PubMed Health⌕ Search

Biomedical subjects

S Luger

Publications and source records attributed to S Luger.

17 recordsLinked to original sources
PubMed2002

Bone marrow transplantation for myelodysplastic syndrome--who? when? and which?

Although allogeneic transplantation has resulted in long-term disease-free survival in some patients with myelodysplastic syndromes (MDS), the morbidity and mortality of this approach remains high. Additionally, many patients are not candidates for such an approach because of their age or comorbid factors. Autologous transplantation and the use of reduced intensity conditioning prior to allogeneic stem cell transplantation has provided less toxic alternatives as well as increased the numbers of patients eligible for some form of transplantation. While bone marrow transplantation clearly has a role in the treatment of MDS, the decision to proceed to transplantation is not always easy and the optimal approach has not been clearly defined. Improvement in patient selection and novel approaches to transplantation will hopefully allow for more effective, less toxic results.

Bone Marrow Transplantation↗
PubMed2000

A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma.

This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 x 10(6) CD34+ cells/kg using stem cell factor (SCF; 20 microg/kg/day) plus filgrastim (G-CSF; 10 microg/kg/day) vs filgrastim alone (10 microg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 10(6) CD34+ cells/kg to proceed to transplant (16% vs 26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 x 10(6)/kg vs 0.48 x 10(6)/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 x 10(6)/kg vs 2.4 x 10(6)/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy.

Adult↗
PubMed2000

Soluble interleukin-2 receptor concentration as a biochemical indicator for acute graft-versus-host disease after allogeneic bone marrow transplantation.

When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that results in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%) by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100% increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial measurements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.

Acute Disease↗
PubMed1999

Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells.

Effective host T lymphocyte sensitization to malignant cells depends on successful antigen presentation. In this study, we examined the capacity of malignant myeloid progenitor cells of patients in the chronic phase of chronic myelogenous leukemia (CML) to acquire characteristics of activated dendritic cells (DCs) after intracellular calcium mobilization, thereby bypassing a need for third-party antigen-presenting cells. Treatment of purified CD33(+) CML cells from 15 patients with calcium ionophore (CI) consistently resulted in de novo expression of the costimulatory molecules CD80 (B7.1) and CD86 (B7.2), CD40 and the DC-specific activation marker CD83, as well as marked up-regulation of MHC class I and II molecules and the adhesion molecule CD54. Most of these changes occurred within 24 hr of treatment. Morphologically, CI-treated CML cells developed long dendritic projections similar to those seen in mature DCs. Functionally, CI-treated CML cells provided stimulation of allogeneic T lymphocytes 10- to 20-fold that of untreated CML cells or untreated monocytes. Fluorescent in situ hybridization of CI-activated CML cells confirmed their leukemic origin by displaying the typical bcr/abl fusion signal. No difference in bcr/abl translocation percentages between untreated and CI-treated CML nuclei was observed. These observations indicate that calcium mobilization may constitute a valuable approach for rapidly and reliably generating CML-derived DCs for immunotherapy of CML.

Antigens, CD↗
PubMed1999

Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I(+), IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia.

To determine activation status of the IL-2R-associated (Jak/STAT) pathway in the HTLV-I infected cells, we examined tyrosine phosphorylation of Jak3, STAT3, and STAT5 in several HTLV-I(+) T-cell lines and in uncultured leukemic T cells isolated from patients with adult T-cell lymphoma/leukemia (ATLL). Constitutive basal phosphorylation of Jak3 and, usually, STAT3 and STAT5 was detected in all four IL-2-independent cell lines tested, but in none of the three IL-2-dependent cell lines. Similarly, there was no detectable basal phosphorylation of Jak3 and STAT5 in the leukemic cells from ATLL patients (0/8 and 0/3, respectively). However, stimulation with IL-2 resulted in Jak3 and STAT5 phosphorylation in both leukemic ATLL cells and IL-2-dependent lines. Furthermore, expression of SHP-1 phosphatase which is a negative regulator of cytokine receptor signaling, was lost in most IL-2 independent cell lines (3/4) but not in the leukemic ATLL cells (0/3). Finally, the HTLV-I(+) T-cell lines (313) but not the control, HTLV-I(-) T-cell lines were resistant to rapamycin and its novel analog RAD. We conclude that (1) HTLV-I infection per se does not result in a constitutive phosphorylation of the Jak3, STAT3, and STAT5 proteins; (2) malignant transformation in at least some cases of ATLL does not require the constitutive, but may require IL-2-induced, activation of the IL-2R Jak/STAT pathway; and (3) there are major differences in T-cell immortalization mechanism(s) which appear to involve SHP-1 and target molecules for rapamycin and RAD.

DNA-Binding Proteins↗
PubMed1999

Rituximab (anti-CD20 monoclonal antibody) therapy for progressive intermediate-grade non-Hodgkin's lymphoma after high-dose therapy and autologous peripheral stem cell transplantation.

We evaluated the response and toxicity of rituximab in the setting of progressive intermediate grade non-Hodgkin's lymphoma (NHL) after autologous peripheral stem cell transplantation (PSCT). Seven patients with a median age of 59 years (45-62), ECOG performance status 0-1, and CD20-positive diffuse large cell lymphoma with progression after PSCT were treated. All patients initially received 4-weekly infusions of rituximab (375 mg/m2). The maximum response was three CR and four PR. Median progression-free survival was 197 days (range 60-282). With a median follow-up of 204 (115-299) days, the patients' disease status is classified as two CR, one PR, and four PD. Four of five patients with ECOG performance status of 1 prior to treatment showed improvement to status 0 after treatment with rituximab. While follow-up is short, these results suggest that rituximab has significant activity in intermediate-grade non-Hodgkin's lymphoma that has relapsed after PSCT.

Antibodies, Monoclonal↗
PubMed1999

Pharmacokinetics, dosimetry, and initial therapeutic results with 131I- and (111)In-/90Y-labeled humanized LL2 anti-CD22 monoclonal antibody in patients with relapsed, refractory non-Hodgkin's lymphoma.

The pharmacokinetics, dosimetry, and immunogenicity of 131I- and (111)In-/90Y-humanized LL2 (hLL2) anti-CD22 monoclonal antibodies were determined in patients with recurrent non-Hodgkin's lymphoma. Fourteen patients received tracer doses of 131I-hLL2 followed 1 week later by therapeutic doses intended to deliver 50-100 cGy to the bone marrow. Another eight patients received (111)In-hLL2 followed by therapy with 90Y-hLL2 also delivering 50 or 100 cGy to the bone marrow. The blood T(1/2) (hours) for the tracer infusions of 131I-hLL2 was 44.2 +/- 10.9 (mean +/- SD) compared with 54.2 +/- 25.0 for the therapy infusions, whereas the values were 70.7 +/- 17.6 for (111)In-hLL2 and 65.8 +/- 15.0 for 90Y-hLL2. The estimated average radiation dose from 131I-hLL2 in tumors >3 cm was 2.4 +/- 1.9 cGy/mCi and was only 0.9-, 1.0-, 1.1-, and 1.0-fold that of the bone marrow, lung, liver, and kidney, respectively. In contrast, the estimated average radiation dose from 90Y-hLL2 in tumors >3 cm was 21.5 +/- 10.0 cGy/mCi and was 3.7-, 2.5-, 1.8-, and 2.5-fold that of the bone marrow, lung, liver, and kidney, respectively. No evidence of significant anti-hLL2 antibodies was seen in any of the patients. Myelosuppression was the only dose-limiting toxicity and was greater in patients who had prior high-dose chemotherapy. Objective tumor responses were seen in 2 of 13 and 2 of 7 patients given 131I-hLL2 or 90Y-hLL2, respectively. In conclusion, 90Y-hLL2 results in a more favorable tumor dosimetry compared with 131I-hLL2. This finding, combined with the initial anti-tumor effects observed, encourage further studies of this agent in therapeutic trials.

Adult↗
PubMed1998

Phase II study of mitoguazone, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with diffuse histologic subtypes of non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Study (PE481).

Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.

Adult↗
PubMed1997

Taste- and odor-reactivity in heroin addicts.

Opiates in general, and heroin in particular, are known to induce compulsive drug-seeking and drug-taking behavior. Addiction is accompanied by psychobiological processes which may distort perception of sensory stimuli. Gustatory and olfactory stimuli are hedonically polarized and therefore most appropriate for the assessment of the organism's reactivity to "useful" and "harmful" chemosensory events. Previous studies revealed that psychophysical self-estimates and reflectory facial expressions mirror with comparable reliability the hedonics of the perceived taste and odor sensations. In the present study both cognitive verbal and reflectory facial expressions of a group of: a) heroin addicts were recorded and compared to those of a group of b) detoxified former addicts and to c) a group of matching controls. Results show that all three groups differentiate between pleasant, indifferent and aversive tastes and odors. Active addicts estimated sweet taste and savory smells as being somewhat more pleasant, and bitter and sour tastes and a putrid odor as less unpleasant than did the other two groups. The reflectory facial displays of addicts were less expressive and discriminative than those of the two other groups. Taste- and odor-induced facial displays are known to be controlled primarily by the brainstem. The findings indicate that heroin-addiction affects brain-mechanisms, which mirror taste- and odor-hedonics. Modulation of the phylogenetically ancient, sensory-motor coordinations was found to be of a different pattern than that of the cortically-controlled cognitive reactions.

Adult↗
PubMed1997

An optimization study on unprogrammed cryopreservation of human CD34+ bone marrow cells and their subsequent storage in an -80 degrees C mechanical freezer.

Among the factors which enable successful bone marrow transplantation, the ability to store and subsequently recover sufficient viable marrow cells to reestablish hematopoiesis is crucial. In most centers, marrow is typically prepared for long term storage by programmed, controlled rate freezing with subsequent placement into the vapor phase of liquid nitrogen. Though clearly effective, this procedure is time consuming and equipment intensive. Since cost containment is an important issue for all medical procedures, we evaluated the utility of a faster and less costly method to accomplish the same purpose. We found that when CD34+ bone marrow cells are immediately frozen and stored at -80 degrees C, the number and quality of stem/progenitor cells recovered after thawing was comparable to those reported recovered after conventional processing. Herein we report optimized conditions for cryopreserving and storing CD34+ bone marrow cells at -80 degrees C and for subsequent thawing of the stored product. With these methods post-thaw recovery of CFU-Mix, for example, equaled or exceeded 80% of predicted numbers, even after six months of storage. Further, though progenitor cell recovery does not necessarily correlate with speed of engraftment, these results nonetheless suggest that storage of human CD34+ cells at -80 degrees C in a mechanical freezer is a convenient, inexpensive, and reliable method for storing marrow for transplantation.

Antigens, CD34↗
PubMed1996

4-Hydroperoxycyclophosphamide purged autologous bone marrow transplantation in non-Hodgkin's lymphoma patients at high risk of bone marrow involvement.

Between June 1990 and January 1994, 19 patients with non-Hodgkin's lymphoma (NHL) at high risk for bone marrow involvement underwent 4-hydroperoxycyclophosphamide (4-HC) purged bone marrow transplantation. Eleven patients had low grade, seven intermediate grade and one high grade NHL and 7/19 patients had received three or more previous chemotherapeutic regimens. Four patients were transplanted in first partial remission (PR) and the remainder in responsive relapse. Fourteen patients had bone marrow (BM) involvement at diagnosis and/or at relapse. The median times to granulocyte and platelet recovery were 26 and 29 days, respectively. There were two toxic deaths and one complete responder developed secondary AML at 31 months post-BMT. Seventeen of 18 evaluable patients achieved a complete remission (CR) and one patient a PR. Fourteen patients (74%) are progression-free at a median follow-up of survivors of 34 months (range 29-55). The 3 year event-free (EFS) and overall survival (OS) probabilities are both 67%. No statistically significant difference was seen between EFS or OS and BM involvement or histologic grade at diagnosis. At 29 months, 4/7 patients with a morphologically involved BM harvest had relapsed or died compared to 1/12 patients with negative BM (P = 0.03). These results are encouraging and warrant further investigation of 4-HC purging in NHL.

Adult↗
PubMed1995

Bloodstream invasion in early Lyme disease: results from a prospective, controlled, blinded study using the polymerase chain reaction.

PURPOSE: The purposes of this study were to determine (1) the optimal techniques for and potential diagnostic usefulness of the polymerase chain reaction (PCR) in early Lyme disease, and (2) the true frequency and clinical correlates of PCR-documented blood-borne infection in the dissemination of Lyme disease. PATIENTS AND METHODS: We performed a prospective, controlled, blinded study of PCR, culture, and serology on fractionated blood samples from 105 patients; 76 with physician-diagnosed erythema migrans and 29 controls. Clinical characteristics of the patients were obtained with a standardized data entry form and correlated with results of the laboratory studies. RESULTS: Only 4 of the 76 (5.3%) patients with erythema migrans were culture positive; however, 14 of 76 (18.4%) had spirochetemia documented by PCR of their plasma. None of 29 controls were PCR or culture positive (P = 0.007, versus patients). PCR-documented spirochetemia correlated with clinical evidence of disseminated disease; 10 of 33 patients (30.3%) with systemic symptom(s) were PCR positive compared to 4 of 43 (9.3%) without such evidence (P = 0.02). PCR positivity was more frequent among patients with each of four specific symptoms: fever, arthralgia, myalgia, and headache (all P < 0.05). A higher total number of symptoms (median 2.5 in PCR-positive patients versus 0 in PCR-negative controls; P < 0.01) and the presence of multiple skin lesions (37.5% of patients with multiple, versus 13.3% of patients with single lesions [P = 0.04] were also correlated with PCR positivity. Patients with both systemic symptoms and multiple skin lesions had a 40% PCR-positivity rate; however, 4 of 42 (9.5%) asympatomatic patients with only single erythema migrans lesions were also PCR positive. In multivariate analysis using logistic regression, the number of systemic symptoms was the strongest independent predictor of PCR positivity (P = 0.004). CONCLUSIONS: PCR detection of Borrelia burgdorferi is at least three times more sensitive than culture for identifying spirochetemia in early Lyme disease and may be useful in rapid diagnosis. PCR positivity significantly correlates with clinical evidence of disease dissemination. Bloodstream invasion is an important and common mechanism for the dissemination of the Lyme disease spirochete.

Bacteremia↗
PubMed1991

Geographical and temporal distribution of babesial infection in Connecticut.

Human babesiosis was first recognized in Connecticut in 1989, nearly 15 years after Lyme disease, a similarly transmitted spirochetosis, was detected in the state. To determine the seroprevalence for the babesial pathogen and whether it was recently introduced, we used an indirect immunofluorescence assay to test for Babesia microti antibody in 1,285 Connecticut residents. Four groups were studied: I, people seropositive for Lyme disease, tested from 1986 to 1989; II, randomly selected outpatients tested in 1989; III, college students residing in Connecticut, tested from 1959 to 1989; and IV, healthy people without tick exposure or Lyme disease, tested in 1989. Babesia seropositivity was significantly higher in group I (9.5%; n = 735) than in groups II (2.6%; n = 304, P less than 0.0001) and III (1.0%; n = 206, P less than 0.0001) but not group IV (2.5%, n = 40). Babesia seropositivity for group I ranged from 9.2 to 10.2% between 1986 and 1989, and Babesia seropositivity for group III ranged from 0% between 1959 and 1985 to 2.9% between 1986 and 1989. There is a considerable risk of babesial infection among residents of the Connecticut mainland who are seropositive for Lyme disease, a risk that appears to have remained constant over the past 5 years.

Animals↗