Evaluation of Eltrombopag in Thrombocytopenia Post Hematopoietic Cell Transplantation: Rertrospective Observational Trial.

BACKGROUND: Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet transfusion is the maintain stay of treatment. Eltrombopag is approved for the treatment of thrombocytopenia associated with different diseases, however; data on eltrombopag treatment post HCT are limited. METHODS: This is a retrospective cohort study evaluating the effect of eltrombopag on platelet recovery in patients with persistent thrombocytopenia post HCT. The primary endpoint was platelet recovery to ≥ 20,000/µL for 7 consecutive days without transfusion support after starting eltrombopag. Secondary endpoint was platelet recovery to ≥ 50,000/µL for 7 consecutive days. RESULTS: Twenty-one patients were included. Twelve (75%) of 16 patients became independent from platelet transfusions. Median time from starting eltrombopag to last transfusion was 60 days (range, 9-226 days). Ten (63%) of 16 transfusion dependent patients with platelet count < 20,000/µL achieved the primary endpoint. Seven (33%) patients of 21 included had successful platelet recovery (ie, ≥50,000/µL without transfusion support) and the median time to platelet recovery in patients who achieved it was 32 days (range, 13-265 days). Ten patients (48%) were able to successfully discontinue eltrombopag without recurrence of thrombocytopenia. CONCLUSION: Our findings demonstrated that eltrombopag appears to have a clinically significant impact on platelet recovery in persistent thrombocytopenic patients post HCT.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (Part II): Clinical, technical and socio-economic considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.

Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.

BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.

Is there any role for physical therapy in chronic GvHD?

Chronic GvHD is the leading cause of non-relapse mortality in recipients of hematopoietic cell transplantation. Although the benefit of physical therapy (PT) has been reported in some GvHD studies, a literature gap is identified in demonstrating the exact role of different types of PT interventions and their impact on GvHD outcomes. An electronic search was undertaken using 13 peer-reviewed databases from 1994 to 2016. JADAD scoring method was used to score the quality of articles. PT interventions utilized for non-GvHD aspects of transplantation were excluded. Out of the 4775 articles on the electronic search, 297 articles were reviewed out of which 3 fulfilled the selection criteria. Moderately high evidence for effectiveness of supervised PT intervention was found, whereas moderate evidence for a self-administered exercise program was established. No safety concerns with PT were observed in any of the studies, however none of the studies were conducted to directly evaluate safety and effectiveness specifically in GvHD patients. PT is a safe but understudied therapy for GvHD. Limited evidence on the effectiveness of most PT interventions is available through randomized control trials. Well-designed trials are urgently needed for musculoskeletal GvHD especially with focused PT interventions.

Childhood to adult transition and long-term follow-up after blood and marrow transplantation.

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (BMT) is on the increase worldwide. With BMT's increasing utilization and increasing success, the number of BMT survivors in the United States alone is expected to surpass 500 000 by the year 2030. BMT survivors are susceptible to a host of long-term side effects and complications. The pediatric and adolescent and young adult (AYA) populations comprise an increasing proportion of BMT survivors. Though these populations are both at risk of a specific set of sequelae and faced with the additional challenge of transitioning to adult care, no previous literature has addressed their specific challenges. In this review, we illustrate with clinical vignettes the need for focused and specific survivorship clinics for pediatric/AYA BMT survivors. We then focus on the following areas pertaining to pediatric BMT survivorship and care: (1) psychological health, (2) neurocognition, (3) endocrine health, (4) infertility resources, (5) issues in transition from pediatric to adult clinicians, (6) preventative services and (7) cost of care issues.

Voriconazole exposure and the risk of cutaneous squamous cell carcinoma in allogeneic hematopoietic stem cell transplant patients.

BACKGROUND: Voriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo-HSCT. METHODS: We retrospectively reviewed consecutive adult patients who underwent allo-HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time-dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use. RESULTS: In our cohort of 381 allo-HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post-voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5 years post allo-transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180 days of use, P < 0.001). CONCLUSION: This is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal use in this patient population.

Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype-phenotype correlation.

Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.

Consanguinity among the risk factors for underweight in children under five: a study from rural Sindh.

BACKGROUND: Malnutrition is a common problem, especially in developing countries. Of the 11 million children under 5 who die each year in the developing countries mainly from preventable causes, the death of about 54% are either directly or indirectly attributable to malnutrition. The objectives of this study were to assess the prevalence and associated factors for underweight in rural Sindh. METHODS: A cross-sectional survey was conducted in Jhangara Town, located in District Dadu, Sindh. Eight hundred children under 5 years of age were enrolled. A questionnaire was used to elicit required information and anthropometric measurements were made. RESULTS: The overall prevalence for underweight was 54.3% in the study population, which was higher than the prevalence reported by PDHS 1990-91. In multivariate analysis, various factors for underweight were consanguinity (OR = 1.5, 95% CI = 1.08-2.07), low birth weight (parents' perspective) (OR = 1.6, 95% CI = 1.08-2.16) and lack of breast-feeding (OR = 2.7, 95% CI = 1.19-6.17). CONCLUSION: Effective strategies to discourage consanguineous marriages between first cousins are required. Promoting breast feeding is another factor that should be incorporated while designing control strategies to reduce morbidity and mortality due to malnutrition in children (< 5 years).