Treatment of patients with Waldenström macroglobulinaemia: clinical practice update from the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of IgM paraprotein, bone marrow infiltration by clonal small B lymphocytes with plasmacytic differentiation and the MYD88 L265P mutation in >90% of cases. Traditionally, WM has been treated with chemoimmunotherapy. Recent trials have demonstrated the efficacy and safety of Bruton tyrosine kinase inhibitors in WM, both as monotherapy and in combination with other drugs. There is emerging evidence on the use of other agents including B-cell lymphoma 2 inhibitors and on the treatment of rare presentations of WM. In this update, the Medical and Scientific Advisory Group of Myeloma Australia reviews the available evidence on the treatment of WM since the last publication in 2017 and provides specific recommendations to assist Australian clinicians in the management of this disease.

Automated digital enumeration of plasma cells in bone marrow trephine biopsies of multiple myeloma.

AIMS: Determination of the number of plasma cells in bone marrow biopsies is required for the diagnosis and ongoing evaluation of plasma cell neoplasms. We developed an automated digital enumeration platform to assess plasma cells identified by antigen expression in whole bone marrow sections in multiple myeloma, and compared it with manual assessments. METHODS: Bone marrow trephine biopsy specimens from 91 patients with multiple myeloma at diagnosis, remission and relapse were stained for CD138 and multiple myeloma oncogene 1 (MUM1). Manual assessment and digital quantification were performed for plasma cells in the entire trephine section. Concordance rates between manual and digital methods were evaluated for each antigen by intraclass correlation analyses (ICC) with associated Spearman's correlations. RESULTS: The digital platform counted 16 484-1 118 868 cells and the per cent CD138 and MUM1-positive plasma cells ranged from 0.05% to 93.5%. Overall concordance between digital and manual methods was 0.63 for CD138 and 0.89 for MUM1. Concordance was highest with diffuse plasma cell infiltrates (MUM1: ICC=0.90) and lowest when in microaggregates (CD138: ICC=0.13). Manual counts exceeded digital quantifications for both antigens (CD138: mean=26.4%; MUM1: mean=9.7%). Diagnostic or relapse threshold counts, as determined by CD138 manual assessments, were not reached with digital counting for 16 cases (18%). CONCLUSIONS: Automated digital enumeration of the entire, immunohistochemically stained bone marrow biopsy section can accurately determine plasma cell burden, irrespective of pattern and extent of disease (as low as 0.05%). This increases precision over manual visual assessments which tend to overestimate plasma burden, especially for CD138, and when plasma cells are in clusters.

Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party.

PURPOSE: Early mortality in multiple myeloma (MM) is usually attributed to combined effects of active disease and comorbid factors. We have studied early deaths in a series of large multicenter trials to assess direct causes of death, their predictability, and whether current management strategies have reduced their frequency. PATIENTS AND METHODS: A total of 3,107 newly diagnosed patients entered onto United Kingdom Medical Research Council MM trials from 1980 to 2002 were studied. Trial files, final clinical summaries, and postmortem reports were analyzed. RESULTS: Death within 60 days of trial entry occurred in 299 patients (10%). Logistic regression modeling identified beta 2-microglobulin, performance status, and age as the most important predictors of early death, but only with 61% sensitivity and 73% specificity. Forty-five percent of deaths were attributable to infection, which was often associated with bone pain (particularly thoracic pain) and delay in presenting to medical care. Neutropenia was present at diagnosis in only 11 of the 135 deaths from infection. Renal failure was present in 28% of early deaths and was linked to light-chain MM, hypercalcemia, dehydration, and nonsteroidal anti-inflammatory drugs. There was no time related reduction in the percentage or nature of early deaths in 1,550 patients older than 65 years receiving similar therapy between 1982 and 2002. CONCLUSION: A tenth of patients die within 60 days of diagnosis of MM. Infection and renal failure are the main direct causes of early mortality, which cannot be accurately predicted by presenting prognostic features. All patients should be considered at high risk of death during induction therapy.

Postpartum anti-D: can we safely reduce the dose?

OBJECTIVE: To assess the potential for dose-reduction of prophylactic anti-D postpartum. DESIGN: Retrospective audit of fetomaternal haemorrhage (FMH) quantitation by flow cytometry. PARTICIPANTS AND SETTING: 5148 consecutive Rhesus D-negative women aged 15-45 years who had FMH estimation by flow cytometry at a central laboratory in Western Australia in the 65 months between 1 August 1999 and 31 January 2005. MAIN OUTCOME MEASURES: Quantitation of FMH volume for adequate prophylactic anti-D administration in a timely fashion. RESULTS: 90.4% (4651/5148) of the women had an FMH volume of 1.0 mL or less of Rh D-positive red cells, and 98.5% (5072/5148) had a volume of less than 2.5 mL. Only 0.4% of cases had an FMH volume of 6.0 mL or greater (range, 6.0-92.4 mL). CONCLUSIONS: This large retrospective audit shows that a currently available dose of 250 IU (50 mg) of anti-D would have been sufficient for 98.5% of the 5148 Rh D-negative women. On the basis of this evidence, a reduction in the recommended routine postpartum dose of anti-D from 625 IU to 250 IU when flow cytometric quantitation for FMH is available should be considered. Adopting such a strategy would ensure the ongoing provision of a valuable human blood product currently in limited supply.