Anemia and leukopenia following intravenous colloidal silver infusions-Clinical and hematological features, unique peripheral blood film appearance and effective therapy with supplemental oral copper and apheresis.

Alternative medical therapy with multiple intravenous colloidal silver infusions may cause severe illness, including profound copper deficiency-induced anemia and hepatic toxicity. No chelating agent for silver poisoning exists and effective therapy requires apheresis in combination with continuous administration of oral copper.

Does occupational exposure to formaldehyde cause hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells?

Several cross-sectional studies of a single population of workers exposed to formaldehyde at one of two factories using or producing formaldehyde-melamine resins in China have concluded that formaldehyde exposure induces damage to hematopoietic cells that originate in the bone marrow. Moreover, the investigators interpret observed differences between groups as evidence that formaldehyde induces myeloid leukemias, although the mechanisms for inducing these diseases are not obvious and recently published scientific findings do not support causation. Our objective was to evaluate hematological parameters and aneuploidy in relation to quantitative exposure measures of formaldehyde. We obtained the study data for the original study (Zhang et al. 2010 ) and performed linear regression analyses. Results showed that differences in white blood cell, granulocyte, platelet, and red blood cell counts are not exposure dependent. Among formaldehyde-exposed workers, no association was observed between individual average formaldehyde exposure estimates and frequency of aneuploidy, suggested by the original study authors to be indicators of myeloid leukemia risk.

Acquired myelodysplasia or myelodysplastic syndrome: clearing the fog.

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.

Extreme thrombocytosis and cardiovascular surgery: risks and management.

Extreme thrombocytosis is a major risk factor for excessive bleeding and for thrombosis, either of which can complicate cardiovascular surgical and interventional procedures. Extreme thrombocytosis can also cause an unusual syndrome, erythromelalgia, that results in a type of chronic microvascular occlusive arterial disease. We present the differential diagnosis of conditions that may lead to extreme thrombocytosis, 3 cases (each of which illustrates a different potential complication), and a review of the pertinent medical literature. Correcting excessive thrombocytosis is typically not difficult, whether electively or acutely, and effective therapy usually controls thrombosis and excessive hemorrhage post-procedurally.

Temozolomide-induced myelodysplasia.

A patient who had received temozolomide (TMZ) as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS). TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT) for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML) is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

Benzene exposure and refractory sideroblastic erythropoiesis: is there an association?

The myelodysplastic syndromes (MDS) consist of a group of diverse hematological disorders that carry an increased risk of transforming into acute myeloid leukemia. They may appear de novo and without obvious cause (primary or de novo MDS) or be induced by certain mutagenic environmental or therapeutic toxins (secondary MDS). Excessive exposures to benzene are generally considered to be a potential environmental risk factor for both MDS and acute myeloid leukemia. However, such risk is unproven for each disease component within the MDS classification. A critical review of the refractory sideroblastic disorders strongly suggests that benzene exposure is not a potential cause of this distinct and still-evolving subset of MDS. The widely disparate nature of MDS suggests that epidemiologic studies can only provide meaningful data on associations and potential causation of its component syndromes by a disease-specific analysis, as is currently advocated for other hematological malignancies.

Benzene-induced acute myeloid leukemia: a clinician's perspective.

Benzene-induced acute myeloid leukemia (AML) is considered a secondary form of AML, based both in theory and on limited cohort observations. Its latency, cytogenetic aberrations, and clinical features are thought similar to, or identical with, AML resulting from the use of modern day cytotoxic agents for chemotherapy and immunotherapy. Although distinction between secondary AML and the far more common de novo AML is difficult to establish with certainty in any given case, latency from toxic therapeutic and environmental exposure and certain clinical and pathological features generally separate these two entities. AML is the only human neoplasm proven to be potentially caused by benzene, which actually is an obsolete form of chemotherapy. Despite many years of environmental regulation, alleged toxic exposure to this ubiquitous chemical has become an expanding area of litigation. A review of benzene-induced AML suggests that, in developed countries, this entity should no longer merit serious consideration among workers in the modern petrochemical industry and related fields.

Pregnancy-induced pancytopenia with cellular bone marrow: distinctive hematologic features.

Three patients with pregnancy-induced pancytopenia also exhibited variable features of sideroblastic anemia and amegakaryocytic thrombocytopenia. Treatment with anti-thymocyte globulin proved highly effective in two cases and a spontaneous remission occurred in the third. This illness is distinct from the more commonly reported incidental association of pregnancy with classic aplastic anemia. Its differentiation from myelodysplasia is also emphasized.

Myelodysplasia with isolated trisomy 15: a 15-year follow-up without specific therapy.

A 41-year-old patient manifested pancytopenia with macrocytosis following pesticide exposure. She was later found to have myelodysplasia with trisomy 15. Over a 15-year period of observation, and with no specific therapy, her hematological disorder remains stable, despite persistence of the chromosomal aberration. This and similar reported observations suggest that the course of this uncommon form of myelodysplasia is often indolent and not accurately predicted by application of the widely used International Prognostic Scoring System for the myelodysplastic syndromes.