Rapid engraftment after allogeneic transplantation of density-enriched peripheral blood CD34+ cells in patients with advanced hematologic malignancies.

Background: Acute graft versus host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Preclinical studies have suggested that a T-cell subset with a CD4-/CD8- double-negative (DN) T-cell phenotype is capable of suppressing GVHD. Double-negative T cells can be mobilized into the peripheral blood with granulocyte colony-stimulating factor (G-CSF) and enriched by density centrifugation.

Impact of admission body weight and chemotherapy dose adjustment on the outcome of autologous bone marrow transplantation.

We performed a retrospective analysis of 473 consecutive adult patients undergoing autologous bone marrow transplantation for hematologic malignancies between 1988 and 1995. The analysis examined whether significant deviation from ideal body mass index is associated with a decrease in event-free survival (EFS), an increase in nonrelapse mortality (NRM) including late toxicities and second malignancies, or relapse. Chemotherapy dosing in underweight and overweight patients is administered based on the relationship of admission body weight (ABW) to ideal body weight (IBW).

Granulocyte colony-stimulating factor-induced comobilization of CD4- CD8- T cells and hematopoietic progenitor cells (CD34+) in the blood of normal donors.

The feasibility of transplantation of HLA-matched hematopoietic progenitor cells from the blood of normal donors given granulocyte colony-stimulating factor (G-CSF) has been reported recently. In the current study, the changes in T-cell subsets as well as CD34+ cells were determined in one blood volume leukapheresis products of six normal individuals given G-CSF. Examination of the T-cell subsets in the leukapheresis products showed three different patterns: one in which a discrete population of CD4- CD8- alphabeta T cells was found in addition to the typical CD4+ and CD8+ T cells in the unfractionated as well as in high- and low-density cells; a second in which the discrete population of CD4- CD8- alphabeta T cells was predominant only in the low-density fractions; and a third in which a discrete population of CD4- CD8- T cells was not observed.

Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies.

Purpose: To determine the effect of age on the outcome of autologous bone marrow transplantation (ABMT) and/or peripheral-blood progenitor-cell (PBPC) transplantation.

Patients And Methods: A retrospective analysis was performed on 500 consecutive patients who ranged in age from 1 to 65 years (median, 40) with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), multiple myeloma (MM), or acute nonlymphoblastic leukemia (AML) who underwent autologous hematopoietic-cell transplant procedures at Stanford University Medical Center.

Results: The actuarial 5-year event-free survival (EFS) rate was 44%, the relapse rate 47%, and the regimen-related mortality (RRM) rate 8.

Preemptive ganciclovir administration based solely on asymptomatic pulmonary cytomegalovirus infection in allogeneic bone marrow transplant recipients: long-term follow-up.

The use of ganciclovir at the time of cytomegalovirus (CMV) infection but before disease onset has been termed "preemptive" therapy. This preemptive ganciclovir administration has been shown to be an effective method for preventing severe CMV disease after allogeneic bone marrow transplantation (BMT), but the optimal method of CMV surveillance is not clear. The purpose of this study was to evaluate effectiveness, side effects, and long-term outcome of preemptive ganciclovir therapy in allogeneic BMT recipients when ganciclovir is prescribed solely on the basis of CMV detection in day +35 bronchoalveolar lavage (BAL).

Multiple cycles of high dose chemotherapy supported by hematopoietic progenitor cells as treatment for patients with advanced malignancies.

Background: Retrospective studies suggest that dose intensity is an important determinant of outcome in the treatment of patients with a variety of malignant diseases such as breast cancer, ovarian cancer, and lymphoma. Unfortunately, these results have not been clearly substantiated in prospective randomized trials. One problem with these studies may be that the degree of dose escalation is not sufficient to result in an improved outcome because the chemotherapy doses are limited by hematopoietic toxicity.

Enrichment of bone marrow and blood progenitor (CD34+) cells by density gradients with sufficient yields for transplantation.

We have evaluated the use of iso-osmolar Percoll density gradients to enrich CD34+ hematopoietic progenitor cells and to reduce T cells for purposes of bone marrow or mobilized peripheral blood cell transplantation (BMT or PBCT). Samples from 12 normal BM donors and 11 patients undergoing mobilization of PB cells using chemotherapy and G-CSF were placed over a five-step density gradient from 40 to 50% Percoll. In BM, low-density fractions 1 to 3 (40 to 45% Percoll) accounted for 3% of starting nucleated cells with a 10- to 20-fold enrichment of hematopoietic progenitors (CD34+ cells) and a 20-fold reduction of CD4+ and CD8+ T cells.

Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin's lymphoma.

High-dose chemotherapy with or without radiotherapy followed by autologous transplantation of hematopoietic progenitor cells is an effective treatment for patients with high-risk or relapsed non-Hodgkin's lymphoma. Chemotherapy and/or hematopoietic growth factors have been used to mobilize progenitor cells in the peripheral blood for transplantation. However, the mobilized blood cell products have been found to be frequently contaminated with tumor cells, and techniques have not been developed to purge tumor cells from these products.

Granulocyte colony-stimulating factor after allogeneic bone marrow transplantation.

Hematopoietic growth factors have been shown to be effective in reducing the period of neutropenia after autologous bone marrow transplantation (BMT). Initial concerns over potential aggravation of graft-versus-host disease (GVHD) and increase in the incidence of relapse in patients with myeloid leukemias influenced the number of studies using hematopoietic growth factors after allogeneic BMT. We report the experience with 50 patients treated at a single institution using granulocyte colony-stimulating factor (G-CSF) after allogeneic sibling (n = 30) and matched unrelated (n = 20) BMT.

Role of etoposide (VP-16) in preparatory regimens for patients with leukemia or lymphoma undergoing allogeneic bone marrow transplantation.

In 1983, we began a series of clinical trials with the goal of reducing the relapse rate following allogeneic BMT for hematologic malignancies. Because of its anti-leukemic activity, the drug VP-16 was chosen and combined with total body irradiation (TBI). The first series (trial I) consisted of patients who had advanced leukemia.

Subcutaneous low dose arabinosyl-cytosine and oral idarubicin in high risk adult acute myelogenous leukemia.

In order to further explore low dose chemotherapy for high risk acute myelogenous leukemia (AML), low dose Ara-C and oral idarubicin (LAI) were given to 33 patients of 24-84 (median 66) years with AML after myelodysplastic syndrome (MDS) (12 patients), refractory AML (13 patients), and AML with contraindications to intensive chemotherapy (8 patients). Patients received 1 to 4 cycles of Ara-C 10 mg/m2 q 12 h s.c.

Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86).

In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP).

Response of osteosarcoma and Ewing sarcoma to preoperative chemotherapy: assessment with dynamic and static MR imaging and skeletal scintigraphy.

In 15 osteosarcomas and six Ewing sarcomas, response to preoperative chemotherapy was assessed with magnetic resonance (MR) imaging without and with gadolinium diethylenetriaminepentaacetic acid (DTPA) enhancement and with dynamic Gd-DTPA studies, and the results were compared with the scintigraphic findings. All studies were obtained prior to and following preoperative chemotherapy. Static MR imaging was of little value for assessment of response; reduction in signal intensity within soft-tissue masses on the T2-weighted spin-echo images indicated response with a sufficient degree of accuracy (71%) but low sensitivity, whereas an increase in signal intensity after Gd-DTPA administration indicated zones of viable tissue with low specificity.

Musculoskeletal neoplasms: static and dynamic Gd-DTPA--enhanced MR imaging.

Static and dynamic magnetic resonance imaging studies were performed in 69 patients with bone and soft-tissue tumors. T1-weighted spin-echo (SE) imaging after intravenous administration of gadolinium diethylenetriaminepentaacetic acid (DTPA) improved the differentiation of necrotic from viable areas; the contrast-to-noise ratio (C/N) between tumor and muscle was an average of 44% lower compared with that in T2-weighted SE imaging. The C/N between tumor and bone marrow or fatty tissue was 43% and 37% lower, respectively, compared with that in nonenhanced T1-weighted SE imaging.

[Results of treatment in primary disseminated osteosarcoma. Analysis of the follow-up of patients in the cooperative osteosarcoma studies COSS-80 and COSS-82].

Since the long-term disease-free survival rate in adjuvantly treated osteosarcoma has nowadays reached a level of about 70%, increasing interest is also being directed towards primarily disseminated forms of the disease. Primary metastases, which were confined to the lungs in 42 cases, were detected in 59 out of 421 patients from the prospective therapy trials COSS-80 and COSS-82. The primary tumors were more frequently localized in the proximal femur and flat bones as compared to patients without detectable metastases at diagnosis.