Hematologic masquerade of rhabdomyosarcoma

We present the case of a 12-year-old boy admitted with the diagnosis of acute leukemia, but found to have an infiltration of the marrow by an alveolar rhabdomyosarcoma (RMS) as determined by the cytogenetic demonstration of a t(2;13)(q25;q14). A primary tumor could not be found. With this case as a basis, we have tabulated features of all similar cases in the literature and discuss the possible optimal approaches to establishing the correct diagnosis in such patients.     

Catheter-delivered ultrasound therapy for native coronary arterial thrombosis and occluded saphenous vein grafts

Acute coronary thrombosis, overlying ruptured atherosclerotic plaque, is the hallmark of myocardial infarction and unstable angina. Despite use of modern therapeutic modalities, including glycoprotein IIb/IIIa antagonists and stenting, intracoronary thrombus heralds an increased risk of serious complications following percutaneous coronary interventions (PCI). Abundant in vitro and in vivo experimental data have proven that ultrasound energy is capable of lysing intravascular thrombus without injuring the vessel wall. Expanding experience and technological advancements now allow us to use this tool in clinical practice. In this article we review the emergence of percutaneous ultrasonic thrombolysis as a safe and effective tool for treatment of patients in various clinical settings associated with coronary thrombosis.     

Issues in the assessment of the safety and efficacy of tenecteplase (TNK-tPA)

While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.     

Not the presence but the amount of clonal DNA detectable in remission of acute myeloid leukemia is predictive for relapse

Abstract: Objectives: The persistence of clonal cells after chemotherapy, or a re‐emerging of clonal cells in remission (CR) or at relapse in patients with acute myeloid leukemia (AML) was studied to assess the prognostic significance of the amount of clonal DNA in predicting the clinical outcome. Methods: Clonal rearrangements in the gene sequences of retinoic acid receptor (RAR) α, major breakpoint cluster region (M‐bcr), immunoglobulin (Ig)‐JH, T‐cell receptor (TcR) β, myeloid lymphoid leukemia or cytokines (GM‐CSF, G‐CSF, IL‐3) detected in bone marrow samples from 37 patients with primary AML (pAML) or secondary AML (sAML) were investigated. A relative increase or decrease of clonal DNA in the course of AML was evaluated by comparing the optical densities of DNA bands of the rearranged genes and the total amount of DNA. Results: High amounts of clonal DNA were detectable at diagnosis, during persisting disease and at relapse (Ø 39%, 35%, or 38% of total DNA, respectively), compared to 20% in complete remission (CR). Amounts of clonal DNA (except for Ig‐JH gene rearrangements) were of prognostic significance at diagnosis, patients with less than 33% clonal DNA were characterized by significantly longer relapse‐free survival times (all cases: p = 0.01; pAML: p = 0.002). Patients in CR exhibiting less than 5% (all cases) or 15% (pAML) clonal DNA showed longer relapse‐free survival times (p = 0.08 or p = 0.03, respectively). Vice versa, significantly higher amounts of clonal DNA (all cases 51% vs. pAML 54%) could be detected in cases studied at diagnosis who relapsed in the following 5 months (all cases p = 0.01) or 14 months (pAML p = 0.007). Significantly higher amounts of clonal DNA (33%) could be detected in cases studied in CR who relapsed in the following 4 months (all cases p = 0.002 or pAML p = 0.006, respectively). Moreover, we could prove disease progression on a cellular level months before the clinical onset of sAML after a period of MDS. Conclusions: Clonal, gene‐rearranged DNA is regularly detectable at diagnosis and during persisting AML, in CR and at relapse. However, the presence, rather than the amount of clonal DNA detectable in CR is predictive for relapse. These data might indicate the significance of gene rearrangement analyses in the course of AML to identify cases with a high risk of relapse, independently from the karyotype.     

A phase II trial of pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), a novel anti-fibrosing agent, in myelofibrosis with myeloid metaplasia

The anti-fibrotic and cytokine modulatory properties of pirfenidone suggest its usefulness in the treatment of myelofibrosis with myeloid metaplasia (MMM). In a prospective study, 28 patients with MMM were treated with oral pirfenidone. Twelve patients completed 1 year of therapy; 13 were withdrawn because of disease progression and three because of drug intolerance. Only one patient experienced a clinically relevant benefit with respect to anaemia and splenomegaly. The overall lack of clinical benefit correlated with no significant improvement in the bone marrow morphological features of the disease. We conclude that pirfenidone has no significant clinical or biological activity in MMM.     

Adult T-Cell Leukemia Associated with Gastric Carcinoma: Report of a Case

A 67-year-old man was admitted to our hospital with nausea and epigastralgia, and a diagnosis of smoldering type adult T-cell leukemia (ATL) associated with advanced gastric carcinoma was made. The gastric carcinoma had caused pyloric stenosis, and investigations revealed regional lymph node metastasis. The patient underwent total gastrectomy, splenectomy, cholecystectomy, and lymph node dissection with a Roux-en-Y anastomosis. Histological examination of the regional lymph nodes revealed not only metastases of gastric carcinoma, but also of ATL lymphoma, indicating a final diagnosis of advanced gastric carcinoma with locoregional lymph node due to both metastasis of the gastric carcinoma and the ATL lymphoma. Despite the administration of postoperative adjuvant chemotherapy comprised of cisplatin/adriamycin/5-fluorouracil in combination with oral etoposide and immunotherapy using ubenimex, paraplegia suddenly developed caused by the metastasis of ATL to the epidural space. Resection of this metastatic tumor for decompression of the spinal cord resulted in resolution of the paraplegia; however, the patient died about 1 month later from rapid systemic tumor growth. Received: November 8, 1999 / Accepted: September 26, 2000