Daratumumab during Myeloma Induction Therapy Is Associated with Impaired Stem Cell Mobilization and Prolonged Post-Transplant Hematologic Recovery.

Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.

Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML.

INTRODUCTION: Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT) in first remission (CR1). Clonal hematopoiesis of indeterminate potential (CH) increases the risk for hematological and cardiovascular disorders and death. The impact of CH persisting after ASCT in AML patients is unclear. MATERIALS AND METHODS: We retrospectively investigated the prognostic value of persisting DNMT3A, TET2, or ASXL1 (DTA) mutations after ASCT. Patients underwent stratification depending on the presence of DTA mutations. RESULTS: We investigated 110 consecutive AML patients receiving ASCT in CR1 after two induction cycles at our center between 2007 and 2020. CH-related mutations were present in 31 patients (28.2%) after ASCT. The baseline characteristics were similar between patients with or without persisting DTA mutations after ASCT. The median progression free survival was 26.9 months in patients without DTA mutations and 16.7 months in patients with DTA mutations (HR 0.75 (0.42-1.33), p = 0.287), and the median overall survival was 80.9 and 54.4 months (HR 0.79 (0.41-1.51), p = 0.440), respectively. CONCLUSION: We suggest that DTA-CH after ASCT is not associated with an increased risk of relapse or death. The persistence of DTA mutations after induction should not prevent AML patients in CR1 from ASCT consolidation. Independent studies should confirm these data.

Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08).

BACKGROUND: Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. PATIENTS AND METHODS: An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. RESULTS: Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. CONCLUSION: Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.

Treatment pathways and quality improvement for patients with acute myocardial infarction at a tertiary care center.

The timely diagnosis and treatment of acute ST-segment elevation myocardial infarction (STEMI) have become paramount to improving outcomes in this population. Many states, including North Carolina, have established systems to guide regional emergency providers in caring for STEMI. We describe the current pathway for diagnosis and treatment of STEMI for providers referring patients to Duke University Hospital, including a system for expedited patient transport and activation of the cardiac catheterization laboratory from a wide referral base. There is also a structured process for review of cases and quality improvement, which incorporates physicians, administrators, and emergency medical personnel.

Monotoring adherence to prescribed medication in type 2 diabetic patients treated with sulfonylureas.

BACKGROUND: Data on adherence to prescribed medication amongst diabetics are scarce. The purpose of this study was to collect information about the dynamics and patterns of compliance of elderly patients with type 2 diabetes mellitus on oral treatment by using different assessment techniques. METHODS: Adherence to prescribed sulfonylurea medication was prospectively assessed by Self-report (Sr), Pill count (Pc) and using a Medication Event Monitoring System (MEMS) over a period of 2 months in 19 elderly patients with type 2 diabetes mellitus. A pressure-activated microprocessor allowing the registration of each opening is located in the cap of the MEMS drug container. MEMS dosage adherence (MEMSd) was defined as the number of bottle openings divided by the number of doses prescribed), and MEMS regimen adherence (MEMSr) was defined as the percentage of days in which the dose regimen was taken as prescribed. RESULTS: Adherence rates were 96.8 +/- 19.6% for Pc, 92.6 +/- 19.9% for MEMSd and 78.6 +/- 28.3% for MEMSr. Adherence rates for Pc were 103.8 +/- 10.9% in once daily regimens and 87.3 +/- 25.2% in bid/tid regimens (p = 0.0686). MEMSd was 101.0 +/- 4.8% in once daily regimens versus 81.0% +/- 26.8% in bid/tid regimens (p = 0.0255). MEMSr was 93.6 +/- 5.7% in once daily regimens versus only 57.8 +/- 34.1% in bid/tid regimens (p = 0.0031). Assessed by MEMSd as many as 42.1% of the participants had adherence rates greater than 100%. Over-compliance was found primarily in once daily regimens. CONCLUSION: Adherence rates varied with different assessment techniques. Adherence rates were far from optimal. Once daily dosage led to significantly better adherence rates than two or three times daily regimens. However, over-compliance was surprisingly high and occurred more frequently on a once daily regimen.