| 51. |
- Eapen, Mary, et al.
(author)
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Long-Term Survival and Late Deaths after Hematopoietic Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism.
- 2012
-
In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - 1523-6536. ; 18:9
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Journal article (peer-reviewed)abstract
- It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.
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| 52. |
- Eapen, Mathew Suji, et al.
(author)
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Chronic Obstructive Pulmonary Disease and Lung Cancer : Underlying Pathophysiology and New Therapeutic Modalities
- 2018
-
In: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 78:16, s. 1717-1740
-
Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.
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| 53. |
- Marks, David I, et al.
(author)
-
Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission : a comparison with allografts from adult unrelated donors.
- 2014
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 99:2, s. 322-8
-
Journal article (peer-reviewed)abstract
- Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and -DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2-4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.
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| 54. |
- Nicoletti, Paola, et al.
(author)
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Genetic Risk Factors in Drug-Induced Liver Injury Due to Isoniazid-Containing Antituberculosis Drug Regimens
- 2021
-
In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 109:4, s. 1125-1135
-
Journal article (peer-reviewed)abstract
- Drug-induced liver injury (DILI) is a complication of treatment with antituberculosis (TB) drugs, especially in isoniazid (INH)-containing regimens. To investigate genetic risk factors, we performed a genomewide association study (GWAS) involving anti-TB DILI cases (55 Indian and 70 European) and controls (1,199 Indian and 10,397 European). Most cases were treated with a standard anti-TB drug regimen; all received INH. We imputed single nucleotide polymorphism and HLA genotypes and performed trans-ethnic meta-analysis on GWAS and candidate gene genotypes. GWAS found one significant association (rs117491755) in Europeans only. For HLA, HLA-B*52:01 was significant (meta-analysis odds ratio (OR) 2.67, 95% confidence interval (CI) 1.63-4.37, P = 9.4 × 10-5 ). For N-acetyltransferase 2 (NAT2), NAT2*5 frequency was lower in cases (OR 0.69, 95% CI 0.57-0.83, P = 0.01). NAT2*6 and NAT2*7 were more common, with homozygotes for NAT2*6 and/or NAT2*7 enriched among cases (OR 1.89, 95% CI 0.84-4.22, P = 0.004). We conclude HLA genotype makes a small contribution to TB drug-related DILI and that the NAT2 contribution is complex, but consistent with previous reports when differences in the metabolic effect of NAT2*5 compared with those of NAT2*6 and NAT2*7 are considered.
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| 55. |
- Pasquini, Ricardo, et al.
(author)
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HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia: comparison of irradiation and nonirradiation containing conditioning regimens.
- 2008
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In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 14:10, s. 1141-7
-
Journal article (peer-reviewed)abstract
- Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.
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| 56. |
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