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P H Wiernik

Publications and source records attributed to P H Wiernik.

At least 19 recordsLinked to original sources
PubMed2001

Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide.

Arsenic trioxide is used in clinical trials in the treatment of relapsed and resistant cases of acute promyelocytic leukemia. Adverse effects from arsenic in these studies have been multisystemic. Arsenic is known to cause corrected QT-interval prolongation and T-wave changes, but the potential for serious ventricular arrhythmias is less well understood. Torsades de pointes, a form of ventricular tachycardia, has been reported with arsenic poisoning but not at therapeutic doses used in protocols for hematologic malignancies. We describe 3 patients in whom this arrhythmia developed while they were treated with arsenic trioxide. Early recognition of the arrhythmia or correction of contributory factors is important because arsenic induced ventricular arrhythmias are known to be resistant to most chemical methods and electrical cardioversion.

Adult↗
PubMed2001

Rare adult acute lymphocytic leukemia with CD56 expression in the ECOG experience shows unexpected phenotypic and genotypic heterogeneity.

Expression of CD56, a marker of natural killer (NK) cells, in acute lymphocytic leukemia (ALL) is rare and, to date, has been described only in non-B lineage ALL. Among 194 patients with CD56 analysis on the ongoing Eastern Cooperative Oncology Group (ECOG) ALL trial, E2993, 6 cases of CD56+ ALL were found (3.1%) with a median of 95% of blast cells expressing CD56, compared with a median of 1% of blast cells in CD56- ALL (P = 0.0001). FAB-L2 characteristics dominated, without granulation. Blast cells from four CD56+ patients expressed T-cell antigens at variable levels of maturation. A clonal rearrangement of the T-cell receptor beta (TCRbeta) gene was detected only in one patient. TCRbeta variable gene usage studies in this and one other CD56+ ALL patient demonstrated a significantly perturbed usage pattern in both patients when compared with control lymphocytes. The two remaining cases typed as early pre-B ALL (CD19+, CD10+), with one case co-expressing CD7. Cytogenetically, 4 patients were normal, 1 complex abnormal, and 1 Philadelphia chromosome positive. Epstein-Barr virus (EBV) sequences were detected in one T- and both B-lymphoid cases. Our data suggest that CD56 is expressed at a precursor stage common to the T- and the B-cell lineage.

Adult↗
PubMed2001

Treatment of human immunodeficiency virus-related lymphoma.

In newly diagnosed human immunodeficiency virus (HIV)-positive patients with non-Hodgkin's lymphoma (NHL), standard lymphoma regimens yield approximately a 50% complete response (CR) rate and an overall median survival of < or = 9 months. Treatment results of relapsed patients are extremely poor. Regimens that appear more effective than standard therapy have usually been investigated only in patients with relatively high CD4 counts. An exception is a regimen consisting of a continuous 96-hour infusion of cyclophosphamide, doxorubicin, and etoposide (CDE). A 62% CR rate was achieved in 21 patients with a median CD4 count of 87/microL, and the median overall survival was 18 months. In another study of 25 patients, didanosine (ddI) was added to CDE and was shown to cause less myelosuppression without compromising efficacy. Other studies suggest that highly active antiretroviral therapy (HAART) can be combined with intensive chemotherapy regimens, with improved efficacy attributed to less frequent dosage reduction of chemotherapeutic agents. More recently, autologous and syngeneic bone marrow transplantation have been explored in a handful of patients with acquired immunodeficiency syndrome (AIDS)-related NHL with promising results. Data on whether widespread use of HAART decreases the incidence of HIV-positive NHL are conflicting. Some clues from recent studies suggest we are close to an answer: (1) protease inhibitors significantly improve survival of HIV-positive patients with NHL; (2) only one of eight recent cases of HIV-positive men with NHL received HAART compared with greater than 70% of HIV-positive men free of NHL; and (3) no prior HAART independently predicted for AIDS-related NHL development. On the other hand, Hodgkin's disease may be increasing in frequency in HIV-positive patients as the incidence of NHL declines. It is hypothesized that more effective reconstitution of the immune system with HAART may facilitate the inversion of these incidences. Future prospective studies will hopefully answer these questions.

Anti-HIV Agents↗
PubMed2001

Toxicity and response evaluation of the interferon inducer poly ICLC administered at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a report of two clinical trials of the Eastern Cooperative Oncology Group.

PURPOSE: Phase II studies were conducted to evaluate the safety and efficacy of the interferon inducer Poly ICLC at low doses in advanced renal cancer and relapsed or refractory lymphoma. PATIENTS AND METHODS: Twenty-nine patients with advanced renal carcinoma and eleven patients with lymphoma were treated with poly ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three days apart until progression or unacceptable toxicity. RESULTS: There were no objective responses. Six patients with renal carcinoma had stable disease as best response with one patient receiving 62 weeks of therapy. Toxicity included grade 3 anemia in 8 patients and grade 4 anemia in one patient. All patients were anemic prior to entry with a median grade 2 anemia at baseline. Grade 4 neutropenia, thrombocytopenia and injection site pain occurred in one patient each. Grade 3 fever, chills or fatigue occurred in four, three, and three patients respectively. Any grade fever occurred in 10 patients (25.6%) and any grade chills occurred in 9 patients (23.1%). CONCLUSION: Poly ICLC at this dose and schedule is well tolerated in both patient populations and is inactive in renal carcinoma.

Adult↗
PubMed2001

N-Methylformamide in advanced squamous cancer of the uterine cervix: an Eastern Cooperative Oncology Group phase II trial.

PURPOSE: Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. PATIENTS AND METHODS: Eligibility for this trial required bidimensionally measurable squamous or adenosquamous cell cancer of the uterine cervix incurable by surgery or radiation therapy, ECOG performance status of < or = 2, no prior NMF and no more than one prior chemotherapy regimen. Patients received NMF at 2000 mg/m2 intravenously over 15-30 minutes days 1, 8 and 15. The cycle was repeated every 42 days. A single dose escalation of 25%, 500 mg/m2 was made after the first cycle if the toxicities did not exceed grade I for hepatic toxicity and grade II for nausea and vomiting. RESULTS: From July 1987 through September 1998, 21 patients with advanced squamous cell carcinoma of the uterine cervix were entered on study. Two patients were ineligible because there was no pretreatment SGOT on one and the other deteriorated prior to drug approval. Therefore, 19 patients were include in the analysis of response and survival. Four were inevaluable, three due to inappropriate tumor evaluation and one secondary to grade III vomiting, who went off study. These patients were included in the denominator while computing the results. There were 2 deaths, one due to pulmonary hemorrhage from perforation during central venous insertion and one due to disease. 30% (6/19) patients had toxicities, Eastern Cooperative Oncology Group (ECOG) grade III or higher and 2 of these patients suffered multiple grade III toxicities. There were no complete or partial responses. CONCLUSION: In this population, NMF in the dose and schedule employed exhibited no clinical activity.

Aged↗
PubMed2001

Hairy cell leukemia in first cousins and review of the literature.

Familial hairy cell leukemia (HCL) occurs rarely. So far, 26 familial instances of HCL (in 12 families) have been reported in the literature. The consistent human leukocyte antigen (HLA) linkage could not be established in most cases of familial HCL. History of exposure to organic chemicals or employment in woodworking or farming was noted in only two out of 11 affected families. We present two familial cases of HCL as well as a thorough literature review. An influence of HLA or farming themselves on a predisposition to HCL remains unproven but does not rule out an HLA-linked and as yet unidentified gene responsible for increased disease susceptibility. HCL in families is unlikely to be due to random patterning, but there are insufficient data so far to decisively incriminate either HLA-related or environmental causative factors.

Genetic Linkage↗
PubMed2001

Anticipation in familial chronic lymphocytic leukaemia.

Anticipation, a phenomenon in which an inherited disease is diagnosed at an earlier age in each successive generation of a family, has been demonstrated in certain heritable neurological disorders and in multiple myeloma, non-Hodgkin's lymphoma and other haematological neoplasms. The present study was conducted to determine whether anticipation occurs in familial chronic lymphocytic leukaemia (CLL). Fourteen published reports of multigenerational familial CLL were analysed for anticipation, together with 10 previously unreported families with familial CLL, and the difference in disease-free survival between generations was determined. The difference between age at onset for each affected parent-child pair was tested against the null hypothesis that there was no difference in age at onset. The age at onset of the studied cases was also compared with that of the Surveillance Epidemiology and End Results (SEER) Program of the U.S. National Cancer Institute. The median ages at onset in the child and parent generations of all families (51.0 and 72.0 years respectively) were significantly different (P < 0.000001), and the null hypothesis was rejected (P < 0.000001). A significant difference was observed between the ages of onset of the child generation and the SEER population (P < 0.00001), but not between the parent generation and the SEER population. Anticipation characterizes familial CLL.

Age of Onset↗
PubMed2001

Systemic lupus erythematosus and B-cell hematologic neoplasm.

The association of systemic lupus erythematosus (SLE) and B-cell malignancy is widely reported in the literature. Here we report nine cases of concurrent of SLE or discoid lupus erythematosus (DLE) and lymphoma or plasma cell disorder. A MEDLINE search was done using the keywords, 'SLE' and 'lymphoma' and the characteristics of all identified cases were summarized and analyzed, along with data from our own cases. Numerous variants of B-cell malignancies were encountered in these patients. B-cell malignancy occurs after the diagnosis and treatment of SLE in most reported cases, although it may precede SLE, or occur synchronously with it. The age at onset of the B-cell neoplasm in SLE patients is similar to that in the general population. Mortality in patients with both diseases is associated with progressive B-cell neoplasm, sepsis secondary to either disease, or both. B-cell malignancy and SLE seem to run independent clinical courses rather than being affected by each other. The use of immunosuppressive drugs is common in patients with SLE diagnosed prior to B-cell lymphoma, arguing that the effect of immunosuppression on the pathogenesis of lymphoma can not be excluded. Three areas worthy of study regarding the probable mechanisms for the occurrence of SLE and B-cell malignancies are discussed. A tumor suppressor gene PTEN may link the two disorders via a defective apoptosis pathway to eliminate hyperactive B and T cells in SLE. The accumulation of clonally expanded hyperactive B-cells that recognize self-antigens in the lymph nodes of SLE may predispose these B-cells to DNA breaks, facilitating tumorigenesis. Lastly, EBV infection, found to have a high prevalence in SLE patients, may serve as a common etiological factor in both disorders.

Adult↗
PubMed2001

Bleomycin, lomustine, cyclophosphamide, vincristine, procarbazine and prednisone (BLEO-CCVPP) in patients with Hodgkin's disease who relapsed after radiotherapy alone: a long-term follow-up study of the Eastern Cooperative Oncology Group (E3481).

Thirty-three evaluable patients with Hodgkin's disease who failed radiotherapy were treated on this phase II study with bleomycin, lomustine, cyclophosphamide, vincristine, procarbazine and prednisone given every 28 days for a minimum of eight courses. Twenty-five patients (76%; 95% CI=55.6-87.1%) achieved a complete remission, the median duration of which cannot yet be determined, but the probability of remaining in continuous complete remission at 10 years is.64. The median survival from entry on this study for all evaluable patients is 10 years, and 12 patients were alive at the time of this analysis with a median follow-up for them of 15.5 years. Of the 22 patients who died, 11 died of progressive or recurrent Hodgkin's disease and 11 died of other causes including 7 second primary neoplasms and at least one myocardial infarction. Both are now well known late complications of Hodgkin's disease treatment.

Adolescent↗
PubMed2000

Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience.

Acute megakaryocytic leukemia (AMegL) is a rare subtype of acute myeloid leukemia (AML) evolving from primitive megakaryoblasts. Because of its rarity and the lack of precise diagnostic criteria in the past, few series of adults treated with contemporary therapy have been reported. Twenty among 1649 (1.2%) patients with newly diagnosed AML entered on Eastern Cooperative Oncology Group (ECOG) trials between 1984 and 1997 were found to have AMegL. The median age was 42.5 years (range 18-70). Marrow fibrosis, usually extensive, was present in the bone marrow. Of the 8 patients who had cytogenetic studies performed, abnormalities of chromosome 3 were the most frequent. The most consistent immunophenotypic finding was absence of myeloperoxidase in blast cells from 5 patients. In the most typical 3 cases, the leukemic cells were positive for one to 2 platelet-specific antigens in addition to lacking myeloperoxidase or an antigen consistent with a lymphoid leukemia. Myeloid antigens other than myeloperoxidase and selected T-cell antigens (CD7 and/or CD2) were frequently expressed. Induction therapy included an anthracycline and cytarabine in all cases. Complete remission (CR) was achieved in 10 of 20 patients (50%). Two patients remain alive, one in CR at 160+ months. Resistant disease was the cause of induction failure in all but 3 patients. The median CR duration was 10.6 months (range 1-160+ months). The median survival for all patients was 10.4 months (range 1-160+ months). Although half of the patients achieved CR, the long-term outcome is extremely poor, primarily attributable to resistant disease. New therapeutic strategies are needed.

Adolescent↗
PubMed2000

Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome.

We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95)

Adolescent↗
PubMed2000

Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483).

The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III study in patients with relapsed/refractory acute myeloid leukemia (AML) to evaluate whether administration of repeated courses of low-dose cytarabine (LDAC) maintenance therapy after induction of complete remission in advanced AML would improve disease-free and overall survival. Patients with AML in second/later relapse or refractory disease were first treated with a combination of high-dose cytarabine and amsacrine. Those who achieved complete remission were then randomized to observation or to receive LDAC, 10 mg/m2 subcutaneously twice a day x2 21 days every 2 months until relapse occurred. Of 86 patients eligible for randomization, 41 patients were assigned to receive LDAC and 45 patients to observation. The median disease-free survival was 7.4 months for patients assigned to LDAC compared to 3.3 months for patients receiving no additional therapy, P= 0.084. The median survival from randomization was 10.9 months and 7.0 months for patients receiving LDAC maintenance chemotherapy and observation, respectively (P= 0.615). The data from this study suggest that LDAC maintenance therapy given to patients with advanced AML who achieve complete remission can increase disease-free survival compared to observation, but does not improve overall survival. Nevertheless, because of the ineffectiveness and toxicity of intensive post-remission chemotherapy in this circumstance, LDAC maintenance therapy, a tolerable outpatient regimen, offers the potential for improved quality of life.

Acute Disease↗
PubMed2000

Duration of second complete remission compared with first complete remission in patients with acute myeloid leukemia. Eastern Cooperative Oncology Group.

The prognosis for patients with acute myeloid leukemia in first relapse is generally poor. The ability to induce a second complete remission (CR) with the same chemotherapy used in initial induction therapy is limited. Remission inversion rate, defined as achieving a longer second CR than the first CR in response to standard chemotherapy for relapse, is important in assessing studies of novel chemotherapy or immunologic treatment strategies for patients with relapsed disease. One hundred and twenty-four patients entered on two Eastern Cooperative Oncology Group (ECOG) studies for patients with relapsed AML were analyzed to determine the remission inversion rate. Twenty-two of the 124 patients (18%; 95% confidence interval 12-26%) experienced a longer second CR duration than the first CR duration by at least 2 months. Inversion of CR duration is thus not a rare event. The inversion frequency reported here establishes a baseline upon which future studies in relapsed disease need to be defined.

Acute Disease↗
PubMed2000

Age of onset evidence for anticipation in familial non-Hodgkin's lymphoma.

Anticipation, a phenomenon in which an inherited disease is diagnosed at an earlier age in each successive generation of a family, has been demonstrated in certain neurological and haematological disorders. This study was conducted to determine whether anticipation occurs in familial non-Hodgkin's lymphoma (NHL). Eleven published reports of multigenerational familial NHL were analysed for evidence of anticipation, together with 18 previously unreported families with familial NHL. Differences in disease-free survival between generations were determined. The difference between age at onset for each affected parent-child pair was tested against the null hypothesis that there was no difference in age at onset. These analyses were also performed separately using only parent-child pairs with age of onset > 25 years to avoid ascertainment bias. In addition, the age at onset distribution of the studied cases was compared with that of the Surveillance Epidemiology and End Results (SEER) Program using data for 1973-98. The median ages at onset in the child and parent generations of all families (48.5 and 71.3 years respectively) and in the selected pairs (52.5 and 71.5 years respectively) were significantly different (P < 0.000002 and P < 0.000001 respectively). The null hypothesis was rejected for all (P < 0.000001) as well as selected pairs (P < 0.000003). A significant difference was observed between the ages of onset of the child generation and the SEER population (P < 0.009), but not between the parent generation and the SEER population. Anticipation occurs in familial NHL, which suggests a genetic basis for it.

Age of Onset↗
PubMed2000

Current status of and future prospects for the medical management of adenocarcinoma of the exocrine pancreas.

Adenocarcinoma of the exocrine pancreas is one of the most refractory neoplasms to medical treatment. Although of marginal value, 5-fluorouracil (5-FU) alone or in combination with other agents or modalities has been the standard surgical adjuvant approach to localized unresectable tumor as well as the standard treatment for disseminated pancreatic cancer. Recently, a new chemotherapeutic agent, gemcitabine, has been shown to be somewhat more effective than 5-FU against metastatic pancreatic cancer. Treatment with gemcitabine usually results in a greater likelihood of objective response and better symptom control than treatment with 5-FU or drug combinations that include 5-FU. However, treatment with gemcitabine does not improve overall survival of patients with disseminated neoplasm. Newer promising agents such as 9-nitrocamptothecin have recently entered clinical trials, and novel modalities (e.g., gene therapy) are nearing full-scale clinical trial. There are reasons to believe that these and other new initiatives may soon significantly improve the medical management of adenocarcinoma of the exocrine pancreas.

Adenocarcinoma↗
PubMed2000

Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient.

DNA sequences with very high similarity (95-98%) to the mouse mammary tumor virus (MMTV) ENV gene have been amplified by PCR in 38.5% of human breast tumors and in <2% of normal breast tissue (Wang et al., Cancer Res., 55: 5173-5179, 1995). Intrigued by these findings, which suggested an exogenous viral etiology for a certain percentage of human breast tumors, we have screened a panel of human breast tumors and normal breast tissue for the presence of MMTV-like DNA sequences. Using similar PCR procedures and stringent hybridization techniques, we have detected the presence of MMTV-like ENV gene sequences in 37% of the human breast tumors that we have analyzed. DNA sequencing has shown these sequences to be 99% homologous to the BR6 strain of MMTV and 100% homologous to the GR and C3H strains of MMTV. We have not detected these MMTV-like sequences in normal breast tissue. However, we have detected these sequences by PCR and stringent hybridization in a T-cell lymphoma of a breast cancer patient who was simultaneously diagnosed with both diseases. Our results support the possibility of an exogenous retroviral etiology for a certain percentage of human breast tumors. Our results also suggest that a similar exogenous retroviral etiology may exist for certain human T-cell lymphomas. In many inbred strains of mice, both breast cancer and T-cell lymphoma are caused by MMTV, hence, in a certain percentage of humans, one or both of these diseases may be caused by an MMTV-like retroviral entity.

Adult↗