Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation

Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days; P <.0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days; P =.03). Donor RBC chimerism was delayed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while neither event occurred in 12 patients following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P =.008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.     

The effect of training and diet on lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats

Treadmill training for 1 hr/day for 10 wk did not significantly affect chylomicron, very low density, low density, or high density lipoprotein cholesterol in rats fed either a high carbohydrate (glucose) or high fat (coconut oil) diet. Lipoprotein lipase activity of heart, adipose tissue, and skeletal muscle fibers was also unaffected by training. Carbohydrate feeding, however, when compared to fat feeding significantly lowered all lipoprotein cholesterol values as well as heart and fast-oxidative-glycolytic muscle fiber lipase activity and, conversely, significantly elevated hepatic triglyceride lipase activity. Thus, in the rat, an alteration in the serum lipid profile did not occur as a result of training, but dietary differences did independently influence serum lipid levels and tissue enzyme activity. It is suggested that human studies need to control for the possible independent influence of dietary differences when investigating the effects of training on lipoprotein metabolism.     

Different dietary fatty acids are associated with blood lipids in healthy South African men and women: The PURE study

Background

Preliminary data from the baseline Prospective Urban Rural Epidemiology (PURE) study in South Africa indicated a higher prevalence of dyslipidemia than previous South African studies. The intake of specific individual dietary fatty acids may affect blood lipids differently than sub-groups of fat (i.e. polyunsaturated fatty acids). We investigated the dietary intake of different individual fatty acids and their associations with blood lipids, in relation to urbanization and gender.

Methods

Cross-sectional data analysis within the PURE baseline study of healthy subjects (n = 1950, 35–70 years) from rural and urban areas. Dietary data were collected and blood lipid analysis performed.

Results

Intake of individual fatty acids was significantly higher in urban than rural dwellers. However, the intake of n-3 PUFAs was below recommendations in all groups. Total cholesterol and LDL were higher in females than in males, with no rural?urban differences. Intake of alpha-linolenic acid (ALA) was positively associated with total cholesterol (β = 0.143) and triglycerides (β = 0.256) in males. The risk for having elevated LDL also increased with increased intake of ALA (OR 1.49, 95% CI 1.04, 2.14) in males. In females, arachidonic acid and eicosapentaenoic acid (EPA) were positively associated with total cholesterol and arachidonic acid was also positively associated with LDL, whereas docosahexaenoic acid was negatively associated with total cholesterol and LDL.

Conclusions

These results suggest that specific individual dietary fatty acids may affect blood lipids in males differently than in females irrespective of rural or urban dwelling. The positive association between ALA and total cholesterol and triglycerides in males is a concern, because current advice aims to improve the dietary linoleic acid to ALA ratio by increasing ALA intake.     

Phase I/II multisite trial of optimally dosed clofarabine and low-dose TBI for hematopoietic cell transplantation in acute myeloid leukemia

Clofarabine is an immunosuppressive purine nucleoside analog that may have better anti-leukemic activity than fludarabine. We performed a prospective phase I/II multisite trial of clofarabine with 2 Gy total body irradiation as non-myeloablative conditioning for allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia who were unfit for more intense regimens. Our main objective was to improve the 6-month relapse rate following non-myeloablative conditioning, while maintaining historic rates of non-relapse mortality (NRM) and engraftment. Forty-four patients, 53 to 74 (median: 69) years, were treated with clofarabine at 150 to 250 mg/m², of whom 36 were treated at the maximum protocol-specified dose. One patient developed multifactorial acute kidney injury and another developed multiorgan failure, but no other grade 3 to 5 non-hematologic toxicities were observed. All patients fully engrafted. The 6-month relapse rate was 16% (95% CI, 5%-27%) among all patients and 14% (95% CI, 3%-26%) among high-risk patients treated at the maximum dose, meeting the pre-specified primary efficacy endpoint. Overall survival was 55% (95% CI, 40%-70%) and leukemia-free survival was 52% (95% CI, 37%-67%) at 2 years. Compared to a historical high-risk cohort treated with the combination of fludarabine at 90 mg/m² and 2 Gy TBI, protocol patients treated with the clofarabine-TBI regimen had lower rates of overall mortality (HR of 0.50, 95% CI, 0.28-0.91), disease progression or death (HR 0.48, 95% CI, 0.27-0.85), and morphologic relapse (HR 0.30, 95% CI, 0.13-0.69), and comparable NRM (HR 0.85, 95% CI 0.36-2.00). The combination of clofarabine with TBI warrants further investigation in patients with high-risk AML.     

Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study

Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.     

Vulvar anatomy and labia minoraplasty

Aim of video/Introduction

Female genital cosmetic surgery is performed for aesthetic reasons as well as for medical and functional indications, such as congenital labia minora hypertrophy. The purpose of this video is to teach vulvar anatomy and review labia minorplasty techniques.

Methods

We demonstrate one technique in this video.

Conclusions

There are a variety of different techniques for labia minorplasty. When deciding the most appropriate technique to use, the patient’s goals must be considered.     

Effect of shellfish consumption on cholesterol absorption in normolipidemic men

Noncholesterol marine sterols, abundant in molluscan shellfish, could inhibit cholesterol absorption. Eight normolipidemic males were fed for 3 weeks each three natural food diets in which a mixture of oysters and clams, crab, or chicken was served as the primary source of animal protein. The diets were equalized for caloric distribution, cholesterol, and n-3 fatty acids, leaving the noncholesterol marine sterols in the oyster/clam diet (444 mg/2,000 kcal) as the potential lipid-modifying variable. Cholesterol absorption was measured by plasma isotope ratio after doses of oral 14C- and intravenously infused 3H-labeled cholesterol. Cholesterol absorption was lower (42 +/- 4%) during the oyster/clam diet than during the chicken (54 +/- 3%, P less than 0.01) or crab (55 +/- 3%, P less than 0.01) diet periods. There was no difference between the chicken and crab diet periods. Total plasma cholesterol and triglycerides, very low density lipoprotein cholesterol and triglycerides, and low density and high density lipoprotein (HDL) cholesterol were not significantly different between any of the diets. The ratio of the HDL2-/HDL3-cholesterol was higher following the oyster/clam diet (0.46 +/- 0.09) than the chicken diet (0.32 +/- 0.06, P less than 0.05). Plasma and red cell membrane n-3 fatty acids were not significantly different among the three diets, but red cell membrane n-3 fatty acids increased as a function of time regardless of dietary sequence.