.

OBJECTIVE: To compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing-remitting multiple sclerosis. METHODS: Patients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly. RESULTS: The Kaplan-Meier estimates of the primary outcome measure 'no evidence of disease activity' was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005. CONCLUSIONS: In this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity'. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.

Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia.

Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 × 109/L were randomized 1:1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with ≥10% occurrence in the eltrombopag vs placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to acute myeloid leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02158936.

A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine.

OBJECTIVES: Thrombocytopenia is an independent adverse prognostic factor in patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment for the majority of patients with higher-risk MDS, is associated with aggravated thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin receptor agonist, which also has been shown to inhibit proliferation of leukaemia cell lines in vitro. This phase I clinical trial was designed to explore the safety and tolerability of combining eltrombopag with azacitidine in patients with MDS. In addition, we assessed the potential effects of eltrombopag on hematopoietic stem and progenitor cells (HSPCs) from included patients. PATIENTS AND METHODS: Previously untreated patients with MDS eligible for treatment with azacitidine and with a platelet count <75 × 10(9) /L were included. Patients received eltrombopag in dose escalation cohorts during three cycles of azacitidine. RESULTS: Twelve patients, with a median age of 74 yr, were included. Severe adverse events included infectious complications, deep vein thrombosis and transient ischaemic attack. The maximal tolerated eltrombopag dose was 200 mg qd. Complete remission or bone marrow remission was achieved in 4 of 12 patients. Platelet counts improved or remained stable in 9 of 12 patients despite azacitidine treatment. No increase in blast count, disease progression, or bone marrow fibrosis related to study medication was reported. Eltrombopag did not induce cycling of HSPCs. CONCLUSION: The combination of eltrombopag with azacitidine in high-risk MDS patients is feasible and well tolerated. Improvements in platelet counts and the potential antileukaemic effect of eltrombopag should be explored in a randomised study.

Post-Thymectomy Autoimmune Flare-Up With New-Onset Type 1 Diabetes Mellitus.

The thymus gland aids in the maturation of the immune system. An overactive or malfunctioning thymus gland, as seen in thymomas, can lead to disrupted immune systems. Thymectomy, the usual treatment, can paradoxically lead to further derangements in the immune system, leading to new autoimmune disorders. Most of these reported disorders are rheumatological. Except preclinical studies, there are no reported cases of autoimmune diabetes post-thymectomy. A 25-year-old woman who had malignant thymoma underwent chemotherapy, followed by thymectomy and radiotherapy. She developed autoimmune diabetes mellitus (AID) approximately 1 year post-thymectomy, evident from raised glycated hemoglobin, anti-glutamic acid decarboxylase (GAD) antibodies, ineffectiveness of oral glucose-lowering agents, and positive response to insulin. AID can occur after thymectomy, as evidenced by animal studies and this case report. Whether these patients would have long-term outcomes and control of diabetes differently than classic type 1 diabetes mellitus (T1D) is uncertain. Further research is needed to prove causality between thymectomy and diabetes.

Management of adult acute lymphoblastic leukemia in the Gulf Cooperation Council (GCC) countries: A consensus report from the GCC Adult ALL Working Group.

Leukemia burden is growing in the Gulf Council Cooperation (GCC) countries. Nonetheless, there is no unified protocol for managing adult acute lymphoblastic leukemia (ALL) patients in the GCC-countries. Therefore, the GCC Adult-ALL Treaters working group developed this consensus to address the adult-ALL treatment protocols in the GCC-countries and related toxicities' management. Besides, the consensus aimed to highlight the current unmet needs and treatment gaps and provide recommendations to optimize adult-ALL care and patient-centered communication. A three-step modified Delphi method to develop evidence-based recommendations through two-voting rounds and in-between virtual meetings are used in the manuscript development. A 12 experts' panel from five GCC-countries and two international experts were invited to participate in this consensus. This consensus consisted of 35-statements that highlighted the experts' recommendations to optimize ALL adults' care in the first line setting and manage pediatric or pediatric-inspired regimens-related toxicities. Besides, guidance was provided for future research direction and improve patient-centered communication. In conclusion, the adult-ALL management landscape is evolving, and the current evidence highlights better response and survival outcomes with pediatric or pediatric-inspired regiments. Therefore, protocols are needed to optimize the adult-ALL management in the GCC and tailored clinical-trials findings according to the GCC patients' characteristics and local-healthcare infrastructure.

Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Adjuvanted influenza a (H1N1) 2009 vaccine in patients with hematological diseases: good safety and immunogenicity even in chemotherapy-treated patients.

BACKGROUND: Patients with hematological malignancies are more susceptible to viral infections including influenza. In 2009, the World Health Organization classified the novel influenza A (H1N1) virus as pandemic. The potential impact of this pandemic for patients with hematological disorders was unknown. Institutional guidelines recommended two doses of AS03-adjuvanted influenza A (H1N1) 2009 pandemic vaccine for these patients. OBJECTIVES: We aimed to determine the safety, immunogenicity, and clinical efficacy of this vaccine in patients with hematological diseases. Furthermore, we compared the immunological responses to that obtained by the non-adjuvanted trivalent seasonal influenza vaccine (TIV). METHODS: All included patients received adjuvanted pandemic vaccine and the majority received TIV. Serum for antibody analyses was collected at five time points. RESULTS: Thirty-one patients with different hematological diseases were included. After the second vaccine dose, a total of 25 (81%) reached both protective levels of antibodies and seroconversion response. Antibody titers ≥ 1 : 40 persisted for 50% of responding patients at 1 yr. Seroconversion was observed in 69% of 14 patients who had undergone hematopoietic stem cell transplantation and in all (9/9) patients with myeloma (five with ongoing treatment including high-dose corticosteroids). After vaccination with TIV, seroconversions against the three included strains were detected in 28%, 40%, and 20%. Response to the adjuvanted pandemic vaccine was superior (P < 0.009). CONCLUSIONS: A substantial proportion of patients with hematological malignancies including patients undergoing chemotherapy mounted a good response to the adjuvanted pandemic vaccine. This vaccine had superior immunogenicity as compared to the non-adjuvanted TIV.

Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia who suffer from recurrent infections can be offered prophylactic intravenous immunoglobulin (Ig) substitution. Our aim was to assess the prevalence of pure IgG subclass deficiency (with normal Ig levels), its correlation to risk of infection, and the clinical value of routine measurement of serum IgG subclass levels in patients with CLL. METHODS: Serum levels of Ig and IgG subclasses were determined in patients with CLL at Uppsala University Hospital. Clinical data were collected through patient records and questionnaires. RESULTS: Hypogammaglobulinemia occurred in 52.3% out of 111 patients. These patients did not have a higher annual risk of infection than patients without hypogammaglobulinemia (79.5% vs 79.1%, p = 0.706 for all infections; 13.4% vs 11.2%, p = 0.394 for severe infection; and 1.7% vs 3.4%, p = 0.083 for sepsis). Pure subclass deficiency was uncommon and occurred in 6 patients (5.4%). The annual overall risk of infection, of severe infection, and of sepsis for these patients did not differ as compared to patients with no hypogammaglobulinemia and no subclass deficiency (70.8% vs 80.7%, p = 0.334; 11.8% vs 11.1%, p = 0.497; and 8.9% vs 2.3%, p = 0.067, respectively). CONCLUSIONS: Pure IgG subclass deficiency is rare in patients with CLL. In this heterogeneous cohort of patients, neither hypogammaglobulinemia nor pure IgG subclass deficiency were significant risk factors for infectious complications. Measurement of serum levels of Ig may be justified in patients with recurrent severe infections, but routine analysis of IgG subclass levels in patients with CLL is probably not warranted.

Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection.

BACKGROUND: Prolonged chemotherapy-induced neutropenia is a major risk factor for the development of severe bacterial and fungal infections. Infectious manifestations may progress despite adequate anti-infectious treatment and lead to a very high short-term mortality. Granulocyte transfusion (GT) therapy is often considered. However, its efficacy is not well documented. METHODS: We retrospectively analyzed the clinical characteristics and outcome of a cohort of patients with haematological malignancies receiving GT during neutropenia and severe infection. RESULTS: A total of 30 patients with a median age of 46 y (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%) and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All patients had severe and prolonged (median 16 days) neutropenia. The major indications for GT were persistent fever and clinical deterioration despite broad anti-infectious therapy, in combination with progressive pneumonia (n = 16), neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were given for a median of 3 transfusions (range 1-14). The median time to fever defervescence after GT was 14 days (range 6-33 days). For 11 patients, the resolution of fever and all signs of infection could directly be related to GT, and 3 of these patients became long-term survivors. Mortality at 30 days post-GT was 40% and at 6 months post-GT was 72%. GT was well tolerated. CONCLUSIONS: A substantial proportion of severely ill neutropenic patients appeared to benefit from GT. The results further underline the need for well- designed, randomized, prospective trials to determine the efficacy of this intervention in patients with life-threatening infectious complications.

CSF Concentrations of CXCL13 and sCD27 Before and After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: In the past decade, autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a treatment for relapsing-remitting multiple sclerosis (RRMS). How this procedure affects biomarkers of B- and T-cell activation is currently unknown. The objective of this study was to investigate CXCL13 and sCD27 concentrations in CSF before and after AHSCT. METHODS: This prospective cohort study was conducted at a specialized MS clinic in a university hospital. Patients with a diagnosis of RRMS, treated with AHSCT between January 1, 2011, and December 31, 2018, were evaluated for participation. Patients were included if CSF samples from baseline plus at least 1 follow-up were available on June 30, 2020. A control group of volunteers without neurologic disease was included as a reference. CSF concentrations of CXCL13 and sCD27 were measured with ELISA. RESULTS: The study comprised 29 women and 16 men with RRMS, aged 19-46 years at baseline, and 15 women and 17 men, aged 18-48 years, in the control group. At baseline, patients had higher CXCL13 and sCD27 concentrations than controls, with a median (IQR) of 4 (4-19) vs 4 (4-4) pg/mL (p < 0.0001) for CXCL13 and 352 (118-530) vs 63 (63-63) pg/mL (p < 0.0001) for sCD27. After AHSCT, the CSF concentrations of CXCL13 were considerably lower at the first follow-up at 1 year than at baseline, with a median (IQR) of 4 (4-4) vs 4 (4-19) pg/mL (p < 0.0001), and then stable throughout follow-up. The CSF concentrations of sCD27 were also lower at 1 year than at baseline, with a median (IQR) of 143 (63-269) vs 354 (114-536) pg/mL (p < 0.0001). Thereafter, sCD27 concentrations continued to decrease and were lower at 2 years than at 1 year, with a median (IQR) of 120 (63-231) vs 183 (63-290) pg/mL (p = 0.017). DISCUSSION: After AHSCT for RRMS, CSF concentrations of CXCL13 were rapidly normalized, whereas sCD27 decreased gradually over the course of 2 years. Thereafter, the concentrations remained stable throughout follow-up, indicating that AHSCT induced long-lasting biological changes.

Differentiation syndrome in patients with acute promyelocytic leukemia.

A 48-year-old male diagnosed with acute promyelocytic leukemia (APL) started on all-trans-retinoic acid and arsenic trioxide, developed typical symptoms of differentiation syndrome, and improved dramatically on steroids. Hence, any APL patient started on chemotherapy, needs to be monitored closely for developing differentiation syndrome and to start steroid upon suspicion.

Recurrent sideroblastic anemia during pregnancy.

Sideroblastic anemia is a heterogeneous group of disorders typified by the presence of ring sideroblasts in the bone marrow and has congenital and acquired types. Sideroblastic anemia is a rare event in pregnancy. We report a case of a 32-year-old female patient, gravida 4 para 3, 27th weeks pregnant, who presented to the emergency department complaining of palpitation and generalized weakness for 2 weeks. She was found to have severe normochromic normocytic anemia, with hemoglobin of 4.2 g/dl, and low reticulocytes count of 13 × 103/µl. She gave a history of recurrent anemia, which had only occurred during pregnancy. Her bone marrow aspirate showed many ring sideroblasts concluding the diagnosis of sideroblastic anemia (SA). Further investigation revealed a significantly low pyridoxine level (vitamin B6) of (8 nmol/L). The Hb level improved with vitamin B6 replacement, without any transfusion support.

Central catheter-related Gordonia bronchialis bacteremia in an immunocompromised patient: A case report, and literature review.

Gordonia is a rarely reported organism causing central line-associated bloodstream infection (CLABSI). This article reports an acute myeloid leukemia (AML) case in which the patient developed febrile neutropenia and was later found to have Gordonia bronchialis (G. bronchialis) CLABSI. The patient received a two-week ceftriaxone regimen, based on susceptibility. The microbiologic diagnosis of this organism is considered challenging due to its resemblance with other organisms; however, more sophisticated methods of diagnosis (such as gene sequencing) can aid in differentiation.

Next-generation sequencing of baseline genetic mutations and outcomes of eltrombopag and azacitidine therapy in patients with myelodysplastic syndromes and thrombocytopenia: Data from the SUPPORT clinical trial.

Eltrombopag has been previously shown to be effective in reversing azacitidine-mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate- to high-risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort were associated with treatment outcomes. Based on the available data, we observed no imbalance in the mutational profiles between treatment arms or a clear association between identified somatic mutations and clinical outcomes.

Hematological: Low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study.

BACKGROUND: Bacteremia is a major cause of morbidity and mortality in patients with hematological malignancies. OBJECTIVES: The aim of this study was to define temporal trends in species distribution, antimicrobial susceptibility, and all-cause mortality in bacteremic hospitalized patients receiving no antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A total of 677 clinical episodes of bacteremia were identified in 463 patients during 2002-2008, and the results were compared with those published from the same institution during 1980-86 and 1988-2001. No major changes in patient selection were introduced during this period. RESULTS: Between 2002 and 2008, the dominating pathogens were Escherichia coli (18%), coagulase-negative staphylococci (15%), viridans streptococci (14%), Klebsiella spp. (10%), and Enterococcus faecium (8%). The 7-d crude mortality rate was 5.2%. Polymicrobial bacteremia was seen in 25.7% of the patients who died within 7 d and in 13.1% of the survivors (P = 0.04). Acquired resistance was rarely observed, but a statistically significant increase in ciprofloxacin resistance in E. coli was observed. Comparing 2002-2008 with historical data from the same institution, the proportion of Gram-positive isolates remained stable at 53-55% from 1988. CONCLUSIONS: The avoidance of fluoroquinolone prophylaxis may have contributed to a stable proportion of Gram-positive bacteremia. The crude mortality was low in an international perspective. Acquired resistance was uncommon, but ciprofloxacin resistance in E. coli increased significantly. We believe that an indiscriminate use of antibacterial prophylaxis could be avoided in neutropenic patients without a negative impact on mortality.