Immunosuppressive therapy of cyclosporin A for severe benzene-induced haematopoietic disorders and a 6-month follow-up

Song, Yuguo; Du, Xuqin; Hao, Fentong; Gu, Xiaoxin; Zhang, Zhenghua; Zhang, Songquan; Li, Chunsheng; Li, Huiling; Ma, Jing

doi:10.1016/j.cbi.2010.03.049

Cited by 14 publications

(6 citation statements)

References 28 publications

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“…They emphasize that many of these subjects responded favorably to removal from continuing benzene exposure along with the use of androgens and immunosuppressive medications. As Irons and associates observed, their few cases with MDS also had excellent long-term survival [6, 54]. …”

Section: Discussionmentioning

confidence: 99%

“…In one report the authors separate 41 such patients as representing either aplastic anemia, pancytopenia ( presumably signifying chronic myelosuppression ), or MDS, with the latter diagnosis only accounting for 4 members of this cohort [54]. They emphasize that many of these subjects responded favorably to removal from continuing benzene exposure along with the use of androgens and immunosuppressive medications.…”

Section: Discussionmentioning

confidence: 99%

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Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

Natelson

Pyatt

2013

Advances in Hematology

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Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by progressive peripheral blood cytopenias associated with ineffective myelopoiesis. They are typically considered neoplasms because of frequent genetic aberrations and patient-limited survival with progression to acute myeloid leukemia (AML) or death related to the consequences of bone marrow failure including infection, hemorrhage, and iron overload. A progression to AML has always been recognized among the myeloproliferative disorders (MPD) but occurs only rarely among those with essential thrombocythemia (ET). Yet, the World Health Organization (WHO) has chosen to apply the designation myeloproliferative neoplasms (MPN), for all MPD but has not similarly recommended that all MDS become the myelodysplastic neoplasms (MDN). This apparent dichotomy may reflect the extremely diverse nature of MDS. Moreover, the term MDS is occasionally inappropriately applied to hematologic disorders associated with acquired morphologic myelodysplastic features which may rather represent potentially reversible hematological responses to immune-mediated factors, nutritional deficiency states, and disordered myelopoietic responses to various pharmaceutical, herbal, or other potentially myelotoxic compounds. We emphasize the clinical settings, and the histopathologic features, of such AMD that should trigger a search for a reversible underlying condition that may be nonneoplastic and not MDS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

Natelson

Pyatt

2013

Advances in Hematology

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“…Epigenetic mechanisms have been implicated in the MDS pathogenesis (40,41), and some studies from China suggest that immune-mediated inflammation is an early developmental step in benzene-induced MDS (34,42,43). Because MDS is prevalent in the elderly, the disease could remain relatively low grade for years and progress to full-blown MDS in conjunction with age-related decreases in immune competency.…”

Section: Discussionmentioning

confidence: 99%

Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis

Schnatter

Glass

Tang

et al. 2012

JNCI Journal of the National Cancer Institute

168

135

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BackgroundBenzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers.MethodsWe updated three nested case–control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose–response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period.ResultsCumulative benzene exposure showed a monotonic dose–response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose–response relationships for AML, CLL, CML, or MPD.ConclusionsRelatively low-level exposure to benzene experienced by petroleum distribution workers was associated with an increased risk of MDS, but not AML, suggesting that MDS may be the more relevant health risk for lower exposures.

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“…This was accompanied by persistent immune‐mediated inflammation and monoclonal or oligoclonal expansion of activated cytotoxic T cell populations . Indicative of an autoimmune process, cases of Bz‐exposed MDS demonstrate positive clinical responses to immunosuppressive therapy and exhibit characteristics essentially identical to those described in evolving MDS with immune features …”

Section: Bz Toxicology In the Modern Eramentioning

confidence: 95%

Cytogenetics in benzene‐associated myelodysplastic syndromes and acute myeloid leukemia: new insights into a disease continuum

Irons

Kerzic²

2014

Annals of the New York Academy of Sciences

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Hematopoiesis in health and disease results from complex interactions between primitive hematopoietic stem cells (HSCs) and the extrinsic influences of other cells in the bone marrow (BM) niche. Advances in stem cell biology, molecular genetics, and computational biology reveal that the immortality, self-renewal, and maintenance of blood homeostasis generally attributed to individual HSCs are functions of the cells' behavior in the normal BM environment. Here we discuss how these advances, together with results of outcomes-based clinical epidemiology studies, provide new insight into the importance of epigenetic events in leukemogenesis. For the chemical benzene (Bz), development of myeloid neoplasms depends predominantly on alterations within the microenvironments in which they arise. The primary persistent disease in Bz myelotoxicity is myelodysplastic syndrome, which precedes cytogenetic injury. Evidence indicates that acute myeloid leukemia arises as a secondary event, subsequent to evolution of the leukemia-initiating cell phenotype within the altered BM microenvironment. Further explorations into the nature of chemical versus de novo disease should consider this mechanism, which is biologically distinct from previous models of clonal cytogenetic injury. Understanding alterations of homeostatic regulation in the BM niche is important for validation of models of leukemogenesis, monitoring at-risk populations, and development of novel treatment and prevention strategies.

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Immunosuppressive therapy of cyclosporin A for severe benzene-induced haematopoietic disorders and a 6-month follow-up

Cited by 14 publications

References 28 publications

Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis

Cytogenetics in benzene‐associated myelodysplastic syndromes and acute myeloid leukemia: new insights into a disease continuum

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