Peripheral blood stem cell mobilisation following bortezomib, lenalidomide and dexamethasone induction for multiple myeloma: a real-world single-centre experience.

BACKGROUND: Bortezomib, lenalidomide and dexamethasone (VRd) is now the standard-of-care induction therapy for newly diagnosed transplant-eligible multiple myeloma patients, replacing bortezomib, cyclophosphamide and dexamethasone (VCD) therapy. Lenalidomide can negatively impact stem cell yield because of its myelosuppressive effects, although studies have shown that the latter can be overcome with the use of cyclophosphamide for peripheral blood stem cell (PBSC) mobilisation. AIMS AND METHODS: To investigate whether lenalidomide impacts on PBSC mobilisation and to evaluate the optimal mobilisation strategy post VRd induction, we performed a retrospective review of 56 myeloma patients at a single centre who had PBSC mobilisation between January 2019 and March 2021 and compared three cohorts: (i) VCD induction; mobilisation with granulocyte colony-stimulating factor (G-CSF) alone (n = 23); (ii) four cycles VRd induction; mobilisation with G-CSF and cyclophosphamide (G-CSF + Cyclo) (n = 20); and (iii) three cycles VRd induction; mobilisation with G-CSF alone (n = 13). RESULTS: There was no difference in the mean total CD34 count between VCD and VRd patients who had G-CSF mobilisation (6.27 × 106 /kg vs 5.50 × 106 /kg, P > 0.99). VRd patients mobilised with G-CSF + Cyclo achieved higher mean total CD34 counts compared with G-CSF alone (8.89 × 106 /kg vs 5.50 × 106 /kg, P = 0.04). The majority of VRd patients who had G-CSF + Cyclo (19 of 20; 95%) collected sufficient cells for two or more autologous stem cell transplants (ASCTs), regardless of whether this was required, compared with eight of 13 (62%) VRd patients who had G-CSF alone. CONCLUSION: We conclude that successful PBSC mobilisation for at least one ASCT is possible after three cycles of VRd induction using G-CSF alone. The upfront use of a cyclophosphamide-based mobilisation strategy has a role in patients who have had VRd induction, where the aim is to collect enough stem cells for two or more ASCTs.

The importance of frailty assessment in multiple myeloma: a position statement from the Myeloma Scientific Advisory Group to Myeloma Australia.

Multiple myeloma (MM) is a disease of older people, yet factors relating to comorbidity and frailty may threaten treatment tolerability for many of this heterogenous group. There has been increasing interest in defining specific and clinically relevant frailty assessment tools within the MM population, with the goal of using these frailty scores, not just as a prognostic instrument, but also as a predictive tool to allow for a frailty-adapted treatment approach. This paper reviews the various frailty assessment frameworks used in the evaluation of patients with MM, including the International Myeloma Working Group Frailty Index (IMWG-FI), the Mayo Frailty Index and the simplified frailty scale. While the IMWG-FI remains the most widely accepted tool, the simplified frailty scale is the most user-friendly in busy day-to-day clinics based on its ease of use. This paper summarises the recommendations from the Myeloma Scientific Advisory Group (MSAG) of Myeloma Australia, on the use of frailty assessment tools in clinical practice and proposes a frailty-stratified treatment algorithm to aid clinicians in tailoring therapy for this highly heterogeneous patient population.

Abnormal vaginal flora and spontaneous preterm birth in high-risk singleton pregnancies with cervical cerclage.

OBJECTIVE: To investigate abnormal vaginal and suture-based bacterial flora for associations with spontaneous preterm birth in high-risk singleton pregnancies with an ultrasound-indicated or emergency cervical cerclage. MATERIALS AND METHODS: A retrospective study of 196 singleton pregnancies with an ultrasound-indicated or emergency cerclage at the Royal Women's Hospital, Australia, from 2004 to 2018. High vaginal swabs were collected regularly between 14 and 26 weeks' gestation, including pre- and post-cerclage insertion, and sent for microscopy and culture. Cervical suture was cultured upon removal. Primary outcomes were spontaneous preterm birth <37, <34 and <30 weeks. RESULTS: 43.4% (85/196) of women delivered preterm. The acquisition and persistence of vaginal Escherichia coli following cerclage insertion were independently associated with spontaneous preterm birth <37 weeks (p = .0225, p = .0477). Escherichia coli growth from the cervical suture upon removal was associated with spontaneous preterm birth <34 weeks (p = .0458). The acquisition of vaginal mixed anaerobes post-cerclage was independently associated with spontaneous preterm birth <34 weeks (p = .0480). CONCLUSION: For singleton pregnancies with an ultrasound-indicated or emergency cerclage, the presence of vaginal or suture-based Escherichia coli following cerclage insertion yields increased risk of cerclage failure and spontaneous preterm birth.

The contemporary value of dedicated preterm birth clinics for high-risk singleton pregnancies: 15-year outcomes from a leading maternal centre.

OBJECTIVES: Preterm birth clinics provide dedicated obstetric care to women at high risk of spontaneous preterm birth (SPTB). There remains a lack of conclusive evidence to support the overall utility of such clinics, attributable to a paucity and heterogeneity of primary data. This study audits Australia's largest and oldest dedicated preterm birth clinic with the aim to add primary data to the area and offer opportunities for similar clinics to align practice. METHODS: A retrospective audit of referrals to the Preterm Labour Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2018 was conducted. 1,405 singleton pregnancies met inclusion criteria. The clinic's key outcomes, demographics, predictive tests and interventions were analysed. The primary outcomes were SPTB before 37, 34 and 30 weeks' gestation. RESULTS: The overall incidence of SPTB in the clinic was 21.2% (n=294). Linear regression showed reductions in the adjusted rates of overall SPTB and pre-viable SPTB (delivery <24 weeks) from 2004 (108%; 8%) to 2018 (65%; 2% respectively). Neonatal morbidity and post-delivery intensive care admission concurrently declined (p=0.02; 0.006 respectively). Rates of short cervix (cervical length <25 mm) increased over time (2018: 30.9%) with greater uptake of vaginal progesterone for treatment. Fetal fibronectin, mid-trimester short cervix, and serum alkaline phosphatase were associated with SPTB on logistic regression. CONCLUSIONS: Dedicated preterm birth clinics can reduce rates of SPTB, particularly deliveries before 24 weeks' gestation, and improve short-term neonatal outcomes in pregnant women at risk of preterm birth.

Peripheral blood stem cell mobilisation with G-CSF alone versus G-CSF and cyclophosphamide after bortezomib, cyclophosphamide and dexamethasone induction in multiple myeloma.

Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m2; high dose: 3-4 g/m2) PBSC mobilisation strategies in 288 patients who only received bortezomib, cyclophosphamide and dexamethasone (VCD) induction prior to autograft across six apheresis centres from November 2012 to June 2017. 'Uncomplicated successful mobilisation' was defined as achieving a PBSC yield of ≥4 × 106/kg within two aphereses, without plerixafor or mobilisation-associated toxicity (predominantly febrile neutropenia, FN). Success rates were 84% in G-cyclo standard dose (6% FN), 64% in G-cyclo high dose (18% FN) and 69% in G-alone (plerixafor successfully salvaged 8/9 patients). Median total stem cell yield was significantly higher with G-cyclo, but not different between the two cyclophosphamide doses. Age greater than the median of 61 years was associated with higher failure rates (22 vs. 11%, p = 0.01) and lower PBSC yield, especially in the G-alone group. Prior radiotherapy exposure did not impact on collection success. Our observations suggest that both G-cyclo standard dose and G-alone are reasonable mobilisation strategies. The former may be preferred if salvage plerixafor is unavailable.

Outcomes and predictive tests from a dedicated specialist clinic for women at high risk of preterm labour: A ten year audit.

BACKGROUND: Preterm birth continues to be a major cause of infant morbidity and mortality worldwide, but advances have recently been made in its prediction and prevention. A short cervix (<25 mm) in the second trimester on transvaginal ultrasound scan and fetal fibronectin are important predictive tests. For over ten years, the Preterm Labour Clinic at the Royal Women's Hospital, Melbourne, Australia has provided care for women at high risk of preterm birth, including those with a previous preterm birth, previous cervical surgery, uterine malformation or incidental finding of short cervix at routine ultrasound. The purpose of this study was to review this clinic's outcomes for the first decade. METHODS: This was a retrospective cohort study of all referrals to the Preterm Labour Clinic during the period 2004-2013 inclusive. Seven hundred and fifty-six cases met the study inclusion criteria of appropriate risk factor, singleton pregnancy, surveillance undertaken and outcome data available. RESULTS: The preterm birth rate (<37 weeks) was 21.4%. The rate of preterm birth by year decreased significantly when adjusted for risk (P = 0.002). A short cervix was diagnosed in 32% of the sample, and positively correlated with lower gestational age at delivery. Fetal fibronectin and serum alkaline phosphatase were independent predictors of preterm birth <34 weeks and <37 weeks. CONCLUSION: The adjusted preterm birth rate at the Royal Women's Hospital's Preterm Labour Clinic has decreased significantly over the decade studied. Positive fetal fibronectin at 26 weeks and elevated serum alkaline phosphatase are independent predictors of preterm birth.

Factors associated with spontaneous preterm birth risk assessed by transvaginal ultrasound following cervical cerclage.

OBJECTIVE: To determine the predictive value of various cervical length measurements postcerclage for the outcome of preterm birth following both elective and rescue cerclage. MATERIALS AND METHODS: Over a five-year period, we identified 59 women who had a transvaginal cerclage inserted followed by serial cervical length measurement. Of these, 18 were elective cerclages placed at 14 weeks of gestation on the basis of a history of cervical insufficiency and 41 were rescue cerclages performed at gestations ranging from 17 to 23 weeks following a diagnosis of shortened cervix on ultrasound. The women were asymptomatic throughout. RESULTS: There was a strong correlation between cervical length postcerclage and gestation at delivery. For both groups, preterm birth could be predicted by the total cervical length. In the rescue cerclage group, the change in cervical length was predictive, with positive changes associated with later gestation at delivery. The presence of funnelling was predictive of preterm birth in the elective cerclage group only. CONCLUSION: Transvaginal cervical length measurement is useful in the prediction of preterm birth postcerclage placement. Serial cervical length measurement postcerclage may assist with timely addition of interventions such, progesterone and antenatal cortico steroids for fetal lung maturation.