Biomedical subjects

D Przepiorka

Publications and source records attributed to D Przepiorka.

At least 37 records · Page 2Linked to original sources

PubMed2000

Clinical trials of HER-2/neu-specific vaccines.

Recently there has been a renewed interest in developing vaccines for use in cancer treatment. Part of this interest stems from a better understanding of the immune system, the identification of a number of T-cell-specific tumor antigens, more effective adjuvants, and the ability to construct more immunogenic molecules using recombinant DNA techniques. Studies from several laboratories have shown that breast cancer patients have preexisting immunity to the HER-2/neu oncoprotein receptor (HER-2) in the form of elevated antibody titers and T-cell immunity. Preclinical studies showed enhanced delayed-type hypersensitivity and cytotoxic T-lymphocyte precursors in spleens from animals immunized with several human leukocyte antigen class I and class II peptides derived from the HER-2 protein. Phase I trials of these peptides combined with the cytokine granulocyte-macrophage colony-stimulating factor as a part of therapy in patients with HER-2-positive cancers have shown minimal local toxicity, along with enhanced helper T-cell activity and antibody production in patients with minimal disease. Increases in cytotoxic T-lymphocyte precursor activity were less frequent, but in some cases could be enhanced when patient lymphocytes were incubated ex vivo with the proinflammatory cytokine interleukin-12. Other preclinical studies designed to enhance HER-2 peptide immunogenicity are in progress. Additional current and future clinical trials using HER-2-derived vaccines will be discussed.

Animals↗

PubMed1999

Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation.

We evaluated demographic characteristics and graft composition as risk factors for acute graft-versus-host disease (GVHD) in 160 adult recipients of HLA-identical allogeneic blood stem cell transplants. The patients received a median nucleated cell dose of 7.9 x 10(8)/kg and median C34(+) cell dose of 5.6 x 10(6)/kg. GVHD prophylaxis consisted of cyclosporine (CSA) and steroids, tacrolimus (FK506) and steroids, or FK506 and methotrexate. Grades 2 to 4 GVHD occurred in 31% (95% CI, 23% to 39%), and grades 3 to 4 GVHD in 14% (95% CI, 8% to 20%). In univariate analyses, GVHD prophylaxis with CSA and high CD34(+) cell doses were significant risk factors for grades 2 to 4 GVHD, but diagnosis, age, use of total body irradiation, donor sex, female donor for male recipient, donor parity, donor alloimmunization, viral serology, nucleated cell dose, CD3(+) cell dose, and CD56(+) cell dose did not alter the incidence of GVHD significantly. With a CD34(+) cell dose less than 8 x 10(6) CD34(+) cells/kg, the risk of grades 2 to 4 GVHD was significantly higher for those who received CSA (39%, 95% CI, 21% to 47%) in comparison with those on FK506 (18%, 95% CI, 10% to 26%) (P =.03), but GVHD prophylaxis regimen had less impact with a higher CD34(+) cell dose (overall grades 2 to 4 GVHD rate 52%, 95% CI, 37% to 67%). GVHD prophylaxis and CD34(+) cell dose are independent risk factors for acute GVHD after allogeneic blood stem cell transplantation.

Adolescent↗

PubMed1999

Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study.

Agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder in which patients with poor prognostic features, receiving conventional treatments, have a median survival of less than 3 years. In this retrospective multicenter study, we analyze the results and try to define the indications for allogeneic stem cell transplantation in AMM. From January 1979 to November 1997, 55 patients with a median age of 42 years were transplanted from HLA-matched related (n = 49) or alternative (n = 6) donors for AMM. A multivariate analysis was conducted to identify factors associated with posttransplant outcome. The median posttransplant follow-up was 36 months (range, 6 to 223). The 5-year probability of survival was 47% +/- 8% for the overall group, and 54% +/- 8% for patients receiving an unmanipulated HLA-matched related transplant. The 1-year probability of transplant-related mortality was 27% +/- 6%. Hemoglobin level </=100 g/L and osteomyelosclerosis before transplant adversely affected the outcome. The probability of developing grade III-IV acute graft-versus-host disease (GVHD) was 33% +/- 8%. Sixteen of 45 patients developed extensive chronic GVHD. At last follow-up, 22 patients were in complete histohematologic remission. Treatment failure was observed in 13 cases. Age at transplant and karyotype were predictors of treatment failure. Allogeneic stem cell transplantation is an effective treatment leading to cure in a substantial number of patients with AMM. A better characterization of the variables affecting the posttransplant outcome should lead to a decreased transplant-related mortality and an improvement in these results.

Adult↗

PubMed1999

Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations.

BACKGROUND: T cells present in an allogeneic bone marrow transplant may produce graft-versus-host disease but also contribute to immune reconstitution and enhance engraftment. Our aim was to separate alloreactive from nonalloreactive T lymphocytes, by performing a mixed lymphocyte culture (MLC) stimulation of donor cells, followed by selective depletion of activated cells expressing the high-affinity interleukin 2 receptor. We then characterized the resulting depleted cell fraction. METHODS: Donor peripheral blood mononuclear cells were cocultured with irradiated peripheral blood mononuclear cells from HLA-nonidentical recipient stimulators in an MLC. After 3 days, CD25+ lymphocytes (alloreactive cells expressing the alpha chain of the interleukin 2 receptor) were removed by immunomagnetic separation. The depleted donor fraction and untreated cells were then rechallenged in a secondary MLC with the original irradiated stimulator cells or a third party to assess relative alloreactivity. RESULTS: Inhibition of the secondary MLC and of host-specific cytotoxic activities was observed as well as a disappearance of interleukin 2 receptor-positive cells. Alloreactivity against unrelated third-party cells was preserved. Limiting dilution analysis of residual alloantigen-reactive T lymphocytes demonstrated a 1.3 log reduction of antihost reactivity. The depletion largely removed host-specific alloreactive CD4+ cells. CONCLUSIONS: This method reduces alloreactivity while retaining reactivity against third-party targets. This approach may allow therapeutic infusion of T cells after HLA-nonidentical allografts with a reduced capacity to produce graft-versus-host disease.

Blood Component Removal↗

PubMed1999

Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia.

Thirty-six adults with chronic myelogenous leukemia (CML) in second or greater chronic phase, accelerated phase, or blast crisis underwent marrow or blood stem cell transplantation from an HLA-matched sibling using high-dose thiotepa, busulfan and cyclophosphamide (TBC) as the preparative regimen. All evaluable patients engrafted and had complete donor chimerism. One patient failed to clear meningeal leukemia, and one patient had one of 30 metaphases positive for the Philadelphia chromosome at 2 months post transplant. The remainder of the patients studied had eradication of CML documented by cytogenetics and/or Southern blot for BCR gene rearrangement, and 13 of 15 patients studied became negative for the BCR gene rearrangement by polymerase chain reaction. Three-year relapse rate is 42% (95% CI, 19-64%). The relapse rate was significantly lower for patients transplanted without blast crisis (9% vs 100%, P < 0.001). Eight (22%, 95% CI, 10-39%) patients had severe or fatal veno-occlusive disease (VOD). Elevated liver enzymes within 1 month prior to transplantation and transplantation using marrow were significantly associated with the occurrence of VOD. Three-year survival is 28% (95% CI, 13-43%). Survival was significantly higher for patients transplanted without blast crisis (45% vs 0%, P = 0.01). TBC is an effective preparative regimen for CML in accelerated phase but not refractory blast crisis, and it should be used with caution in patients with prior hepatopathy who have an increased risk of severe VOD.

Adult↗

PubMed1999

Tacrolimus for prevention of graft-versus-host disease after mismatched unrelated donor cord blood transplantation.

Ten children with hematologic malignancies or a storage disease underwent transplantation using cord blood cells from an unrelated donor mismatched for 1 (n = 7) or 2 (n = 3) HLA antigens. The median total nucleated cell dose was 4.0 (range, 2.2-7.1) x 10(7)/kg. GVHD prophylaxis consisted of tacrolimus dose-adjusted to maintain a whole blood level of 5-15 ng/ml with or without methotrexate 5 mg/m2 i.v. on days 1, 3, 6 and 11. Corticosteroids were not administered prophylactically. Median follow-up is 12 months (range, 5-28 months). One patient had autologous recovery and subsequently relapsed 153 days post transplant. For the remainder of the patients, the median time to an ANC >0.5 x 10(9)/l was 21 days (range, 19-38 days), and the median time to platelets >20 x 10(9)/l was 39 days (range, 21-97 days). The actuarial risk of grade 2 GVHD was 77% (95% CI, 49-100%), and no patient had grades 3-4 GVHD. Two patients developed chronic GVHD. The survival rate is 90% (95% CI, 81-100%). The combination of tacrolimus and minidose methotrexate is active for the prevention of severe but not moderate acute GVHD after mismatched unrelated donor cord blood transplantation.

Antimetabolites, Antineoplastic↗

PubMed1999

Cytomegalovirus disease in adult marrow transplant recipients receiving ganciclovir prophylaxis: a retrospective study.

In a retrospective study, we compared the incidence and risk of mortality associated with CMV disease in adult allogeneic BMT and PBSC recipients who received ganciclovir prophylaxis three-times-per-week (78 patients) vs five-times-per-week (137 patients). Active CMV infection occurred in 28 (41%) and 26 (21%) in the three- vs five-times-per-week groups, respectively (P < 0.005). CMV disease developed in 11 (16%) and five (4%) patients who received ganciclovir prophylaxis in the three-times-per-week vs five-times-per-week groups (P < 0.004). The CMV-attributable mortality rate was 1.5% and 12% in the five- vsthree-times-per-week groups, respectively (P < 0.003). Risk factors for CMV disease, significant at the P < 0.05 level in the multivariate analysis, were ganciclovir prophylaxis at three-times-per-week, receiving a T cell-depleted (TCD) marrow, and tacrolimus as prophylaxis for GVHD. These data suggest that ganciclovir five-times-per-week significantly reduced the incidence and mortality of CMV disease in allogeneic BMT and PBSC recipients. However, ganciclovir five-times-per-week was less effective for the prevention of CMV disease in patients receiving TCD marrow or tacrolimus.

Adolescent↗

PubMed1999

Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation.

Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.

Acute Disease↗

PubMed1999

Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide.

Seventeen children with advanced myeloid malignancies (induction failure, relapse, myelodysplasia, secondary AML, or CR >1) received thiotepa 750 mg/m2 i.v., busulfan 12 mg/kg or 640 mg/m2 p.o., and cyclophosphamide 120 mg/kg i.v. as a preparative regimen for allogeneic or autologous hematopoietic stem cell (HSC) transplantation. Of the 15 allogeneic transplants, eight were from matched siblings, one was from a mismatched sibling, and six were from unrelated donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine or tacrolimus and methotrexate. Regimen-related toxicity was common but tolerable, affecting mainly the skin and gastrointestinal tract. Three patients died early and were not evaluable for engraftment; engraftment occurred in the remaining patients. Nine patients with active disease at the time of transplant were evaluable for response; all achieved remission. With a median follow-up of 40 months (range, 10-71 months), nine patients are alive and disease-free. The 3-year actuarial event-free survival was 51% (95% confidence interval (CI) 27-76%). Seven patients died of transplant-related complications: infection (n = 4), chronic GVHD (n = 1), veno-occlusive disease, VOD, (n= 1) and pulmonary alveolar hemorrhage (n = 1). Only one patient had leukemia relapse and died. We conclude that the use of high-dose thiotepa, busulfan and cyclophosphamide is an effective conditioning regimen for childhood myeloid malignancies and may be tested in patients with less advanced disease (eg CR1).

Adolescent↗

PubMed1999

Practical considerations in the use of tacrolimus for allogeneic marrow transplantation.

Tacrolimus has been shown to be more effective than cyclosporine for prevention of acute graft-versus-host disease (GVHD). A number of transplant centers have therefore adopted tacrolimus as standard prophylaxis, but with additional experience, current management of tacrolimus differs from that in the clinical studies. Therefore, a consensus conference was convened to assess the current practices. For prevention of GVHD, conference participants recommended administering tacrolimus at 0.03 mg/kg/day (by lean body weight) i.v. by continuous infusion from day -1 or -2 pretransplant, with day -2 used especially for pediatric patients. Therapeutic drug monitoring was considered essential in the management of patients on tacrolimus. The consensus target range for the whole blood concentration was 10-20 ng/ml. Doses were modified for blood levels outside the target range or for nephrotoxicity, and tacrolimus was discontinued for intolerable tremor, hemolytic uremic syndrome, leukoencephalopathy or other serious toxicity. Tacrolimus was employed most frequently in combination with minimethotrexate (5 mg/m2 i.v. days 1, 3, 6 and 11). Tapering was individualized according to center practice. No patient category was excluded from use of tacrolimus based on age, extent of disease, patient-donor histocompatibility or stem cell source. Tacrolimus was also used successfully for treatment of chronic GVHD. The responsiveness of steroid-refractory acute GVHD was marginal, so it was deemed more prudent to use tacrolimus for prophylaxis instead.

Bone Marrow Transplantation↗

PubMed1999

Relationship of tacrolimus whole blood levels to efficacy and safety outcomes after unrelated donor marrow transplantation.

Tacrolimus has proved effective for preventing acute graft-vs.-host disease (GVHD) after unrelated donor marrow transplantation, but the therapeutic window is apparently narrow. Therapeutic drug monitoring could potentially be used to guide dose modifications, but the optimal target range of tacrolimus blood concentrations is unknown. We determined whether acute GVHD and renal dysfunction correlated with tacrolimus whole blood levels as measured by the IMx assay. Data were analyzed for 97 adults treated in a multicenter trial of tacrolimus and methotrexate or methylprednisolone as GVHD prophylaxis after unrelated donor marrow transplantation. The rate of grades II-IV GVHD was 49%; 81% of patients had a doubling of the serum creatinine; and 61% had a serum creatinine <2 mg/dL. The initial tacrolimus target range for the clinical trial was 10-60 ng/mL. Tacrolimus blood levels were averaged over a 14-day period, and Cox models were used with averaged blood levels as a time-dependent covariate. No significant change was observed in the risks of acute GVHD, doubling of creatinine, need for dialysis, or death over a tacrolimus blood level range of 5-40 ng/mL, but there was a direct correlation between risk of developing a creatinine <2 mg/dL and increasing tacrolimus blood levels (4.7% increased risk for each 1 ng/mL increase in blood concentration, p < 0.001). When the tacrolimus level exceeded 20 ng/mL, there was a 2.2-fold increase in the rate of renal toxicity (p < 0.001), a trend for an increase in mortality (relative risk 3.9, p=0.08), and no impact on the risk of GVHD. This analysis supports 10-20 ng/mL as the therapeutic range of tacrolimus whole blood steady state or trough levels for unrelated donor marrow transplantation.

Adolescent↗

PubMed1999

Tacrolimus vs. cyclosporine immunosuppression: results in advanced-stage disease compared with historical controls treated exclusively with cyclosporine.

A phase HI comparative trial of tacrolimus- vs. cyclosporine-based graft-vs.-host disease (GVHD) prophylaxis for human leukocyte antigen (HLA)-identical sibling bone marrow transplantation showed less GVHD but poorer survival in the tacrolimus arm. To test the comparability of the two treatment arms with respect to baseline survival prognosis, a matched control study using exclusively cyclosporine-treated patients from the International Bone Marrow Transplant Registry (IBMTR) database was performed. Controls were matched (2:1) based on age (within 5 years), disease, and pretransplant disease status. Two-year survival for tacrolimus-treated clinical trial patients was similar to that of their cyclosporine-treated matched controls (27 and 24%, respectively), and 2-year survival of the cyclosporine-treated clinical trial patients was similar to that of their cyclosporine-treated matched IBMTR controls (42 and 45%, respectively). Consistent with the clinical trial results, the cyclosporine-treated IBMTR controls matched to the tacrolimus group had significantly poorer 2-year survival than the cyclosporine-treated IBMTR controls matched to the cyclosporine group (24 and 45%, respectively; p < 0.01). No significant difference was seen in GVHD between the cyclosporine-treated clinical trial patients and their matched controls; however, the tacrolimus-treated clinical trial patients had significantly less GVHD than their cyclosporine-treated IBMTR controls (p < 0.01). These results support the hypothesis that the survival difference in the phase III trial resulted from an imbalance in the underlying risk factors for death in the two groups rather than from the randomized immunosuppressive regimen.

Adolescent↗

PubMed1999

Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma.

BACKGROUND: The combination of carmustine, etoposide, cytarabine and melphalan (BEAM) is an effective autologous transplantation preparative regimen for lymphoma and has little toxicity, but the feasibility and tolerance of BEAM as a preparative regimen for allogeneic transplantation has not been established. PATIENTS AND METHODS: Thirty adults with primary refractory or recurrent intermediate- or low-grade lymphoma were treated on a prospective phase II study with carmustine 300 mg/m2 i.v. day -6, etoposide 200 mg/m2 i.v. followed by cytarabine 200 mg/m2 i.v. twice daily days -5 to -2, melphalan 140 mg/m2 i.v. day -1, and marrow or blood stem cells from an HLA-identical donor on day 0. Tacrolimus and methotrexate were used to prevent graft-vs.-host disease (GVHD). RESULTS: Median time from transplantation was 20 mos (range 6-32 months). Median maximal regimen-related toxicity grade was 2, and four patients (13%) had a grade 3-4 regimen-related toxicity. Two patients had idiopathic interstitial pneumonitis. One patient had primary graft failure, and a second had autologous reconstitution documented at three months posttransplant. Grades 2-4 acute GVHD occurred in 31%, grades 3-4 in 16%, and chronic GVHD in 54%. Day-100 survival was 70%. Twenty-three patients achieved a complete response. The two-year relapse rate was 23%, survival was 48%, and disease-free survival (DFS) was 42%. CONCLUSIONS: BEAM supports engraftment of allogeneic transplants and is a tolerable preparative regimen for allogeneic transplantation for lymphoma.

Adult↗

PubMed1998

A phase II study of BTI-322, a monoclonal anti-CD2 antibody, for treatment of steroid-resistant acute graft-versus-host disease.

BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen on T cells and natural killer (NK) cells, blocks primary and memory alloantigen proliferative responses in vitro. We have evaluated the pharmacokinetics and safety of BTI-322 during treatment of 20 transplant recipients with steroid-refractory acute graft-versus-host disease (GVHD). Treatment consisted of BTI-322 by intravenous (IV) bolus or 30-minute infusion at approximately 0.1 mg/kg/d for 10 days in addition to continuing high-dose steroids and tacrolimus or cyclosporine. Pharmacokinetic sampling was performed in 10 patients; the t1/2 +/- SE was 9.1 +/- 1.3 hours, the Cmax was 2,549 +/- 291 ng/mL, the Vd was 3.97 +/- 0.95 L, and the Vd/kg was 0. 05 +/- 0.01 L/kg. Ten patients experienced transient dyspnea sometimes accompanied by nausea, vomiting, diarrhea, and tachycardia shortly after the initial bolus dose of drug, but serious drug-related adverse events were not seen during the remainder of the infusions. At the end of treatment (day 11), there were six patients with complete responses and five with a reduction in grade of GVHD for a total response rate of 55% (95% confidence interval [CI], 32% to 77%). Antibodies targeting CD2 may be active in the treatment of acute GVHD, and evaluation of a humanized form of BTI-322 is warranted.

Adult↗

PubMed1998

Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation.

We report the results of a phase III open-label, randomized, multicenter trial comparing tacrolimus/methotrexate to cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis after HLA-identical sibling marrow transplantation in patients with hematologic malignancy. The primary objective of this study was to compare the incidence of moderate to severe (grade II-IV) acute GVHD. Secondary objectives were to compare the relapse rate, disease-free survival, overall survival, and the incidence of chronic GVHD. Patients were stratified according to age (<40 v >/=40) and for male recipients of a marrow graft from an alloimmunized female. There was a significantly greater proportion of patients with advanced disease randomized to tacrolimus arm (P = . 02). The incidence of grade II-IV acute GVHD was significantly lower in patients who received tacrolimus than patients in the cyclosporine group (31.9% and 44.4%, respectively; P = .01). The incidence of grade III-IV acute GVHD was similar, 17.1% in cyclosporine group and 13.3% in the tacrolimus group. There was no difference in the incidence of chronic GVHD between the tacrolimus and the cyclosporine group (55.9% and 49.4%, respectively; P = .8). However, there was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (P = . 03). The relapse rates of the two groups were similar. The patients in the cyclosporine arm had a significantly better 2-year disease-free survival and overall survival than patients in the tacrolimus arm, 50.4% versus 40.5% (P = .01) and 57.2% versus 46.9% (P = .02), respectively. The significant difference in the overall and disease-free survival was largely the result of the patients with advanced disease, 24.8% with tacrolimus versus 41.7% with cyclosporine (P = .006) and 20.4% with tacrolimus versus 28% with cyclosporine (P = .007), respectively. There was a higher frequency of deaths from regimen-related toxicity in patients with advanced disease who received tacrolimus. There was no difference in the disease-free and overall survival in patients with nonadvanced disease. These results show the superiority of tacrolimus/methotrexate over cyclosporine/methotrexate in the prevention of grade II-IV acute GVHD with no difference in disease-free or overall survival in patients with nonadvanced disease. The survival disadvantage in advanced disease patients receiving tacrolimus warrants further investigation.

Adolescent↗

PubMed1998

Allogeneic marrow transplantation for myeloproliferative disorders other than chronic myelogenous leukemia: review of forty cases.

The role of allogeneic marrow transplantation as treatment of myeloproliferative disorders other than chronic myelogenous leukemia is not yet determined. At our center, 1 patient with primary myelofibrosis, 1 with mastocytosis, and 4 with myeloid metaplasia have been transplanted using HLA-identical sibling donors. All patients engrafted with full donor chimerism, and morphologic and cytogenetic manifestations of disease in the marrow resolved posttransplant. Three patients died; two with relapse and one from infection. The other three patients are alive in remission at 24+, 28+, and 32+ months posttransplant. Including these cases, a total of 40 patients transplanted for myeloproliferative disorders have been reported. The most common indications for transplantation were cytopenias, increasing blasts in marrow or blood, uncontrolled counts on conventional therapy, poor prognosis cytogenetics, organ dysfunction, and consolidation after induction therapy for blast transformation. Using the outcome data published for these patients, the actuarial estimate of 3-year survival is 55% (95% C.I., 44-76%) with a median reported follow-up of survivors of 21 months (range, 4-158 months). For patients with myeloproliferative disorders and evidence of accelerated disease, HLA-identical marrow transplantation is well tolerated and can result in an extended disease-free survival.

Adult↗

PubMed1998

Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients.

We studied the potential of multidimensional flow cytometry to evaluate the frequency and maturation/activation status of dendritic cells in minimally manipulated peripheral blood mononuclear cell preparations (i.e., only separated on Ficoll-Hypaque) of normal donors and cancer patients. A rare subset of HLA-DR+ leukocytes (less than 1% mononuclear cells) was detected in blood of normal donors that displayed all the features of dendritic cells: these cells had high forward-light-scatter characteristics and coexpressed CD4, CD86 and CD54 surface antigens, but lacked the lineage-associated surface markers of T cells, B cells, monocytes, granulocytes or NK i.e. they were CD3-, CD19-, CD20-, CD14-, CD11b-, CD16-, CD56-). These physical and phenotypic properties were virtually identical to those of immunomagnetically sorted leukocytes characterized as dendritic-cells on the basis of morphology, phenotype and high stimulatory activity in allogeneic mixed-lymphocyte cultures. Using this flow-cytometric approach we observed that the frequency of dendritic cell-like cells in peripheral blood mononuclear cell specimens of cancer patients receiving chemotherapy alone or those recovering from stem cell transplantation was significantly lower than that of normal individuals (mean +/- SE: 0.36 +/- 0.05%, 0.14 +/- 0.06%, and 0.75 +/- 0.04% respectively). Multidimensional flow-cytometric analysis of dendritic cells might represent an important new tool for assessing immunocompetence, and for monitoring the effects of therapeutic regimens on the immune system.

Dendritic Cells↗

PubMed1998

Heat shock protein--peptide complexes as immunotherapy for human cancer.

Heat shock proteins (Hsps), ubiquitous in nature, act as chaperones for peptides and other proteins. They have been implicated in loading immunogenic peptides onto major histocompatibility complex molecules for presentation to T cells. When isolated from tumor cells, Hsps are complexed with a wide array of peptides, some of which serve as tumor-specific antigens. Animal studies have demonstrated that heat shock protein--peptide complexes (HSPPCs) from tumor cells can act as vaccines to prevent or treat tumors. Potent and specific tumor antigens have long been the holy grail in cancer immunotherapy; HSPPCs from tumor cells could become a safe and reliable source of tumor-specific antigens for clinical application.

Animals↗