Elderly patients with multiple myeloma: Towards a frailty approach?

Purpose of review To describe how to better identify frail multiple myeloma patients and to treat them appropriately. Recent findings Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly improved the outcome of multiple myeloma patients in the last decade. However, both in clinical trials and in daily clinical practice, elderly multiple myeloma patients have shown lesser benefit. This is mainly due to less stringent use of proteasome inhibitors and IMiDs, increased toxicity, and subsequent early discontinuation of therapy in elderly. Summary Multiple myeloma typically affects elderly patients. Approximately one-Third of patients are older than 75 years at diagnosis. Moreover, at least 30% are frail, both due to disease-related symptoms and (agerelated) decline in physical capacity, presence of comorbidities, frailty, polypharmacy, nutritional status, and cognitive impairment. Treatment regimens that are investigated in clinical trials for transplant-ineligible patients have largely been investigated in fit, rather than frail patients, the latter being typically excluded or highly underrepresented therein. Data on the feasibility and efficacy of current standards of care are therefore lacking in frail patients. Preliminary data suggest a higher toxicity and discontinuation rate, loss of efficacy, and impaired quality of life in frail patients. Geriatric assessment helps to identify frail patients according to their functional and cognitive status. Both the International Myeloma Working Group (IMWG)-frailty index and Revised Myeloma Comorbidity Index constitute recently proposed algorithms that easily identify intermediate-fit and frail patients. Ongoing and future clinical trials, specifically designed for frail patients, will hopefully define frailty-directed treatment selection

Intensive Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation During a 10-Year Period in 64 Patients with Germ Cell Tumor

AbstractDespite gratifying cure rates in germ cell tumors, conventional-dose chemotherapy achieves long-term remissions in less than 50% of patients at high risk. High-dose chemotherapy followed by autologous (auto) peripheral blood stem cell transplantation (PBSCT) has shown impressive remission rates in high-risk and relapsed germ cell tumors. We report on 64 consecutive patients with high- (n = 39), intermediate- (n = 18), and refractory or relapsed low- (n = 7) risk germ cell tumors who underwent auto-PBSCT between January 1993 and February 2003. PBSCTs were performed as a single (n = 40) or repeated (n = 24) transplantation using either etoposide, ifosfamide, and carboplatin (n = 80) or related protocols (paclitaxel, ifosfamide, carboplatin, etoposide [n = 7]; carboplatin, etoposide, thiotepa [n = 4]). With a median follow-up of 6 years, estimated 2- and 5-year overall survivals were 77.2% (95% confidence interval [CI] 66.7-87.7) and 73.1% (95% CI 61.7-84.5), respectively. We observed unfavorable results in those patients showing refractoriness to cisplatin (hazard ratio 20.36; 95% CI 6.64-62.47) or no response to induction chemotherapy (hazard ratio 10.67; 95% CI 1.37-83.37). Auto-PBSCT was well tolerated, showed objective antitumor activity, and achieved long-term survival in patients at high risk and with relapse. Our data suggest that auto-PBSCT can increase response rates and may improve the outcome in these patients

Marrow versus Blood-Derived Stem Cell Grafts for Allogeneic Transplantation from Unrelated Donors in Patients with Active Myeloid Leukemia or Myelodysplasia

Peripheral blood stem cells (PBSCs) are increasingly used as the graft source in allogeneic hematopoietic cell transplantation. We compared long-term outcome after unrelated donor transplantation of 85 consecutive patients with acute myelogenous leukemia or myelodysplastic syndrome regarding disease status (early disease [CR1, refractory anemia); n = 25 and advanced/active disease [>CR1, >refractory anemia]; n = 60) who were treated with conventional conditioning regimens followed by bone marrow (BM) or PBSC grafts. Graft-versus-host disease prophylaxis consisted mainly of cyclosporine A, short-course methotrexate, and anti-T-lymphocyte globulin. After a median follow-up of 118 months (68-174), the 10-year event-free survival rate after peripheral blood stem cell transplantation (PBSCT) was 54.8% (95% confidence interval [CI], 39.7%-69.8%), and after bone marrow transplantation (BMT), it was 27.9% (14.5%-41.3%; P < .004). In the advanced/active disease group, the 10-year event-free survival rate after PBSCT was 50% (30.8%-69.2%), and after BMT, it was 23.5% (9.3%-37.8%; P < .007). Non relapse mortality was less after PBSCT than BMT (14.3% vs 30.2%), respectively. In multivariate Cox regression analysis, PBSCT showed a better overall survival (OS; hazard ratio [HR], 0.43; 95% CI, 0.23-0.79; P = .007) compared to BMT; unfavorable/unknown prognostic impact cytogenetic abnormalities were an adverse factor for all patients (HR, 2.202; 95% CI, 1.19-4.06; P = .011). In patients with advanced disease, the use of PBSCs showed a significant favorable outcome via multivariate analysis (HR, 0.49; 95% CI, 0.24-0.99; P = .046). Outcome of acute myelogenous leukemia/myelodysplastic syndrome after unrelated hematopoietic cell transplantation is adversely affected by cytogenetic abnormalities and state of remission at hematopoietic cell transplantation. PBSC as a graft source has a significant favorable influence on survival

Accidental Hypothermia in a Swiss Alpine Trauma Centre-Not an Alpine Problem.

BACKGROUND Research in accidental hypothermia focuses on trauma patients, patients exposed to cold environments or patients after drowning but rarely on hypothermia in combination with intoxications or on medical or neurological issues. The aim of this retrospective single-centre cohort study was to define the aetiologies, severity and relative incidences of accidental hypothermia, methods of measuring temperature and in-hospital mortality. METHODS The study included patients ≥18 years with a documented body temperature ≤35 °C who were admitted to the emergency department (ED) of the University Hospital in Bern between 2000 and 2019. RESULTS 439 cases were included, corresponding to 0.32 per 1000 ED visits. Median age was 55 years (IQR 39-70). A total of 167 patients (38.0%) were female. Furthermore, 63.3% of the patients suffered from mild, 24.8% from moderate and 11.9% from severe hypothermia. Exposure as a single cause for accidental hypothermia accounted for 12 cases. The majority were combinations of hypothermia with trauma (32.6%), medical conditions (34.2%), neurological conditions (5.2%), intoxications (20.3%) or drowning (12.0%). Overall mortality was 22.3% and depended on the underlying causes, severity of hypothermia, age and sex