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This year’s most interesting hematology stories
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As usual, at the end of each year, Joe Bertino, MD, and I, with the assistance of our other Section Editors, choose to emphasize some of HemOnc Today’s recently published articles. This column presents some comments about five nonmalignant hematology contributions.
Controversies about the use of erythropoietic-stimulating agents continue to rile our subspecialty. Many of us worry about “babies being thrown out with the bath water” through federal mandates (gleefully extended by insurance companies) that restrict reimbursement for these valuable pharmaceuticals. We extensively reviewed these troublesome issues in April, wherein several guest commentators weighed in. All agreed that the CSA’s decision not to reimburse Medicare patients for prescribed ESAs — unless hemoglobin levels fall to below 10 — is a travesty. This decision was made despite the FDA’s admission that no data implicate any deleterious effects in patients treated to hemoglobin levels of 12. Can one seriously doubt that quality of life is significantly better in patients with hemoglobin levels of 12 rather than 9.9? Yet despite concerted American Society of Hematology and ASCO representations to federal agencies, as well as to Congress, Medicare patients suffering chemotherapy-associated anemia remain unable to secure reimbursement for ESA treatment.
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In a related area, in August we reviewed the critical role that IV iron can play in patients treated with ESAs — that is by producing much more reliable hemoglobin elevations. Michael Auerbach, MD, has championed this concept and reviewed several recent papers validating the assertion. The fear that IV iron may provoke anaphylactic reactions is no longer much of an issue because low–molecular-weight iron dextrans and newer iron saccharides have replaced older and more dangerous high–molecular-weight dextran products. Transfusion requirements have markedly declined among dialysis patients treated with combined IV iron and ESAs. I believe our marrow-failure patients should now also be provided the benefit of this combination.
Romiplostim
Another marrow-stimulating pharmaceutical, romiplostim (AMG531; NPlate, Amgen), has engendered significant excitement this year. As noted in our August issue, this synthetic Fc-peptide fusion protein (peptibody) stimulates thrombopoiesis and has been approved for use in patients with chronic idiopathic thrombocytopenic purpura. Initial beneficial results presented at last year’s ASH meeting have held up and now are being extended to trials in other thrombocytopenic situations. Several papers in this arena were given at ASH this month and at least one will demonstrate real benefit in patients with myelodysplasia undergoing azacitidine (Vidaza, Pharmion) therapy. Moreover, development of immune blockade of the drug’s effects — as was the case with previous thrombopoietins — evidently has not been a problem to date. I suspect we will soon see trials of this drug with many other chemotherapy-requiring disorders. I fervently hope that hemorrhagic catastrophes will be reliably reduced in our chemotherapy-treated patients when supplemented with this and analogous pharmaceuticals presently in the pipeline.
Hydroxyurea
In March, we reviewed conclusions from an NIH-sponsored conclave of experts in sickle diseases that particularly examined the role (and troubling underuse) of hydroxyurea in “sicklers.” As noted in an August editorial written by Russell E. Ware, PhD, and Peter E. Newburger, MD, although hydroxyurea offers an inexpensive and remarkably effective ameliorative therapy for patients with sickle cell disease, probably less than 50% of hematologists prescribe it, and perhaps as few as 30% of adult sicklers are currently so-treated. The drug has been studied in sickle cell diseases for more than 25 years and has proven to benefit patients without significant long-term toxicity — including neoplasia development. However, the possibility of later fertility problems in children treated with the drug remains a concern. The document produced by the NIH conference should be read by all hematologists. One hopes that it will encourage a significant increase in hydroxyurea use for this miserable and common disorder.
Anticoagulants
Two articles concerning anticoagulants are worth emphasizing. In February, Kenneth Bauer, MD, editorialized on a new oral anti-Factor Xa agent, rivaroxaban (Xarelto, Bayer/Ortho-McNeil). That it soon may replace parenteral anticoagulants in acute situations, as well as warfarin in more chronic conditions seems likely. As reported at last year’s ASH meeting, the drug was studied in two separate trials with more than 5,000 patients undergoing hip or knee replacement surgeries. Participants were provided either subcutaneous enoxaparin (Lovenox, Sanofi Aventis) or the new oral, anti-Factor Xa compound, rivaroxaban. In both trials the oral agent actually decreased DVT, pulmonary embolization and death by 50% to 80% when compared with heparin and did so with no increased bleeding risk. It seems likely that rivaroxaban soon will be approved, perhaps causing heparin-associated thrombocytopenia to disappear from our lexicon (much to the annoyance of malpractice lawyers). In March, we expanded our reporting in this arena — describing a new oral antithrombin agent, dabigatran (Pradaxa, Boehringer-Ingelheim). Again, in postoperative joint-replacement patients, this drug was equally effective to enoxaparin in preventing postoperative thromboembolic events with a similar safety profile. A large trial comparing it with warfarin (Coumadin, Bristol Myers Squibb) in patients with atrial fibrillation is ongoing. Its efficacy and safety, if found equivalent or better than warfarin, will spell the demise of international normalized ratio-assaying labs and will improve quality of life in patients requiring lifetime anticoagulation. It should be noted that the promising results with dabigatran have, so far, not been associated with the reversible hepatic toxicity that (probably irrationally) sunk its cousin compound, ximelagatran (Exanta, AstraZeneca).
Procoagulants
Turning 180ºF to procoagulants, in May, we noted a new FDA approval of a convenient, easily-stored coagulation Factor VIIa recombinant for use in catastrophically bleeding patients. NovoSeven RT (Novo Nordisk) can be stored for as long as three years at temperatures of 36ºF to 45ºF. It likely will be used in patients (even in developing countries) with life-threatening bleeding, especially in those with cerebral hemorrhage. Of interest in this regard, results that were to be reported at this year’s ASH meeting demonstrated that small amounts of recombinant Factor VIIa can significantly benefit patients with central nervous system bleeding when added to prothrombin complex concentrate (PCC) — for instance, when provided to patients taking warfarin who are suffering cerebral bleeds. This combination allows one to forego infusion of fresh frozen plasma — a dicey therapy in elderly patients who may be unable to tolerate large fluid loads. This combination seems rational, because PCC itself is relatively deficient in Factor VII.