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Summary: Immunomodulatory drugs (IMiDs) have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic backbone at all phases of therapy. Although well‐tolerated, IMiDs increase rates of venous thromboembolism (VTE). In this phase IV, single‐arm pilot study, fifty patients with MM on IMiDs received apixaban 2·5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for six months. The primary safety outcomes were rates of major haemorrhage and clinically relevant non‐major haemorrhage over six months. The primary efficacy outcome was the rate of symptomatic VTE over six months. IMiDs used were lenalidomide (58%) or pomalidomide (42%). During the six‐month evaluation period, no patients experienced major haemorrhage or VTE. Three patients experienced clinically relevant, non‐major haemorrhage which was managed medically, and all were able to resume apixaban. One patient stopped therapy shortly after initiation due to an allergic reaction to apixaban. No patients experienced stroke, myocardial infarction, or death. In this pilot study, low‐dose apixaban was safe and well‐tolerated as a primary prevention therapy of VTE for patients with MM receiving IMiDs. Further studies are needed to validate low‐dose apixaban as a standard primary prevention anti‐thrombotic strategy for patients with MM receiving IMiDs. [ABSTRACT FROM AUTHOR]

Objective: To describe upper dermal microvasculature of healthy human skin in terms of density and size of cutaneous blood vessels, leukocyte velocity, and leukocyte interactions with the endothelium. Methods: We used a reflectance confocal microscope, the VivaScope 1500, to acquire videos of individual cell motion. Results: We found no rolling leukocytes in the upper microvasculature of ten healthy subjects. We observed "paused" leukocytes, that is, leukocytes that temporarily stop, coinciding with the simultaneous stopping of the rest of the blood flow. We imaged more paused (median: 1.0 per subject) and adherent (1.5) leukocytes in the forearm than in the chest (median 0 paused and 0 adherent per subject) per 5 minutes of videos per body site. Leukocytes were paused for a median of 7 seconds in the forearm and 3 seconds in the chest, and we found no correlation between this parameter and the blood vessel or leukocyte size. We visualized blood flow change direction. Flowing leukocyte velocities followed a lognormal distribution and were on average higher in the chest (117 µm/s) than in the forearm (66 µm/s). Conclusion: The proposed method and reported values in healthy skin provide new insights into intact human skin microcirculation. [ABSTRACT FROM AUTHOR]

Background: Haploidentical bone marrow transplant (haplo‐BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo‐BMT for SCD. Methods: A multi‐institution learning collaborative was developed in the context of a phase II clinical trial of a non‐myeloablative, related haplo‐BMT with post‐transplant cyclophosphamide for SCD. We report results from a cohort of 23 patients for whom immune reconstitution data up to one year were available. Results: Median age was 14.8 years. Out of 23, 18 participants received pre‐conditioning with azathioprine, hydroxyurea, and hypertransfusions. 70% (16/23) of participants had multiple indications for haplo‐BMT. We observed excellent immune reconstitution of CD4, CD8, CD19, and CD56 cellular subsets by 6 months post transplant. Engraftment rate and event‐free survival in this cohort were 100% and 96%, respectively. 70% (16/23) of patients had at least one viral reactivation or infection, including CMV 35% (8/23), HHV‐6 22% (5/23), and polyoma virus 17% (4/23), with no cases of post‐transplant lymphoproliferative disease. Conclusion: Further prospective studies are needed to better characterize immune reconstitution and the immunologic basis for increased viral reactivation following haplo‐BMT with post‐transplant cyclophosphamide for SCD. [ABSTRACT FROM AUTHOR]

Background: Estimating the extent of affected skin is an important unmet clinical need both for research and practical management in many diseases. In particular, cutaneous burden of chronic graft‐vs‐host disease (cGVHD) is a primary outcome in many trials. Despite advances in artificial intelligence and 3D photography, progress toward reliable automated techniques is hindered by limited expert time to delineate cGVHD patient images. Crowdsourcing may have potential to provide the requisite expert‐level data. Materials and methods: Forty‐one three‐dimensional photographs of three cutaneous cGVHD patients were delineated by a board‐certified dermatologist. 410 two‐dimensional projections of the raw photos were each annotated by seven crowd workers, whose consensus performance was compared to the expert. Results: The consensus delineation by four of seven crowd workers achieved the highest agreement with the expert, measured by a median Dice index of 0.7551 across all 410 images, outperforming even the best worker from the crowd (Dice index 0.7216). For their internal agreement, crowd workers achieved a median Fleiss's kappa of 0.4140 across the images. The time a worker spent marking an image had only weak correlation with the surface area marked, and very low correlation with accuracy. Percent of pixels selected by the consensus exhibited good correlation (Pearson R = 0.81) with the patient's affected surface area. Conclusion: Crowdsourcing may be an efficient method for obtaining demarcations of affected skin, on par with expert performance. Crowdsourced data generally agreed with the current clinical standard of percent body surface area to assess cGVHD severity in the skin. [ABSTRACT FROM AUTHOR]

Background: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT).Methods: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes.Results: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P = .04; relative risk, 1.60 [95% CI, 1.15-2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P = .20).Conclusions: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors. Cancer 2016;122:3005-3014. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT. [ABSTRACT FROM AUTHOR]

Objective To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. Methods In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Results Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician- and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of hypomethylating agent 5-azacitidine in treating patients with acute leukemia. The authors claim that low doses of 5-azacitidine may maximize the graft-versus-leukemia effect and may be tolerated well after allogeneic transplantation (HSCT). They add that it may induce durable remissions for patients who develop disease recurrence after HSCT.