PubMed HealthSearch

PubMed · 8618472

Interpreting data in AML.

Abstract

Steady progress has been made in the treatment of acute myeloid leukemia since the discovery of daunorubicin in the 1960s. Advances in new drug activity have contributed greatly to that and are responsible for curing about 20 percent of patients diagnosed today. Progress in supportive care has been equally important; broad-spectrum antibiotics are now allowing patients to survive long enough to receive an adequate course of chemotherapy, to which most patients respond with a complete remission. More recently, the development of colony-stimulating factors and their safe use during induction therapy in high-risk patients has allowed greater numbers of patients to be adequately treated during the initial phase of therapy. The most significant recent advance in treatment for acute leukemia is the demonstration that certain leukemic syndromes respond dramatically to specific interventions that are substantially less active in other leukemic syndromes. The challenge for the near future is to understand the mechanisms behind these empiric observations and, for the long-term, to learn to use such information to design molecularly targeted therapy for specific leukemic syndromes that are characterized by unique molecular features. Antisense oligonucleotide therapeutic research is one first step in that direction.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P H Wiernik. 1996. Interpreting data in AML.. https://pubmed.ncbi.nlm.nih.gov/8618472/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators.

BACKGROUND: Recent controlled trials suggest that thrombolytic therapy may be an effective initial treatment for acute arterial occlusion of the legs. A major potential benefit of initial thrombolytic therapy is that limb ischemia can be managed with less invasive interventions. METHODS: In this randomized, multicenter trial conducted at 113 North American and European sites, we compared vascular surgery (e.g., thrombectomy or bypass surgery) with thrombolysis by catheter-directed intraarterial recombinant urokinase; all patients (272 per group) had had acute arterial obstruction of the legs for 14 days or less. Infusions were limited to a period of 48 hours (mean [+/-SE], 24.4+/-0.86), after which lesions were corrected by surgery or angioplasty if needed. The primary end point was the amputation-free survival rate at six months. RESULTS: Final angiograms, which were available for 246 patients treated with urokinase, revealed recanalization in 196 (79.7 percent) and complete dissolution of thrombus in 167 (67.9 percent). Both treatment groups had similar significant improvements in mean ankle-brachial blood-pressure index. Amputation-free survival rates in the urokinase group were 71.8 percent at six months and 65.0 percent at one year, as compared with respective rates of 74.8 percent and 69.9 percent in the surgery group; the 95 percent confidence intervals for the differences were -10.5 to 4.5 percentage points at six months (P=0.43) and -12.9 to 3.1 percentage points at one year (P=0.23). At six months the surgery group had undergone 551 open operative procedures (excluding amputations), as compared with 315 in the thrombolysis group. Major hemorrhage occurred in 32 patients in the urokinase group (12.5 percent) as compared with 14 patients in the surgery group (5.5 percent) (P= 0.005). There were four episodes of intracranial hemorrhage in the urokinase group (1.6 percent), one of which was fatal. By contrast, there were no episodes of intracranial hemorrhage in the surgery group. CONCLUSIONS: Despite its association with a higher frequency of hemorrhagic complications, intraarterial infusion of urokinase reduced the need for open surgical procedures, with no significantly increased risk of amputation or death.

Acute Disease

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens.

Acute Disease