Leukemic gingival infiltrate as an indicator of chemotherapeutic failure following monoclonal antibody therapy: a case report.

Treatment options are limited for patients with relapsed acute myelogenous leukemia (AML), particularly when the disease is refractory to standard cytotoxic chemotherapy. Targeted drug therapy offers the advantage of delivering higher doses of non-cross resistant chemotherapy with potentially less systemic toxicity. Gemtuzumab ozogamicin (Mylotarg, Wyeth-Ayerst Laboratories) is an immunoconjugate that consists of humanized anti-CD 33 antibody linked to the potent anti-tumor antibiotic calicheamicin and has been an effective therapy for some patients with relapsed AML.

Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high-risk breast cancer.

Axillary lymph node involvement in breast cancer is a marker of recurrence risk. Despite aggressive adjuvant therapy, recurrence in patients with four or more involved lymph nodes approaches 50% at 5 years from diagnosis. Markers that can distinguish those likely to relapse from those likely to be cured are needed to tailor therapy and provide accurate prognostic information to patients.

Use of ibritumomab tiuxetan anti-CD20 radioimmunotherapy in a non-Hodgkin's lymphoma patient previously treated with a yttrium-90-labeled anti-CD22 monoclonal antibody.

Ibritumomab tiuxetan is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy-refractory CD20+ B-cell non-Hodgkin's lymphoma. Whereas chemotherapy agents can successfully be used multiple times in a given patient, there are few data on the repeated use of radioimmunotherapy in terms of efficacy or morbidity, and no reports as yet involving radioconjugates that target different antigens We report on a patient who was treated successfully with yttrium-90-labeled humanized anti-CD22 monoclonal antibody (90Y-epratuzumab). Upon relapse 3 years later, the patient was treated again with radioimmunotherapy consisting of 90Y-ibritumomab tiuxetan anti-CD20 monoclonal antibody, with a good response and acceptable bone marrow suppression.

Homocysteine and prothrombin fragment 1+2 levels in patients with veno-occlusive disease after stem cell transplantation.

Veno-occlusive disease (VOD) of the liver remains a major complication after hematopoietic stem cell transplantation (SCT). VOD is thought to develop after hepatic endothelial cells are damaged by high-dose chemotherapy or radiation, causing microthrombosis in hepatic venules. However, the precise mechanisms leading to VOD are not well defined, and a diagnosis is often difficult to establish.

Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation.

We explored the feasibility and toxicity of administering escalating doses of anti-CD3/CD28 ex vivo costimulated T cells as a therapeutic adjunct for patients with relapsed, refractory, or chemotherapy-resistant, aggressive non-Hodgkin lymphoma (NHL) following high-dose chemotherapy and CD34+-selected hematopoietic cell transplantation (HCT). Sixteen patients had infusions on day 14 after HCT of autologous T cells that had been stimulated using beads coated with anti-CD3 and anti-CD28 monoclonal antibodies. At baseline, the subjects had severe quantitative and functional T-cell impairments.

'GVHD': graft-versus-host disease or graft-versus-Hodgkin's disease? An old acronym with new meaning.

The majority of patients with relapsed or refractory Hodgkin's lymphoma (HL) will not be cured with standard therapy. Relapse rates remain high even after autologous stem cell transplantation (SCT), particularly for patients with high-risk disease. Allogeneic SCT offers several potential advantages for patients with HL.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications.

Post-transplant lymphoproliferative disorder: a review.

Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of Epstein-Barr virus-related (EBV) clinical diseases, from a benign mononucleosis-like illness to a fulminant non-Hodgkin's lymphoma. In the setting of hematopoietic stem cell transplantation, PTLD is an often-fatal complication occurring relatively early after transplant. Risk factors for the development of PTLD are well established, and include HLA-mismatching, T-cell depletion, and the use of antilymphocyte antibodies as conditioning or treatment of graft-versus-host disease.

Concurrent administration of interferon alfa-2b and beta-1a.

Objective: To describe the concurrent use of interferon (IFN) alfa and beta in a patient with multiple sclerosis (MS) and chronic myeloid leukemia (CML).

Case Summary: A 60-year-old white man developed CML while receiving IFN beta-1a treatment for MS. The patient was started on IFN alfa-2b 1 million units 3 times weekly with IFN beta-1a 30 micro g weekly.

High rate of invasive fungal infections following nonmyeloablative allogeneic transplantation.

Nonmyeloablative allogeneic transplantation is an emerging therapy for hematologic and solid malignancies and potentially offers patients reduced transplant-related toxicity. Data regarding infectious complications of these protocols are limited, but early studies have demonstrated little infectious morbidity, particularly low rates of invasive fungal infections (IFIs). In the present study, 31 consecutive cases of nonmyeloablative transplantation were reviewed over a 2.

Use of EBV PCR for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients.

Epstein-Barr virus (EBV) is known to be involved in the majority of patients who develop post-transplant lymphoproliferative disorder after solid organ transplant. We conducted a retrospective study to determine the utility of qualitative and quantitative Epstein-Barr virus polymerase chain reaction (PCR) for the diagnosis and monitoring of post-transplant lymphoproliferative disorder in adult solid organ transplant patients. Peripheral blood leukocytes obtained from 35 adult solid organ transplant patients consecutively referred for evaluation of possible post-transplant lymphoproliferative disorder, were tested by EBV PCR at the time of initial evaluation and at time points thereafter.

Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.

Purpose: This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens.

Patients And Methods: Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks.

Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin).

We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101 patients > or =60 years of age with acute myeloid leukemia (AML) in untreated first relapse in three open-label trials. Mylotarg is administered as a 2-h intravenous infusion at 9 mg/m(2) for two doses with 14 days between doses. The overall remission rate was 28%, with complete remission (CR) in 13% of patients and complete remission with incomplete platelet recovery (CRp) in 15%.

Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy.

Nonmyeloablative allogeneic stem cell transplantation (NMASCT) can be used to exploit the graft-versus-tumor (GVT) potential of allogeneic donor cells in the setting of reduced conditioning regimen toxicity. This approach is particularly attractive for patients who have received extensive prior therapy and are poor candidates for traditional allogeneic stem cell transplantation. However, toxicity in heavily pretreated patients remains uncertain.

High-dose chemotherapy and stem cell support for breast cancer: where are we now?

To date, there is no definitive evidence that high-dose chemotherapy and haematopoietic stem cell support offers a survival advantage over conventional-dose chemotherapy for metastatic or high-risk primary breast cancer. Studies of metastatic disease discussed in this review have an adequate duration of follow-up given the short natural history of metastatic breast cancer. Thus, the results of these studies are unlikely to change with a longer observation period.

Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia.

Options for treatment of poor-prognosis or relapsed acute myeloid leukemia (AML) remain limited. Gemtuzumab ozogamicin (Mylotarg, Wyeth-Ayerst, Philadelphia, PA) is an immunoconjugate composed of recombinant humanized murine anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent. Phase II trials have shown the efficacy of gemtuzumab ozogamicin in the treatment of relapsed AML.

Gemtuzumab ozogamicin (Mylotarg) monotherapy for relapsed AML after hematopoietic stem cell transplant: efficacy and incidence of hepatic veno-occlusive disease.

Gemtuzumab ozogamicin (GO) (Mylotarg, CMA-676) is a novel chemotherapeutic agent consisting of an anti-CD33 monoclonal antibody linked to calicheamicin, and is associated with a 30% response rate in patients with CD33-positive acute myeloid leukemia (AML) in first relapse. GO therapy has a 20% incidence of grade 3 or 4 hepatotoxicity, and has recently been associated with hepatic veno-occlusive disease (VOD). The efficacy and toxicity of GO in patients with AML who have relapsed after hematopoietic stem cell transplant (HSCT) is unknown, as this population was largely excluded from phase II studies.

Histamine dihydrochloride and interleukin-2 in the treatment of acute myeloid leukemia.

Despite successful chemotherapeutic remission induction, most patients with acute myeloid leukemia still are destined to die from recurrent and refractory disease. Strategies to prolong remission and improve survival include high-dose chemotherapy, autologous or allogeneic stem cell transplantation, and other immunotherapeutic approaches. The focus on interleukin-2 (IL-2) has arisen from in vitro demonstration of enhancement of tumor-specific cytotoxic T-lymphocyte and natural killer-cell activity after cytokine activation.

Tumor cell depletion of peripheral blood progenitor cells using positive and positive/negative selection in metastatic breast cancer.

Background: The clinical relevance of tumor cell purging of hematopoietic progenitor cell grafts has yet to be conclusively determined. Therefore, in addition to the demonstration that a method for graft purification is capable of removing an adequate number of tumor cells, it is critical that the procedure has as benign an impact upon the hematopoietic repopulating potential of the graft as possible. We evaluated tumor cell depletion, recovery of CD34(+) cells and post transplant engraftment kinetics as accepted measures of the effectiveness of an immunomagnetic bead (positive and positive/negative) purging methodology.

Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens in acute myeloid leukemia.

Gemtuzumab ozogamicin (Mylotarg) is an immunoconjugate composed of a recombinant humanized murine anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent. The aim of this review is to summarize ongoing trials with gemtuzumab ozogamicin in combination with chemotherapy in acute myeloid leukemia (AML) patients. The studies include determination of safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy in previously untreated as well as relapsed and refractory AML patients.

Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study.

Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their delivery was optimized and they were targeted to short-lived proteins encoded by messenger RNA (mRNA) species with equally short half-lives. To test this hypothesis, an ODN targeted to the c-myb proto-oncogene was developed and used to purge marrow autografts administered to allograft-ineligible chronic myelogenous leukemia patients. CD34(+) marrow cells were purged with ODN for either 24 (n = 19) or 72 (n = 5) hours.

High-dose versus standard chemotherapy in metastatic breast cancer: comparison of Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow Transplant Registry.

Purpose: To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC).

Patients And Methods: SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry. Cox proportional hazard regression incorporated potentially confounding effects.

Progressive intermediate-grade non-Hodgkin's lymphoma after high-dose therapy and autologous peripheral stem-cell transplantation: changing the natural history with monoclonal antibody therapy.

The prognosis of patients with progressive intermediate-grade non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) is poor, with survival measured in months. The advent of monoclonal antibody therapy for NHL has created new options for effective therapy with relatively mild side effects. We report on two patients with progressive intermediate-grade NHL after PSCT who were treated with monoclonal antibody therapy.

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer.

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2.

Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial.

Purpose: Although high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse.

Patients And Methods: A randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs.