In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT.

Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres.

Advances in the management of myeloma: an update.

Myeloma is an aggressive B-cell malignancy resulting from an uncontrolled production of plasma cells in the bone marrow. A multitude of drugs and combinations of drugs are now approved for use to treat this complex disease and nurses require knowledge and skills in recognising and managing new side effects associated with these treatments. This article presents an overview of some of the newer and recently approved drugs and the important side effects that have been associated with them.

Marrow changes and reduced proliferative capacity of mesenchymal stromal cells from patients with "no-option" critical limb ischemia; observations on feasibility of the autologous approach from a clinical trial.

Background Aims: Approximately 1 in 3 patients with critical limb ischemia (CLI) are not suitable for surgical or endovascular revascularization. Those "no-option" patients are at high risk of amputation and death. Autologous bone marrow mesenchymal stromal cells (MSCs) may provide a limb salvage option.

Serum protein and electrolyte imbalances are associated with chemotherapy induced neutropenia.

Introduction: Cancer and its treatment using various chemotherapeutic agents can have many adverse side effects. These side effects often result in significant changes in haematological and biochemical composition of blood. As a result, the regular monitoring of serum biochemical and haematological changes plays an important role in management of disease.

Mutations Identified Using NGS Comprise the Overwhelming Majority of Disruptions in CLL: Results From a Multicentre Study.

Limited data exists to show the correlation of (tumour protein 53) mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%).

Integrating artificial intelligence into haematology training and practice: Opportunities, threats and proposed solutions.

There remains a limited emphasis on the use beyond the research domain of artificial intelligence (AI) in haematology and it does not feature significantly in postgraduate medical education and training. This perspective article considers recent developments in the field of AI research in haematology and anticipates the potential benefits and risks associated with its deeper integration into the specialty. Anxiety towards the greater use of AI in healthcare stems from legitimate concerns surrounding data protection, lack of transparency in clinical decision-making, and erosion of the doctor-patient relationship.

Treatment patterns and outcomes of unfit and elderly patients with Mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis.

Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP).

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Background: Despite recent advances, outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) remain poor. Immune checkpoint inhibitors have shown limited efficacy in this setting, but combinations with novel agents may enhance benefit. Combination therapy with durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, and danvatirsen (AZD9150; an antisense oligonucleotide inhibiting signal transducer and activator of transcription 3 [STAT3]) or tremelimumab (an anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] antibody) may augment endogenous antitumor activity.

Keeping an Eye on Bisphosphonate Therapy in Myeloma: A Case Report of Ocular Inflammation Postzoledronic Acid Infusion.

Bisphosphonates have evolved over the past decades from oral to more potent intravenous preparations. Along with significant paradigm shift in the management of myeloma over the past years, stronger nitrogen-containing bisphosphonates, due to their antiresorptive action on the bones, have found their way as a key and integral part in the management of bone disease in myeloma. Multiple randomized controlled trials have established efficacy of bisphosphonates in reducing skeletal-related events in myeloma.

COVID-19 in adults: test menu for hospital blood science laboratories.

Introduction: Coronavirus disease 2019 (COVID-19), is a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Clinical Blood Sciences Laboratory (CBSL) plays a key role in supporting the monitoring and management of patients with COVID-19 disease.

Objective: To provide a comprehensive CBSL testing protocol to support the medical management of SARS-CoV-2 infection.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

Background: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need.

Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL.

Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled.

Molecular Profiling: A Case of Acute Promyelocytic Leukemia.

Several variant translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in APL and were sought by application of a next-generation sequencing approach to detect those recurrently found in myeloid malignancies.

A novel molecular assay using hybridisation probes and melt curve analysis for exon 9 mutation detection in myeloproliferative neoplasms.

Aims: Somatic insertions/deletions in exon 9 of the calreticulin gene have been identified in patients with essential thrombocythemia and primary myelofibrosis. Over 55 mutations have been discovered, 80% of which consist of either type 1 52-bp deletion or type 2 5-bp insertion. Other mutations (types 3-5) in conjunction with types 1 and 2 account for >87% of identified mutations.

Tumour Lysis Syndrome and Partial Remission Occurring After Administration of a Test Dose of Obinutuzumab.

Unlabelled: Chronic lymphocytic leukaemia (CLL) is one of the most common haematological malignancies worldwide, with an increasing prevalence in the elderly population. Obinutuzumab is a type II anti-CD20 monoclonal antibody which showed superiority over rituximab in combination chemotherapy with chlorambucil for the treatment of CLL in the CLL11 trial (NCT01010061) and is becoming part of standard first line treatment for CLL in the elderly based on its potent efficacy and benign safety profile. We report the case of a chemotherapy naive patient who develop tumour lysis syndrome despite appropriate prophylaxis, and had partial remission of her disease after receiving only the initial test dose of obinutuzumab.

Molecular heterogeneity of familial myeloproliferative neoplasms revealed by analysis of the commonly acquired JAK2, CALR and MPL mutations.

The myeloproliferative neoplasms (MPN) are clonal, hematological malignancies that include polycythemia vera, essential thrombocythemia and primary myelofibrosis. While most cases of MPN are sporadic in nature, a familial pattern of inheritance is well recognised. The phenotype and status of the commonly acquired JAK2 V617F, CALR exon 9 and MPL W515L/K mutations in affected individuals from a consecutive series of ten familial MPN (FMPN) kindred are described.

The novel tubulin-targeting agent pyrrolo-1,5-benzoxazepine-15 induces apoptosis in poor prognostic subgroups of chronic lymphocytic leukemia.

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL.

CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+.