Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials.

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem cell mobilization yields, apheresis attempts, and engraftment outcomes for patients from each study. Adult transplantation-eligible patients with NDMM received induction therapy consisting of daratumumab plus carfilzomib/lenalidomide/dexamethasone (D-KRd) for four 28-day cycles in the single-arm MASTER trial or lenalidomide/bortezomib/dexamethasone (RVd) with or without daratumumab (D) for four 21-day cycles in the randomized GRIFFIN trial, followed by stem cell mobilization and ASCT in both studies. Institutional practice differed regarding plerixafor use for stem cell mobilization; the strategies were upfront (ie, planned plerixafor use) or rescue (ie, plerixafor use only after mobilization parameters indicated failure with granulocyte colony-stimulating factor [G-CSF] alone). Descriptive analyses were used to summarize patient characteristics, stem cell mobilization yields, and engraftment outcomes. In MASTER, 116 D-KRd recipients underwent stem cell mobilization and collection at a median of 24 days after completing induction therapy. In GRIFFIN, 175 patients (D-RVd, n = 95; RVd, n = 80) underwent mobilization at a median of 27 days after completing D-RVd induction therapy and 24 days after completing RVd induction therapy. Among those who underwent mobilization and collection, 7% (8 of 116) of D-KRd recipients, 2% (2 of 95) of D-RVd recipients, and 6% (5 of 80) of RVd recipients did not meet the center-specific minimally required CD34+ cell yield in the first mobilization attempt; however, nearly all collected sufficient stem cells for ASCT on remobilization. Among patients who underwent mobilization, plerixafor use, either upfront or as a rescue strategy, was higher in patients receiving D-KRd (97%; 112 of 116) and D-RVd (72%; 68 of 95) compared with those receiving RVd (55%; 44 of 80). The median total CD34+ cell collection was 6.0 × 106/kg (range, 2.2 to 13.9 × 106/kg) after D-KRd induction, 8.3 × 106/kg (range, 2.6 to 33.0 × 106/kg) after D-RVd induction, and 9.4 × 106/kg (range, 4.1 to 28.7 × 106/kg) after RVd induction; the median days for collection were 2, 2, and 1, respectively. Among patients who underwent mobilization, 98% (114 of 116) of D-KRd patients, 99% (94 of 95) of D-RVd patients, and 98% (78 of 80) of RVd patients underwent ASCT using median CD34+ cell doses of 3.2 × 106/kg, 4.2 × 106/kg, and 4.8 × 106/kg, respectively. The median time to neutrophil recovery was 12 days in all 3 treatment groups across the 2 trials. Because both trials used different criteria to define platelet recovery, data on platelet engraftment using the same criteria are not available. Four cycles of daratumumab- and lenalidomide-based quadruplet induction therapy had a minimal impact on stem cell mobilization and allowed predictable stem cell harvesting and engraftment in all patients who underwent ASCT. Upfront plerixafor strategy may be considered, but many patients were successfully collected with the use of G-CSF alone or rescue plerixafor.

Risk of Cytomegalovirus Infection with Post-Transplantation Cyclophosphamide in Haploidentical and HLA-Matched Unrelated Donor Transplantation.

Post-transplantation cyclophosphamide (PTCy) is effective for graft-versus-host disease (GVHD) prevention but is associated with an increased risk of cytomegalovirus (CMV) infection. The effect of PTCy on CMV infection in matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) is unclear, and whether there is any difference in CMV risk with 1 or 2 doses of PTCy is not well established. This study aimed to compare the incidence of CMV infection and the association between T cell recovery in patients who received PTCy-based GVHD prophylaxis and those who received non-PTCy-based GVHD prophylaxis. We conducted a retrospective study to compare the risk of CMV infection in 3 cohorts: cohort A (n = 94), matched related donor (MRD)/MUD HSCT with calcineurin inhibitor-based GVHD prophylaxis; cohort B (n = 103), MRD/MUD HSCT with 1 dose of PTCy, tacrolimus, and mycophenolate mofetil (MMF); and cohort C (n = 28), haploidentical donor HSCT with 2 doses of PTCy, tacrolimus, and MMF. The day +100 cumulative incidence of CMV infection was 29% for cohort A, 39% for cohort B, and 61% for cohort C (P = .009), with no difference among the cohorts in the duration of viremia (P = .46). CD3+ and CD4+ T cell counts were significantly higher in cohort A at day +30 but not at days +60 and +90. Nonrelapse mortality (NRM) trended higher and relapse was significantly lower with PTCy. There was no difference in survival among the 3 cohorts. There is an increased risk of early CMV infection in patients receiving PTCy irrespective of donor type and number of PTCy doses compared with those not receiving PTCy. Strategies focusing on CMV prevention in PTCy recipients to mitigate the risk of NRM may lead to improved long-term outcomes.

A systematic scoping review of clinical indications for induction of labour.

BACKGROUND: The proportion of women undergoing induction of labour (IOL) has risen in recent decades, with significant variation within countries and between hospitals. The aim of this study was to review research supporting indications for IOL and determine which indications are supported by evidence and where knowledge gaps exist. METHODS: A systematic scoping review of quantitative studies of common indications for IOL. For each indication, we included systematic reviews/meta-analyses, randomised controlled trials (RCTs), cohort studies and case control studies that compared maternal and neonatal outcomes for different modes or timing of birth. Studies were identified via the databases PubMed, Maternity and Infant Care, CINAHL, EMBASE, and ClinicalTrials.gov from between April 2008 and November 2019, and also from reference lists of included studies. We identified 2554 abstracts and reviewed 300 full text articles. The quality of included studies was assessed using the RoB 2.0, the ROBINS-I and the ROBIN tool. RESULTS: 68 studies were included which related to post-term pregnancy (15), hypertension/pre-eclampsia (15), diabetes (9), prelabour rupture of membranes (5), twin pregnancy (5), suspected fetal compromise (4), maternal elevated body mass index (BMI) (4), intrahepatic cholestasis of pregnancy (3), suspected macrosomia (3), fetal gastroschisis (2), maternal age (2), and maternal cardiac disease (1). Available evidence supports IOL for women with post-term pregnancy, although the evidence is weak regarding the timing (41 versus 42 weeks), and for women with hypertension/preeclampsia in terms of improved maternal outcomes. For women with preterm premature rupture of membranes (24-37 weeks), high-quality evidence supports expectant management rather than IOL/early birth. Evidence is weakly supportive for IOL in women with term rupture of membranes. For all other indications, there were conflicting findings and/or insufficient power to provide definitive evidence. CONCLUSIONS: While for some indications, IOL is clearly recommended, a number of common indications for IOL do not have strong supporting evidence. Overall, few RCTs have evaluated the various indications for IOL. For conditions where clinical equipoise regarding timing of birth may still exist, such as suspected macrosomia and elevated BMI, researchers and funding agencies should prioritise studies of sufficient power that can provide quality evidence to guide care in these situations.

Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications.

Filgrastim (FIL) is the most common growth factor combined with plerixafor for autologous hematopoietic progenitor cell mobilization, but requires daily, multi-injection administration. We adopted a standardized mobilization regimen with pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of 235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in peripheral blood on first day of collection was 48 and median collection yield was 7.27 × 106 CD34+ cells/kg (range, 0.32 to 39.6 × 106 CD34+ cells/kg) after a mean of 1.6 apheresis collections. Overall, 83% of patients achieved the mobilization target, and 95% reached the minimum necessary CD34+ cell yield to proceed with transplantation (2 × 106 CD34+ cells/kg). Because FIL is weight-based and dosed daily, the cost comparison with PEG is influenced by patient weight and number of apheresis sessions required. A cost simulation using actual patient data indicates that PEG is associated with lower cost than FIL for the majority of patients. Autologous hematopoietic progenitor cell mobilization with PEG and plerixafor is practical, effective, and not associated with increased cost compared with FIL mobilization.

Introducing sensitive issues and self-care strategies to first year midwifery students.

OBJECTIVE: first year midwifery students learn early in semester about situations in midwifery where a high level of emotion is expressed, such as taking a sexual history, being faced with the body image changes of pregnancy and working with women in the extreme pain of labour. Commencing students usually have not had exposure to the realities of studying and working in midwifery, and often have an idealised view of midwifery that may lead to attrition from the course. We aimed to equip students with personal and professional tools to discuss sensitive issues in midwifery and promote self-care through the development of two workshops. The first workshop focussed on sensitive issues in midwifery and the second on self-care strategies. DESIGN: quantitative and qualitative data were collected pre and post workshops using a survey. SETTING: the workshops were developed at one university in New South Wales, Australia. PARTICIPANTS: Beginning first year midwifery students MEASUREMENTS: feeling more comfortable, confident and knowledgeable was measured using a paired t-test from the responses on a pre and post workshop survey. Content analysis was performed on the qualitative survey responses. FINDINGS: there were significant increases in the students feeling more comfortable to discuss sensitive issues in midwifery following the first workshop. They found meeting new people, respecting opinions, normalizing confronting topics to be valuable and useful. The second workshop found significant differences in being more confident and knowledgeable to access and try new self-care strategies in both their personal and professional life. Students discussed learning to be more mindful in order to prepare for stressful situations. They became aware of their feeling and thoughts when under stress and said they would practice techniques including meditation. CONCLUSION: the workshops assisted the students to develop peer support, self-care strategies and coping mechanisms when faced with the intimate and sometimes confronting nature of midwifery practice. Through embedding these first year workshops early in the degree we hope to address attrition rates and facilitate the students' to become the compassionate, caring, woman-centred midwives that they envisioned. IMPLICATIONS FOR PRACTICE: the workshops have the potential for replication in other universities to support and nurture beginning midwifery students.

'Stress, anger, fear and injustice': An international qualitative survey of women's experiences planning a vaginal breech birth.

OBJECTIVE: the outcomes of the Term Breech Trial had a profound impact on women's options for breech birth, with caesarean section now seen as the default method for managing breech birth by many clinicians. Despite this, the demand for planned vaginal breech birth from women does exist. This study aimed to examine the experiences of women who sought a vaginal breech birth to increase understanding as to how to care for women seeking this birth option. DESIGN: an electronic survey was distributed to women online via social media. The survey consisted of qualitative and quantitative questions, with the qualitative data being the focus of this paper. Open ended questions sought information on the ways in which woman sourced a clinician skilled in vaginal breech birth and the level of support and quality of information provided from clinicians regarding vaginal breech birth. Thematic analysis was used to analyse and code the qualitative data into major themes. FINDINGS: in total, 204 women from over seven countries responded to the survey. Written responses to the open ended questions were categorised into seven themes: Seeking the chance to try for a VBB; Encountering coercion and fear; Putting the birth before the baby?; Dealing with emotional wounds; Searching for information and support; Traveling across boundaries; Overcoming obstacles in the system. KEY CONCLUSIONS: for women seeking vaginal breech birth, limited system and clinical support can impede access to balanced information and options for care. Recognition of existing evidence on the safety of vaginal breech birth, as well as the presence of clinical guidelines that support it, may assist in promoting vaginal breech birth as a legitimate option that should be available to women.

Supporting Women Planning a Vaginal Breech Birth: An International Survey.

OBJECTIVE: The aim of this study was to explore the experiences of women who planned a vaginal breech birth. METHOD: An online survey was developed consisting of questions regarding women's experiences surrounding planned vaginal breech birth. The survey was distributed between April 2014 and January 2015 to closed membership Facebook groups that had a consumer focus on vaginal breech birth. RESULTS: In total, 204 unique responses to the survey were obtained from women who had sought the option of a vaginal breech birth in a previous pregnancy. Most women (80.8%) stated that they were happy with the birth choices they made, and a significant proportion (89.4%) would attempt a vaginal breech birth in subsequent pregnancies. Less than half of women were formally referred to a clinician skilled in vaginal breech birth when their baby was diagnosed breech (41.8%), while the remainder sourced a clinician themselves. Half of the women felt supported by their care provider (56.7%) and less than half (42.3%) felt supported by family and friends. CONCLUSION: The women who responded to this international survey sought the option of a vaginal breech birth, were subsequently happy with this decision, and would attempt a vaginal breech birth in their next pregnancy. Access to vaginal breech birth is important for some women; however, this choice may be challenging to achieve. Consistent information and support from clinicians is important to assist decision-making.

Women's experiences of planning a vaginal breech birth in Australia.

BACKGROUND: In many countries, planned vaginal breech birth (VBB) is a rare event. After the Term Breech Trial in 2000, VBB reduced and caesarean section for breech presentation increased. Despite this, women still request VBB. The objective of this study was to explore the experiences and decision-making processes of women who had sought a VBB. METHODS: A qualitative study using descriptive exploratory design was undertaken. Twenty-two (n = 22) women who planned a VBB, regardless of eventual mode of birth were recruited. The women had given birth at one of two maternity hospitals in Australia that supported VBB. In-depth, semi-structured interviews using an interview guide were conducted. Interviews were analysed thematically. RESULTS: Twenty two women were interviewed; three quarters were primiparous (n = 16; 73%). Nine (41%) were already attending a hospital that supported VBB with the remaining women moving hospitals. All women actively sought a vaginal breech birth because the baby remained breech after an external cephalic version - 12 had a vaginal birth (55%) and 10 (45%) a caesarean section after labour commenced. There were four main themes: Reacting to a loss of choice and control, Wanting information that was trustworthy, Fighting the system and seeking support for VBB and The importance of 'having a go' at VBB. CONCLUSIONS: Women seeking a VBB value clear, consistent and relevant information in deciding about mode of birth. Women desire autonomy to choose vaginal breech birth and to be supported in their choice with high quality care.