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Meeting the needs of CML patients in resource-poor countries.
Malhotra, H, Radich, J, Garcia-Gonzalez, P
Hematology. American Society of Hematology. Education Program. 2019;(1):433-442
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Abstract
Subsequent to the development and global availability of BCR/ABL-targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various publications in LMICs vs developed countries. These include differences in incidence and prevalence rates, age and stage of disease at diagnosis, response rates, and survival. Some of the possible reasons proposed for these are varying socioeconomic milieu (impacting availability of effective drugs and essential monitoring), environmental factors (mainly exposure to viral infections and pesticides), nutritional factors with interplay of malnutrition and diet on drug absorption and blood levels, and possible unknown genetic factors. Although generic first-generation TKIs (imatinib) are available in many parts of the world, several challenges remain in providing optimal treatment to patients with CML in resource-poor countries. Some of these include availability of optimal and high-quality BCR/ABL testing, availability and expense related to use of second- and third-generation TKIs (nilotinib, dasatinib, bosutinib, and ponatinib) and hematopoietic stem cell transplantation, issues with compliance and toxicities of drugs, and ensuring a minimal standard-of-care treatment and monitoring for every patient diagnosed with CML. For the purpose of this article, the more objective country label-LMIC-coined by the World Bank will be used (gross national income per capita between $1026 and $3995; World Bank, June 2019). Some of these issues will be discussed in this article in greater detail by experts in the field in 3 different but interconnected sections.
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Non-Graft-versus-Host Disease Ocular Complications after Hematopoietic Cell Transplantation: Expert Review from 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 for Blood and Marrow Transplantation.
Inamoto, Y, Petriček, I, Burns, L, Chhabra, S, DeFilipp, Z, Hematti, P, Rovó, A, Schears, R, Shah, A, Agrawal, V, et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019;(5):e145-e154
Abstract
Non-graft-versus-host disease (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 transplantation 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 summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate 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 signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.
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Treatment of MDS.
Platzbecker, U
Blood. 2019;(10):1096-1107
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Abstract
The heterogeneous nature of myelodysplastic syndromes (MDS) demands a complex and personalized variety of therapeutic approaches. Among them, allogeneic hematopoietic stem cell transplantation remains the only potentially curative option and is accessible to only a small number of fit patients. For the majority of patients with MDS, treatment strategies are nonintensive and risk-adapted (by the revised version of the International Prognostic Scoring System), ranging from iron chelation and growth factors to lenalidomide and hypomethylating agents. These approaches are noncurative and aimed instead at improving cytopenias and quality of life and delaying disease progression. These limitations underpin the need for more translational research-based clinical trials in well-defined subgroups of patients with MDS. Indeed, much progress has been made over the past decade in understanding the complex molecular mechanisms underlying MDS. Unfortunately, this has not yet translated into approval of novel treatment options. There is a particularly urgent medical need in patients failing current first-line therapies, such as with erythropoiesis-stimulating or hypomethylating agents. Nevertheless, actual developments are expected to pave the way for exciting novel therapeutic opportunities. This review provides an overview of the current therapeutic landscape in MDS focusing on recent advances in clinical and translational research.
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Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation.
Mourad, N, Michel, RP, Marcus, VA
Archives of pathology & laboratory medicine. 2019;(9):1131-1143
Abstract
CONTEXT.—: Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications. OBJECTIVE.—: To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil-induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome. DATA SOURCES.—: The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences. CONCLUSIONS.—: The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.
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Echinocandin prophylaxis in patients undergoing haematopoietic cell transplantation and other treatments for haematological malignancies.
Epstein, DJ, Seo, SK, Brown, JM, Papanicolaou, GA
The Journal of antimicrobial chemotherapy. 2018;(suppl_1):i60-i72
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Abstract
Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well. Although currently approved echinocandins require daily intravenous administration, the drugs have a favourable safety profile and more predictable pharmacokinetics than mould-active azoles. Clinical data support the efficacy and safety of echinocandins for antifungal prophylaxis in haematology and HCT patients, though data are less robust than for azoles. Notably, sparse evidence exists supporting the use of echinocandins as antifungal prophylaxis for patients with significant graft-versus-host disease (GvHD) after HCT. Two drugs that target (1,3)-β-d-glucan are in development, including an oral glucan synthase inhibitor and an echinocandin with unique pharmacokinetics permitting subcutaneous and weekly administration. Echinocandins are a reasonable alternative to azoles and other agents for antifungal prophylaxis in patients undergoing intensive chemotherapy for haematological malignancy or those receiving HCT, excluding those with significant GvHD.
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Hematopoietic Stem Cell Transplantation for Adult Philadelphia-Negative Acute Lymphoblastic Leukemia in the First Complete Remission in the Era of Minimal Residual Disease.
Bourlon, C, Lacayo-Leñero, D, Inclán-Alarcón, SI, Demichelis-Gómez, R
Current oncology reports. 2018;(4):36
Abstract
PURPOSE OF REVIEW The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph-) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD). RECENT FINDINGS Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been found to correlate directly with the risk of relapse. Currently, the clinical challenge consists on applying MRD and molecular failure to integrate novel agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft versus leukemia (GVL) effect after transplant.
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Optimization of nutrition during allogeneic hematologic stem cell transplantation.
Baumgartner, A, Hoskin, K, Schuetz, P
Current opinion in clinical nutrition and metabolic care. 2018;(3):152-158
Abstract
PURPOSE OF REVIEW Malnutrition before and during hematopoietic stem cell transplantation (HSCT) is an independent risk factor for mortality in patients undergoing hematopoietic stem cell transplantation. Yet, optimal use of nutritional support to improve outcomes remains controversial. Our aim was to do an up-to-date literature review regarding nutritional therapy in allogeneic HSCT, the neutropenic diet and the use of immunonutrients. RECENT FINDINGS Several observational studies find malnutrition to be associated with poor outcome, increased complications and lower overall survival. There are, however, few interventional trials proving the benefits of nutritional therapy in this population compared with no nutritional treatment. Regarding routes of treatment, studies suggested that parenteral nutrition is associated with higher risk for complications compared with enteral nutrition. Whether the use of specific formulas, such as immunonutrition, has a beneficial effect on clinical outcome is not established yet. Strict use of neutropenic diets did not show a reduction in infection risk and clinical outcome, and can no longer be recommended. SUMMARY Our updated search confirms that malnutrition is a strong negative predictor for outcome, yet optimal use of nutritional interventions to prevent or treat malnutrition remains ill-defined. There is need for larger randomized trials to better address these issues in the future.
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Type 2 Diabetes Mellitus, the Metabolic Syndrome, and Its Components in Adult Survivors of Acute Lymphoblastic Leukemia and Hematopoietic Stem Cell Transplantations.
Bielorai, B, Pinhas-Hamiel, O
Current diabetes reports. 2018;(6):32
Abstract
PURPOSE OF REVIEW A growing number of pediatric acute lymphoblastic leukemia (ALL) and hematopoietic stem cell transplantation (HSCT) survivors reach adulthood and face long-term health-related problems. We review risk factors and the prevalence of the metabolic syndrome (MetS), a cluster of obesity-related comorbidities, including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, impaired glucose metabolism, and type 2 diabetes in ALL and HSCT survivors. RECENT FINDINGS Components of the MetS are already detected during the first year of ALL maintenance therapy and significantly worsen over time. The prevalence of MetS increases at a faster rate in this setting than in the general population. Factors found to be of the greatest potential risk to the development of the MetS are central obesity, increased BMI, irradiation therapy, older age, poor diet, and low level of physical activity. The early onset of MetS and its components among ALL and HSCT survivors calls for early and continuous screening to identify those at risk and to implement preventive measures.
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ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients.
Cesaro, S, Dalianis, T, Hanssen Rinaldo, C, Koskenvuo, M, Pegoraro, A, Einsele, H, Cordonnier, C, Hirsch, HH, ,
The Journal of antimicrobial chemotherapy. 2018;(1):12-21
Abstract
OBJECTIVES To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. METHODS Review of English literature and evidence-based recommendations by expert consensus. RESULTS BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. CONCLUSIONS BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials.
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Transplantation in patients with iron overload: is there a place for magnetic resonance imaging? : Transplantation in iron overload.
Mavrogeni, S, Kolovou, G, Bigalke, B, Rigopoulos, A, Noutsias, M, Adamopoulos, S
Heart failure reviews. 2018;(2):173-180
Abstract
In iron overload diseases (thalassemia, sickle cell, and myelodysplastic syndrome), iron is deposited in all internal organs, leading to functional abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only treatment offering a potential cure in these diseases. Our aim was to describe the experience in the field and the role of magnetic resonance imaging in the evaluation of iron overload before and after HSCT. Magnetic resonance imaging (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver iron overload and guide tailored treatment. Currently, HSCT offers complete cure in thalassemia major, after overcoming the immunologic barrier, and should be considered for all patients who have a suitable donor. The overall thalassemia-free survival of low-risk, HLA-matched sibling stem cell transplantation patients is 85-90%, with a 95% overall survival. The problems of rejection and engraftment are improving with the use of adequate immunosuppression. However, a detailed iron assessment of both heart and liver is necessary for pre- and post-transplant evaluation. In iron overload diseases, heart and liver iron evaluation is indispensable not only for the patients' survival, but also for evaluation before and after HSCT.