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1.
Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation
Phelan, R., Im, A., Hunter, R. L., Inamoto, Y., Lupo-Stanghellini, M. T., Rovo, A., Badawy, S. M., Burns, L., Eissa, H., Murthy, H. S., et al
Bone marrow transplantation. 2022
Abstract
Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.
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2.
Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation
Phelan, R., Im, A., Hunter, R. L., Inamoto, Y., Lupo-Stanghellini, M. T., Rovo, A., Badawy, S. M., Burns, L., Eissa, H., Murthy, H. S., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. OBJECTIVE Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. STUDY DESIGN We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. RESULTS Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa. CONCLUSION Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.
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3.
Upfront autologous hematopoietic stem cell transplantation consolidation for patients with aggressive B-cell lymphomas in first remission in the rituximab era: A systematic review and meta-analysis
Epperla, N., Hamadani, M., Reljic, T., Kharfan-Dabaja, M. A., Savani, B. N., Kumar, A.
Cancer. 2019
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Abstract
BACKGROUND The outcomes for patients with diffuse large B-cell lymphoma (DLBCL) with adverse clinical prognostic factors such as a high age-adjusted International Prognostic Index (aaIPI) are not optimal. In the current study, the authors performed a systematic review and meta-analysis to assess the totality of evidence pertaining to the efficacy of autologous hematopoietic stem cell transplantation (auto-HCT) consolidation for patients with DLBCL in first remission. METHODS The authors searched the Cochrane and MEDLINE/PubMed databases through December 1, 2018, for studies comparing conventional chemotherapy with rituximab (R-chemo) versus R-chemo and auto-HCT. Two authors independently reviewed all references for study inclusion and extracted data related to benefits (overall survival, progression-free survival, and response rates) and harms (treatment-related mortality and adverse events). RESULTS Four studies (1173 patients) met the inclusion criteria and were included in the current analysis. The median duration of follow-up ranged from 42 to 76 months. There was no difference noted with regard to the overall survival (hazard ratio, 1.01; 95% CI, 0.74-1.37), progression-free survival (hazard ratio, 0.77; 95% CI, 0.58-1.04), or response rates (risk ratio, 0.98; 95% CI, 0.92-1.04) between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone. CONCLUSIONS The findings from what to the authors' knowledge is the first meta-analysis performed in the rituximab era demonstrated no beneficial effect of upfront auto-HCT consolidation in patients with aggressive B-cell non-Hodgkin lymphoma, including high-risk clinical groups (high aaIPI).
PICO Summary
Population
Patients with diffuse large B-cell lymphoma (4 studies, 1173 pts)
Intervention
Chemotherapy with rituximab + autologous stem cell transplantation. (R-chemo and auto-HCT)
Comparison
Chemotherapy with rituximab (R-chemo)
Outcome
There was no difference noted with regard to the overall survival, progression-free survival, or response rates between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone.
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Lower Genital Tract Precancer and Cancer in Hematopoietic Cell Transplant Survivors and the Role of HPV: A Systematic Review and Future Perspectives
Tanweer, M. S., Aljurf, M., Savani, B. N., Iqbal, P. K., Hashmi, S.
Clinical Hematology International. 2019;1(3):142-153
Abstract
Female recipients of hematopoietic cell transplant (HCT) may develop lower genital tract (LGT) dysplasia or new malignancies. A comprehensive systematic review to delineate the occurrence and risk factors for post-HCT LGT precancer and cancer in women was conducted via electronic search of the Cochrane Library, PubMed, Embase, Wiley Online Library, from 1990 to 2018. All studies on the risk, presentation, or incidence of LGT (cervix, vulva, vagina) precancer or cancer post-HCT were included. Reviews, case reports, meta-analysis, book chapters, and studies without the relevant clinical outcomes were excluded. Post-HCT incidence and risk factors for developing LGT precancer or cancer were assessed and determined. Twenty-two out of the original 344 studies met the selection criteria. The risk of LGT cancers in allo-HCT recipients was found to be significantly higher than in the general population, with the standardized incidence ratios of 1.5-48 for cervical cancer and from 19 to 287 for dysplasia. Our review portrays an increased risk of premalignant and malignant neoplasms of female LGT, which have an incompletely described epidemiology and outcomes. Similar to other immunocompromised states, HCT recipients require specific cervical screening guidelines and can greatly benefit from HPV vaccinations. However, there is a lack of prospective data regarding optimum cervical screening in HCT recipients and limited programs offer HPV vaccinations worldwide.
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Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT
Inamoto, Y., Petricek, I., Burns, L., Chhabra, S., DeFilipp, Z., Hematti, P., Rovo, A., Schears, R., Shah, A., Agrawal, V., et al
Bone marrow transplantation. 2018
Abstract
Non-graft-vs.-host disease (non-GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT), but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment, and ocular toxicities associated with medications. We have summarized incidence, risk factors, screening, prevention and treatment of individual complicastions and generated evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical symptoms, signs and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplant physicians and ophthalmologists should be knowledgeable of non-GVHD ocular complications and provide comprehensive collaborative team care.
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Ocular graft-versus-host disease after hematopoietic cell transplantation: Expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT
Inamoto, Y., Valdes-Sanz, N., Ogawa, Y., Alves, M., Berchicci, L., Galvin, J., Greinix, H., Hale, G. A., Horn, B., Kelly, D., et al
Bone marrow transplantation. 2018
Abstract
Ocular graft-versus-host disease (GVHD) occurs in more than half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity, which affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD, regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed in this review. Ocular GVHD has at least three biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have found several novel pathogenic mechanisms, including renin angiotensin system and endoplasmic reticulum stress signaling that can be targeted by therapeutic agents. Many studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. Efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important for all health professionals taking care of HCT recipients to have adequate knowledge of ocular GVHD for optimal care.
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7.
Is there any role for physical therapy in chronic GvHD?
Mohammed, J., Savani, B. N., El-Jawahri, A., Vanderklish, J., Cheville, A. L., Hashmi, S. K.
Bone Marrow Transplantation. 2018;53(1):22-28
Abstract
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.