Response adaptive salvage treatment with daratumumab-lenalidomide-dexamethasone for newly diagnosed transplant-eligible multiple myeloma patients failing front-line bortezomib-based induction therapy-ALLG MM21.

In Australia, bortezomib-based induction (V-IND) is used in >90% of newly diagnosed transplant-eligible multiple myeloma (MM) patients. Four cycles of V-IND with bortezomib-cyclophosphamide-dexamethasone or bortezomib-lenalidomide-dexamethasone are available via the Pharmaceutical Benefits Scheme prior to autologous stem cell transplantation (ASCT). Patients who demonstrate suboptimal response or who are refractory to V-IND demonstrate inferior survival, representing a subgroup of MM where an unmet need persists. We evaluated an early, response-adapted approach in these patients by switching to an intensive sequential therapeutic strategy incorporating daratumumab-lenalidomide-dexamethasone-based (DRd) salvage, high-dose melphalan ASCT followed by DRd consolidation and R maintenance. The overall response rate following four cycles of DRd salvage was 72% (95% credible interval: 57.9-82.4); prespecified, dual, Bayesian proof-of-concept criteria were met. Euro-flow minimal residual disease (MRD) negativity was 46% in the intention-to-treat population and 79% in the evaluable population following 12 cycles of DRd consolidation. At the 24-month follow-up, median progression-free survival and overall survival were not reached. DRd salvage was well tolerated with grade 3 and 4 events reported in 24% and 8% respectively. Response-adapted DRd combined with ASCT achieves high rates of MRD negativity and durable disease control in this functional high-risk group.

Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma.

High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 108/kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (

Variation in inspiratory time and tidal volume with T-piece neonatal resuscitator: association with operator experience and distraction.

The most recent Neonatal Resuscitation Programme (NRP 5th edition) guidelines recognise the T-piece resuscitator (Neopuff) device as an acceptable method of administering a pre-selected peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP). While these are constant, other parameters are operator-dependent. Although in widespread clinical use, there is little published data on the use of the T-piece resuscitator in neonatal resuscitation. This study showed that despite fixed inflating pressures, less experienced operators used prolonged inspiratory times. Wide variation in mean airway pressure and tidal volume were seen in all operators.

Thoracic CT scanning in critically ill patients. Information obtained frequently alters management.

Conventional radiographic studies of the chest in the intensive care unit often fail to positively identify suspected intrathoracic pathology due to many patient- and equipment-related variables. Our experience has indicated that CT scanning of the chest improves diagnostic accuracy, precisely defines anatomic abnormalities, frequently affects treatment decisions, and has been performed safely in this fragile patient population. Examples of correctable lesions have included pneumothorax, empyema, lung abscess, mediastinal abscess and pleural effusion. Chest CT findings always occurred while the portable plane chest radiographs were nondiagnostic. CT-directed intervention often improved patient outcome.

Correlation between needle biopsy of lung tumors and histopathologic analysis of resected specimens.

Needle aspiration of a pulmonary mass may accurately delineate malignant from nonmalignant pulmonary lesions; however, needle aspiration may be unable to identify a specific cell type. Therefore, a retrospective review of patients undergoing needle aspiration of pulmonary masses was carried out for the years, 1979 through September 1984. A Lee needle was used, which produces a sample of tissue 1-mm in diameter suitable for histopathologic analysis as well as a cytologic specimen. A total of 87 needle biopsies were carried out, but only 46 patients later underwent resection. Five patients (6 percent) sustained a pneumothorax, and four required a chest tube. Minimal hemoptysis occurred in three patients (3 percent). Eight patients were subsequently found to have benign lesions, and there were 38 malignant tumors. Seven needle biopsies (18 percent; 7/38) were nondiagnostic and subsequently proved to be malignant. Thirty-one needle biopsies were diagnostic of malignant neoplasms (82 percent; 31/38). Twenty specimens showed the same cell type as the needle biopsy (65 percent 20/31). Eleven resected specimens disagreed with the cell type from the needle biopsy (35 percent; 11/31). In these 11 patients a change in management was indicated because of the delineation of a different cell type in only four (11 percent of all 38 patients with cancer). Mixed tumors and small cell carcinoma provide the area of most concern. Our conclusions are that needle biopsy accurately indicated a malignant neoplasm in 82 percent of the patients undergoing later resection and that the specimens from Lee needle biopsy accurately predicted the cell type in 65 percent of the specimens. The inaccurate histologic diagnosis was important clinically in only 11 percent of the patients. Overall, the needle biopsy of pulmonary lesions provided a correct decision on management in 87 percent of the cases in which biopsy provided diagnosis of a malignant neoplasm (31 patients).

Readmission of patients to the surgical intensive care unit: patient profiles and possibilities for prevention.

Because experience is lacking regarding the profile of patients readmitted to a surgical ICU (SICU), we retrospectively reviewed total admissions, readmissions, patient profiles, and characteristics of illness requiring readmission to a multidisciplinary SICU. During a 1-yr period, the 721 recorded admissions included 68 readmissions for 57 patients (9.4% of the total). Eight patients had multiple readmissions. Seventy-five percent of the original admissions in these 57 patients occurred postoperatively, 9% were due to trauma, and 16% were caused by nonsurgical illness. Mortality for readmitted patients was 26%. Although 53 (78%) discharges were deemed appropriate, 62% of the patients manifested one or more of a retrospectively selected group of warning signs which might have alerted the responsible physician to alter the treatment plan. In half of these patients the reason for readmission was related to the warning sign. Readmission was related to the original disease in 65% of the incidents, while a new patient problem initiated readmission in 38%. The most common new problems were cardiopulmonary insufficiency and infection. All but one patient readmitted with pulmonary problems displayed retrospective evidence of clear warning signs before the original discharge. Recognition of SICU readmission patterns will allow more precise discharge planning: to delay discharge, to effect a lateral transfer, or to initiate a stepdown unit which may be able to help prevent costly and potentially lethal patient outcomes.