Recurrent venous thromboembolism in patients with and without anticoagulation after inferior vena caval filter placement.

AIM: The aim of this study was to compare the rate of recurrent venothromboembolic (VTE) events and factors contributing to VTE events in patients with inferior vena caval (IVC) filters on chronic anticoagulation to those in whom anticoagulation was discontinued. METHODS: Retrospective cohort study of 353 patients who received IVC filters between 1986 and 2002. RESULTS: Anticoagulation status was available for 304 patients (132 on coumadin anticoagulation therapy and 172 who did not receive any anticoagulation therapy) whose IVC filters were placed within 30 days of their qualifying thromboembolic event. Two-year event-free survival for the anticoagulated group was 80.6% (95% confidence interval--CI--76.9, 84.3] and was 67.8% (95% CI 63.2, 72.3) for the non-anticoagulated group. Patients who had Greenfield filter had a higher, but not statistically significant different, rate of recurrence compared to those with other types of filters (hazard ratio 1.4; 95% CI 0.9, 2). The rate of recurrent VTE events was independent of age, gender, smoking status, or underlying medical condition. CONCLUSIONS: Among those with IVC filters, long-term anticoagulation therapy prolonged event-free survival for up to 2 years but did not prevent recurrent VTE events.

Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly.

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.

Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia.

The value of maintenance therapy after the achievement of complete remission in adult acute nonlymphocytic leukemia (ANLL) has never been clearly established. A randomized Eastern Cooperative Oncology Group (ECOG) study of postremission therapy compared outcomes in patients who received no further therapy to those administered long-term maintenance chemotherapy. Adverse results in the group administered no further therapy led to early termination of this trial after only 51 patients were randomized. Patients receiving no postremission therapy experienced significantly inferior remission durations (P = .002) compared with patients receiving maintenance therapy. All 26 patients in the group administered no postremission therapy have relapsed, with a median duration of remission of 4.1 months. In contrast, four of 25 patients (16%) who received maintenance therapy remain disease free, with a median duration of remission of 8.1 months.

High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia.

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.

Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group.

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.

The limited utility of fibrinogen I 125 leg scanning.

Using venography as the reference procedure, this study examined the utility of fibrinogen I 125 scanning for the detection or demonstration of deep venous thrombosis. The results demonstrate the inability of leg scanning to detect accurately the presence or absence of thrombi in the deep venous system. Most striking was the lack of sensitivity of this procedure in areas where the propensity for embolization is greatest. Sensitivity is extremely low in the anatomic areas where leg scanning demonstrates reasonable specificity. The results are nearly identical in the extremity not operated upon. The validity of all prior studies relying heavily or exclusively on 125I leg scans to determine the presence or absence of thrombi must be critically reassessed.

Risk assessment model for venothromboembolism in post-hospitalized patients.

AIM: Venothromboembolism (VTE) is an important condition in hospitalized patients accounting for significant morbidity and mortality, and the risk of VTE often continues post-hospitalization. Although risk assessment models have been developed to predict the risk of deep venous thrombosis (DVT) in hospitalized patients, no models have been developed that determine the risk of DVT during the post-hospitalization period. The objective of this study was to create a risk profile using risk factor assessment that could be used to predict which patients are at highest risk of developing DVT within 60 days following hospital discharge. METHODS: The computerized medical records of 380 patients (190 with DVT and 190 without DVT) who received care from 1995-2002 and were subsequently re-hospitalized within 60 days of discharge were retrospectively reviewed. Univariate and multivariate logistic regression analyses were conducted to identify risk variables related to VTE. A novel risk assessment model was created using risk factors from the logistic regression analyses. RESULTS: The prevalence of VTE was found to be 93.2% (69/74) in the high-risk category, 52.9% (109/206) in the moderate-risk category, and 12% (12/100) in the low-risk category. CONCLUSIONS: Once validated, this risk assessment model may be applied to identify patients who may be at increased risk of developing VTE post-hospitalization. Those at high risk should be considered for anticoagulation therapy during the post-hospitalization period. Availability of a risk profile using risk factor assessment to guide decisions related to anticoagulation therapy will have important ramifications relative to patient outcomes including morbidity, mortality, and reductions in VTE-associated cost.

Diphenylhydantoin and fragility of erythrocytes in normal subjects and in patients with hereditary spherocytic anemia.

To study the effects of diphenylhydantoin (Dilantin, DPH) on membrane function, DPH was incubated with erythrocytes from normal individuals and from patients with congenital spherocytic hemolytic anemia and osmotic fragility measured. The resulting curves show that DPH reduces the osmotic fragility of normal and spherocytic erythrocytes. In the presence of ouabain, DPH still had a protective effect on erythrocytes even though ouabain alone increases hemolysis of erythrocytes at certain saline concentrations. This study shows that erythrocyte fragility can be manipulated in vitro and provides a basis for studies in vivo.

Treatment of adult patients with acute lymphocytic leukemia in relapse.

Thirty-eight patients with a diagnosis of relapsed acute lymphocytic leukemia were accrued to a treatment program of reinduction therapy by the Eastern Cooperative Oncology Group (ECOG). A combination of mitoxantrone, etoposide (VP-16), and high-dose cytarabine (ARA-C) were administered over a five day period. Thirty-four patients were eligible for follow-up subsequent to treatment. Twenty-seven patients were in first relapse and seven were in second relapse. Fifteen of the thirty-four patients treated were given two cycles of induction chemotherapy. The complete remission (CR) rate for the entire group treated was 17%. The median duration of the CR was 2.4 months and the estimated median survival for first relapse patients was 4.5 months and 5.0 months for second relapse patient group. There were five deaths attributable to toxicity associated with the chemotherapy. The study emphasizes the difficulty in achieving durable remissions in adult patients with relapsed ALL.

Aggressive chemotherapy in the treatment of Burkitt's and non-Burkitt's undifferentiated lymphoma.

Because of the aggressive nature and frequent recurrence of malignant lymphomas of the undifferentiated type, we used a multi-drug induction chemotherapy regimen that has met with some success in children with similar type of histopathology followed by intensification and 8 cycles of consolidation chemotherapy in an attempt to prolong the duration of remission and survival in adult patients with this diagnosis. Fifty-one patients (median age 35 years) with undifferentiated malignant lymphoma were collected over a 4 year period (1984-1988) and entered into a phase III protocol done under the auspices of the Eastern Cooperative Oncology Group (ECOG). Six patients who had their diagnosis made at surgery and had resection of their tumor were excluded from analysis of response to therapy. Sixty percent of the patients had Stage IV disease. Sixteen patients had marrow involvement and five had central nervous system (CNS) disease. None of the patients received CNS radiation therapy. The 45 patients evaluated for response showed a response rate of 67% (30/45) and a complete response rate of 40% (18/45). Thirteen responders continue disease-free with a median follow-up of > 40 months and have an estimated 5 year survival of 80%. Only two treatment related deaths were reported for the entire group. Patients with undifferentiated non-Burkitt's lymphoma had a longer survival than those with undifferentiated Burkitt's. We concluded that adult patients with undifferentiated lymphomas could be treated successfully with an aggressive multi-drug chemotherapy regimen, consisting of multiple alternating cycles of non-crossed-resistant chemotherapy. Toxicity with this aggressive prolonged regimen was acceptable.

Multi-drug resistance in chronic lymphocytic leukemia.

We evaluated 45 chronic lymphocyte leukemia (CLL) patients for the presence of multi-drug resistance (MDR) by the ex vivo techniques: 1) a functional assay utilizing doxorubicin (dox) retention with modulation; 2) a cytotoxicity assay (MTT) with modulation; 3) and four monoclonal antibodies. Ex vivo tests were correlated with disease stage and prior treatment, and were repeated as patients became resistant to alkylating agents, fludarabine and VAD chemotherapy (infusion of vincristine, dox, and oral dexamethasone). The majority of patients (64.4%) were in early stage and were untreated (62.2%). P-glycoprotein (p-gp 170) was detected most frequently by the monoclonal antibody MRK-16 (48%) and by functional modulation of dox retention by PSC-833 (40.6%) and by functional modulation of the MTT assay with vincristine (0.29) and dox (0.39) with PSC-833 at 1.0 microg/mL. Functional modulation of dox retention with PSC-833 was significantly associated with stage, but not with either the MTT assay or any of the monoclonal antibodies. None of the tests correlated with prior chlorambucil treatment. Correlation of dox retention with the monoclonal antibodies was mild to moderate and became stronger following chlorambucil treatment. Three patients who became resistant to VAD were found to express p-gp 170. We conclude that MDR can frequently be detected in patients with CLL. Furthermore, the expression of p-gp 170 increases with advancing stage, but not prior alkylating agent therapy. The functional expression of p-gp 170 increases with advancing stage and prior treatment and correlates well with monoclonal antibody detection (especially MRK-16). Patients who become resistant to VAD more frequently express p-gp 170 by a variety of techniques. PSC-833 is a more potent modulator of MDR than cyclosporin-A (CsA) ex vivo, and correlates better with stage of disease.

Gardner-Diamond syndrome with multiple glomus tumors.

The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. The diagnosis of multiple glomus tumors was confirmed by biopsy, and the Gardner-Diamond syndrome was confirmed by reproduction of the painful purpura with the intradermal injection of the patient's sonicated erythrocytes.

Atypical purpura fulminans with benign monoclonal gammopathy.

A 67-year-old woman with a history of thrombophlebitis had been taking warfarin sodium for 1 1/2 years when she developed multiple skin lesions resembling warfarin-induced skin necrosis or purpura fulminans. Despite discontinuing the warfarin and administering prednisone, the lesions increased in size. Disseminated intravascular coagulation (DIC) was found and resolved with heparin sodium therapy, and her skin lesions healed. This patient was believed to have an atypical form of purpura fulminans rather than warfarin-induced skin necrosis because of the duration of warfarin therapy and the dramatic resolution with heparin. A monoclonal (IgG) gammopathy was found, which stabilized as the skin lesions resolved, and fulfilled the criteria for a benign (asymptomatic) monoclonal gammopathy.

The treatment of older adult patients with acute myeloid leukemia by triple infusion chemotherapy.

Adult patients (> or = 56 years old) with acute myeloid leukemia (AML) received induction therapy consisting of daunorubicin (60 mg/m2), etoposide (80 mg/m2), and cytarabine (200 mg/m2) daily for 5 days by continuous i.v. infusion (120 hours). The initial protocol was modified so that patients who were not hypoplastic after the first cycle of chemotherapy received a second cycle of treatment, utilizing 30 mg/m2 of daunorubicin/24 hours for 5 days plus etoposide and cytarabine as used in the first cycle. Two courses of consolidation with etoposide and cytarabine at the same dose and schedule were given. Patients were then maintained on cytarabine monthly. Twelve of 29 previously untreated patients (41%) achieved complete remission (CR). Excluding patients with secondary AML, 48% of all patients (11/23) achieved CR, including 56% > or = 70 years old. The median duration of CR was 41 weeks and median survival of CR patients was 54 weeks. Six of 13 patients (46%) with relapsed AML achieved CR. Toxicity in these older adult patients has been mild. Two patients (8%) had severe mucositis and one had severe (bloody) diarrhea. Most patients developed a mild transient asymptomatic rash. Triple infusion chemotherapy (TIC) may be as effective as other chemotherapy regimens for AML in older adults and has acceptable toxicity.

Exposure to violence in young inner-city adolescents: relationships with suicidal ideation, depression, and PTSD symptomatology.

This study examined the relationship of exposure to violence to suicidal ideation, depression, and post-traumatic stress disorder (PTSD) symptomatology in 94 young adolescents from an inner-city school. Participants completed self-report measures of the Reynolds Adolescent Depression Scale, the Suicidal Ideation Questionnaire--Junior, Adolescent Psychopathology Scale--Posttraumatic Stress Disorder Subscale, and the Exposure to Violence Questionnaire. Using a hierarchical multiple regression design, exposure to violence demonstrated a unique relationship with PTSD symptomatology. Specifically, the relationship between violence exposure and PTSD symptomatology remained significant after controlling for depression and suicidal ideation severity. Controlling for PTSD symptomatology resulted in nonsignificant relationships between violence exposure and depression and suicidal ideation in adolescents. Additional analyses suggest that PTSD functions as a mediating variable between exposure to violence and depression and suicidal ideation. The implication of these results and suggestions for future research are discussed.

The relationship between posttraumatic stress symptomatology and suicidal behavior in school-based adolescents.

This study investigated the relationship between posttraumatic stress disorder (PTSD) symptomatology and suicidal behavior, specifically suicidal ideation and suicide attempt history, while controlling for depression and gender in 106 adolescents in an urban high school. Participants completed self-report measures of the Adolescent Psychopathology Scales-Posttraumatic Stress Disorder Subscale (APS-PTS), the APS-Suicide Attempt History (APS-SAH), the Suicidal Ideation Questionnaire-Junior (SIQ-JR), and the Reynolds Adolescent Depression Scale (RADS). Analyses were conducted using a hierarchical multiple regression design to account for the relationship between PTSD symptomatology and depression. Regression results showed that after controlling for depression and gender, PTSD symptomatology was significantly related to suicidal ideation and showed a trend toward suicide attempt history. In addition, adolescents with high levels of PTSD symptomatology were more likely than peers with "average" levels of PTSD symptomatology to be currently thinking about suicide and to have made a past suicide attempt. These findings show that PTSD symptomatology has a unique relationship to adolescent suicidal behavior that cannot be explained by depression or gender. The importance of these results and their implications for future research are discussed.

Activity involvement among suicidal and nonsuicidal high-risk and typical adolescents.

The purpose of this study was to compare weekly activities among four groups of randomly selected high-risk and typical high school students: (1) potential dropouts at suicide risk, (2) typical youth at suicide risk, (3) potential dropouts not at suicide risk, and (4) typical youth not at suicide risk. Of the 1,286 participants, 39.4% of the high-risk and 30.1% of typical high school students screened in at suicide risk. Weekly activity comparisons across the four groups showed that suicide-risk adolescents, regardless of potential dropout status, engaged in more solitary activities on weekdays and weekends than did their nonsuicide risk peers. High-risk potential dropout youth engaged in less homework and more social activities during weekdays and weekends than did the typical high school students. These results provide important insight into the weekly activity involvement of at-risk youth while helping to gain a better understanding of suicide-risk adolescents. Implications of these findings are discussed for identifying youth at risk for suicidal behavior and for prevention programming.

A longitudinal investigation of depression, hopelessness, social support, and major and minor life events and their relation to suicidal ideation in adolescents.

The longitudinal relationship of psychological and social-environmental factors with adolescent suicidal ideation over a 1-year-period was examined in a sample of 374 high school students. Students were assessed twice over a 1-year period with measures of depression, hopelessness, major negative life events, daily hassles, social support, and suicidal ideation. At the initial assessment, daily hassles and negative life events for males and social support and depression for females were significant factors related to suicidal ideation levels 1 year later. Changes in depression and hopelessness were significantly related to changes in suicidal ideation over the 1 year interval for males and females. Differences found between males and females in the relationship of psychological and social-environmental variables with suicidal ideation supports the need to examine gender specific relationships when conducting research on suicidal behavior in adolescents.

Treatment of venous thromboembolic disease. A pragmatic approach to anticoagulation and thrombolysis.

Heparin (Lipo-Hepin, Liquaemin Sodium) and warfarin sodium (Coumadin, Panwarfin) are the classic anticoagulants in use for venous thromboembolic disease. They work by modifying the coagulation mechanism, heparin having an immediate effect and warfarin having a more delayed effect. The most common adverse effects of anticoagulation therapy are hemorrhagic complications. Thrombolytic therapy should be considered in all patients with massive pulmonary embolism with hypotension and in patients with deep venous thrombosis in the popliteal area or higher. Such therapy has been shown to help preserve the pulmonary microcirculation after pulmonary embolism and to decrease the incidence of the postthrombotic syndrome following deep venous thrombosis. If certain clinical guidelines are followed rigidly, the incidence of significant bleeding complications is low. Although the use of tissue plasminogen activator in venoocclusive disease has been limited to isolated cases, results have been very promising.

Hematopoietic growth factors. A promising future for use in bone marrow dysfunction.

The clinical future of hematopoietic growth factors appears promising. They will probably achieve broad clinical application in a wide variety of hematologic disorders. Their use in infectious diseases associated with granulocytopenia and in cancer-treatment regimens as adjuvant agents against myelosuppression and perhaps as stimulants of the natural anti-cancer effects of host cells also seems appropriate.