Showing papers by "Richard E. Champlin published in 2003"

Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies

Abstract: BACKGROUND Caspofungin (CAS) as salvage therapy for refractory invasive aspergillosis (IA) had a response rate of 45% among a heterogeneous group of patients. The use of CAS with other agents is appealing given its unique mechanism of action. Therefore, the authors retrospectively evaluated the efficacy and toxicity of CAS plus liposomal amphotericin B (LipoAMB) in patients with documented (definite or probable) or possible IA. METHODS Patients were evaluable for outcome if they received CAS/LipoAMB for at least 7 days. Patients who received CAS and LipoAMB sequentially were excluded. All patients were evaluable for toxicity. Outcome was assessed weekly and at the end of therapy. Stable disease and progression were considered treatment failures. RESULTS Forty-eight patients with documented (n = 23) or possible (n = 25) IA were identified between March 2001 and December 2001. The majority of the patients (65%) received CAS/LipoAMB as salvage therapy for progressive IA despite 7 or more days of previous LipoAMB monotherapy. The overall response rate was 42%. No significant toxic effects were seen. Factors associated with failure at the end of therapy were documented IA (P = 0.03), significant steroid use before the study (P = 0.02), and duration of combination therapy for less than14 days (P =0.01). The response rate in patients with progressive documented IA was low (18%). CONCLUSIONS The CAS/LipoAMB combination is a promising preemptive therapy for IA and was generally well tolerated. This combination might have limited benefit as salvage therapy for documented IA. Cancer 2003;98:292–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11479

Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma

Abstract: Purpose: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. Patients and Methods: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. Results: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patient...

Hierarchical Bayesian approaches to phase II trials in diseases with multiple subtypes.

Abstract: We propose a methodology for conducting phase II clinical trials in settings where the disease is categorized into multiple subtypes. A hierarchical Bayesian model is assumed for treatment effects within the subtypes. The hierarchical model, which is tailored to each particular application, allows treatment effects to differ across subtypes while assuming a priori that the effects are exchangeable and correlated. Two applications are described. The first is a trial of imatinib for sarcoma in which treatment activity is characterized by a binary indicator of tumour response. The second is a phase II trial of a new preparative regimen for allogeneic bone marrow transplantation in patients with haematologic malignancies, with treatment effect characterized by the mean time from transplant to disease progression or death. The applications illustrate how the hierarchical Bayesian model borrows strength across subtypes.

Tacrolimus‐associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation

Abstract: Neurotoxicity is a significant complication of the use of tacrolimus. From April 1998 to December 2001, we identified 10 patients (six women, four men) who developed 11 episodes of tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) after allogeneic haematopoietic stem cell transplantation for haematological malignancies. The diagnosis was made by characteristic clinical findings (mental status changes, seizures, neurological deficits) with the exclusion of other causes and characteristic imaging findings. The median age was 35.5 years (range 19-57 years). Seven patients received a matched-unrelated donor transplant and three received a cord blood transplant. The overall incidence of PRES was 1.6%, while the incidence in matched-unrelated, mismatched-related and cord blood transplants was 3.5%, 4.9% and 7.1% respectively. Mental status changes, cognitive deficits, seizures and lethargy were the most common clinical findings. Eight of 10 patients had characteristic findings of hyperintensity of the white matter on T2-weighted images and FLAIR (fluid-attenuated inversion recovery) sequence on magnetic resonance imaging of the brain. Serum tacrolimus levels were within the therapeutic range in most patients. Tacrolimus treatment was continued (n = 4) or temporarily withheld (n = 7) for 1-14 d. One patient was changed to cyclosporine. In most patients, subsequent treatment with tacrolimus was well tolerated without recurrence of neurotoxicity.

Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: Feasibility and results

Abstract: Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results

Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score.

Abstract: BACKGROUND The current study was conducted to analyze the long-term results of autologous stem cell transplantation (ASCT) in patients with diffuse mantle cell lymphoma (MCL) in first disease remission. METHODS Thirty-three patients were treated. Thirty-one patients had Ann Arbor Stage III or Stage IV disease. The hyper-CVAD regimen (hyperfractionated intense-dose cyclophosphamide, vincristine, continuous intravenous infusion of doxorubicin, and dexamethasone, alternating with high doses of cytarabine and methotrexate plus leucovorin rescue) was used for cytoreduction before ASCT. Patients were consolidated with high-dose cyclophosphamide (120 mg/kg), total body irradiation, and ASCT. RESULTS At a median follow-up of 49 months, the overall survival and disease-free-survival rates at 5 years were estimated to be 77% and 43%, respectively. Patients whose M. D. Anderson Lymphoma Tumor Score (TS) was ≤ 1 at the time of diagnosis or transplantation experienced longer disease-free survival compared with those whose TS was > 1 (P = 0.02). A β2-microglobulin (β2m)level ≤ 3 mg/L at the time of diagnosis or transplantation was also found to be strongly predictive of longer survival (5-year survival rate of 100% vs. 22% in patients with a β2m level > 3 mg/L) (P = 0.0001). CONCLUSIONS ASCT may prolong the overall survival in a subset of patients with MCL. This improvement has been observed for the most part in patients with low β2m levels (≤ 3 mg/L) and TS (≤ 1). Randomized trials are required to fully assess the benefits of this strategy. Cancer 2003;98:2630–5. © 2003 American Cancer Society.

Adult stem cells and tissue repair

Abstract: Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells.

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

Abstract: In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

West Nile Encephalitis in 2 Hematopoietic Stem Cell Transplant Recipients: Case Series and Literature Review

Abstract: Most human cases of West Nile virus infection are acquired via bites from an infected mosquito. In some cases, infection may also be transmitted by infected blood products or transplanted organs. There have been recent publications suggesting that chemotherapy and immunosuppression may increase a person's risks of developing central nervous system disease if the person is infected with the West Nile virus. Because patients undergoing hematopoietic stem cell transplantation not only are immunocompromised, but also receive multiple blood products, they are at a particularly high risk for acquiring symptomatic disease if exposed to the West Nile Virus. We describe here 2 patients who underwent hematopoietic transplantation at our institution and subsequently developed fatal West Nile virus infections.

Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation. Biology and current indications.

Abstract: High-dose myeloablative therapy with allogeneic hematopoietic transplantation is an effective treatment for hematologic malignancies, but this approach is associated with a high risk of complications. The use of relatively nontoxic, nonmyeloablative, or reduced-intensity preparative regimens still allows engraftment and the generation of graft-vs-malignancy effects, is potentially curative for susceptible malignancies, and reduces the risk of treatment-related morbidity. Two general strategies along these lines have emerged, based on the use of (1) immunosuppressive chemotherapeutic drugs, usually a purine analog in combination with an alkylating agent, and (2) low-dose total body irradiation, alone or in combination with fludarabine (Fludara).

Idiopathic pneumonia syndrome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for high-risk breast cancer.

Abstract: Our aim was to describe the incidence, clinical course, and risk factors for idiopathic pneumonia syndrome (IPS) after high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa followed by autologous stem cell transplantation for high-risk breast cancer. Charts for patients who underwent high-dose chemotherapy for high-risk breast cancer at a single center from 1992 to 2000 were retrospectively reviewed, and potential risk factors for development of IPS were sought with the log-rank test. Of 164 patients reviewed, 20 developed IPS at a median onset of 87 days after the transplant (range, 2-257 days). The actuarial incidence of IPS in the first 100 days after the transplant was 8%, and 95% of patients developed symptoms within the first 6 months after transplant. Patient age, smoking status, breast cancer stage at diagnosis, and pretransplant lung function did not predict development of IPS. Three patients died of progressive pulmonary failure and the IPS resolved in the other 17. We concluded that IPS is an important cause of morbidity and mortality in patients with high-risk breast cancer undergoing high-dose chemotherapy. Given the absence of predictive factors, any pulmonary symptoms appearing in the first year after the transplant should be evaluated carefully.

Unrelated umbilical cord blood stem cell transplant after failure of haploidentical or matched unrelated donor hematopoietic stem cell transplant.

Abstract: Unrelated umbilical cord blood stem cell transplant after failure of haploidentical or matched unrelated donor hematopoietic stem cell transplant

Treatment of relapsing refractory diffuse large cell lymphoma after matched unrelated donor bone marrow transplant with immunosuppression withdrawal and rituximab.

Abstract: A 31-year-old man with a diffuse large-cell lymphoma in first refractory relapse received a bone marrow transplant (BMT) from a matched unrelated donor using CAMPATH-1H, carmustine, etoposide, cytarabine and melphalan as conditioning regimen, and methotrexate and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. The transplant was complicated by grade II skin acute GVHD. Lymphoma relapse occurred 4 months post-transplant. Immunosuppression withdrawal plus rituximab induced a complete response. He remains in complete remission (CR) 11 months post-immunosuppression withdrawal and 15 months post-transplant.

Quantitative Determination of Bcl-2 Expression in AML Cell Lines and in Normal and Leukemic Progenitor Cell Compartments by Laser Scanning Cytometry: Comparison with Flow Cytometry and Western Blot

Abstract: Laser Scanning Cytometry (LSC) is a newly developed microscope-based and computerized system that directly analyzes up to 3- color fluorescence simultaneously from single cells attached to slides. It permits correlations of quantitative cytometric data with morphology and with cytogenetic abnormalities determined by FISH. The data generated by LSC is equivalent to those obtained by flow cytometry in principle. In this study, Bcl-2 expression was measured in five leukemia cell lines by flow cytometry (FCM), LSC, and western blot. The order of Bcl-2 expression in cell lines from highest to lowest is HL60- DOX, OCI/AML3, HL60, MO7E, and TF-1. There was an excellent correlation of results of LSC vs. western blot, R2=0.97; FCM vs. western blot, R2=0.85; FCM vs. LSC, R2=0.83 (all p values <0.05). We then studied Bcl-2 expression in normal and AML progenitor cell populations. Bcl-2 expression was measured by LSC and western blot for CD34+/CD38+ and CD34+/CD38- cells after FACS-sorting. In normal bone marrow, Bcl-2 was significantly higher in CD34+/CD38+ than in CD34+/CD38- cells (p=0.009). Significant differences in Bcl-2 expression levels were noted in CD34+/CD38- cells between AML and normal bone marrow (NBM) populations (p=0.02), and AML-PB and NBM (p=0.005). All sorted populations contained 25% to 76.5% leukemia cells, based on FISH analysis. We conclude that LSC is a powerful technique for the analysis of gene expression in small numbers of FACS-sorted progenitor cells. It also allows correlations with morphology and cytogenetic abnormalities. The differential overexpression of Bcl-2 protein in CD34+/CD38- AML vs. normal bone marrow cells supports the concept of Bcl-2 as a novel target in the treatment of AML.

Non-Myeloablative Stem Cell Transplantation for Acute Myelogenous Leukemia

Abstract: Nonmyeloablative allogeneic transplantation is a new strategy designed to exploit the graft-versus-leukemia effect of donor immune cells. There is substantial clinical and experimental data demonstrating the potency of graft-versus-leukemia (GVL) effect. The most direct evidence comes from the observation that patients who relapse after allogeneic stem cell transplantation can achieve remission by infusing additional donor lymphocytes [1, 2]. Also, patients who develop graft-versus-host-disease after allogeneic transplantation have a significantly lower risk of disease relapse, and those receiving T-cell depleted allografts have an increased risk of relapse [3, 4]. These observations propelled several investigators to propose that graft-versus-leukemia effect may be sufficient to induce long-term disease control in patients with hematologic malignancies.