In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine.

Recent data in mice have shown that early administration of recombinant human interleukin-2 (rIL-2) provides significant protection from lethal graft-versus-host disease. Because of the potential clinical importance of these findings, it will be important to assess the effectiveness of this therapy in a large animal preclinical bone marrow transplantation model. We report here our initial studies of the in vitro and in vivo effects of rIL-2 in miniature swine.

Automated processing of human bone marrow can result in a population of mononuclear cells capable of achieving engraftment following transplantation.

A concentrate of mononuclear bone marrow cells is often desired for ex vivo treatment with pharmacologic agents, monoclonal antibodies, cytokines, and other agents prior to transplantation. A method has been developed for automated separation of mononuclear cells from large volumes of harvested bone marrow. A programmable instrument originally designed for clinical ex vivo cell separation and the plasma-pheresis of patients and blood donors was adapted to permit rapid preparation, in a closed sterile system, of a bone marrow product enriched with mononuclear cells.

Retrograde intubation of the trachea.

Successful intubation can be accomplished in the majority of patients via direct laryngoscopy. However, situations frequently arise in which simple orotracheal intubation is contraindicated or impossible. In these situations retrograde tracheal intubation may be of particular use.

Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels.

Multiple benefits of intravenous immunoglobulin (IVIG) therapy after marrow transplantation have been reported, including decreased incidence of acute graft-versus-host disease (GVHD), infection, sepsis, cytomegalovirus (CMV) pneumonitis and platelet use. To test the hypothesis that the observed beneficial effects of IVIG are related to the serum IgG levels achieved, we followed IgG levels (pre-infusion, 1 h and 24 h post-infusion) in 45 consecutive marrow transplant recipients. IVIG 500 mg/kg was given weekly for six doses starting day -8 pre-transplant, then every other week for a total of 11 doses.

Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis.

Intensive chemoradiotherapy conditioning regimens and acute graft-versus-host disease (GVHD) are both associated with significant morbidity and mortality after bone marrow transplantation. In this study, we investigated whether the conditioning regimen affected the development of acute GVHD. Thirty-four patients, four with severe aplastic anemia and 30 with a lymphohemopoietic malignancy, were prepared for transplantation either with cyclophosphamide (CY) alone, with CY combined with total body irradiation (TBI) or CY combined with etoposide and either TBI or busulfan.

Transfusion-induced graft-versus-host disease in patients with malignant lymphoma. A case report and review of the literature.

A case of transfusion-induced graft-versus-host disease (GVHD) occurring in a 31-year-old female with Hodgkin's disease in complete remission is reported. Clinical features are similar to 19 other reported cases of transfusion-induced GVHD associated with malignant lymphoma. The lack of relationship with underlying histology or disease stage and the nearly uniformly fatal outcome underscores the importance of prophylactic irradiation of blood products given to patients with malignant lymphoma undergoing therapy.

Incapacitating peripheral neuropathy as a manifestation of chronic graft-versus-host disease.

A 35-year-old caucasian man developed mild and transient signs of chronic graft-versus-host disease (GVHD) 5 months after bone marrow transplantation. At 16 months he presented with painful cramps in hands, feet, and truncal muscles. Electrophysiological studies revealed generalized sensory neuropathy.

Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer.

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer.

Effect of tumor necrosis factor on the human fibrinolytic system.

We report the effects on the fibrinolytic system of intravenous (IV) recombinant tumor necrosis factor-alpha (rTNF-alpha) infusions in patients with advanced cancers. During a phase I clinical trial of rTNF-alpha, the plasma fibrinolytic system was closely monitored, measuring tissue-type plasminogen activator (tPA) antigen, plasminogen activator (PA) inhibitor activity, and plasma fibrinolytic activity. Thirteen patients with refractory malignancies received 40, 80, or 160 micrograms/m2 rTNF-alpha as 2-hour IV infusions.

Escalating doses of etoposide with cyclophosphamide and fractionated total body irradiation or busulfan as conditioning for bone marrow transplantation.

In a phase I study 28 patients with lymphohematopoietic malignancies were treated with escalating doses of etoposide combined with cyclophosphamide 120 mg/kg and either fractionated total body irradiation (TBI) 1320 cGy in 11 fractions (n = 17) or busulfan 16 mg/kg (n = 11). Twenty transplants were allogeneic, seven autologous and one syngeneic. The maximally tolerated dose of etoposide in combination with TBI and cyclophosphamide was 60 mg/kg; at etoposide doses of 65 mg/kg three patients developed life-threatening or fatal mucosal toxicity.

High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study.

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v.

Pulmonary fibrosis after bone marrow transplantation responsive to treatment with prednisone and cyclosporine.

Interstitial pneumonitis and biopsy-proven pulmonary fibrosis developed in a 35-year-old man with acute myeloblastic leukemia 4 months after conditioning with total body irradiation, etoposide and cyclophosphamide and allogeneic marrow transplantation from an HLA-identical sister. The patient had no evidence of graft-versus-host disease. Under treatment with cyclosporine and prednisone the patient became asymptomatic and radiographic changes of the chest normalized.

Rapid infusion amphotericin B: effective and well-tolerated therapy for neutropenic fever.

A retrospective analysis was carried out of the results of 115 intensively-treated cancer inpatients receiving 91 treatment courses of amphotericin B given in an empirical fashion. Amphotericin B was administered over 1.5 to 2 hours at a dose of 0.

Acute esophageal stricture after bone marrow transplantation.

Gastrointestinal complications following bone marrow transplantation are common and may result from the conditioning regimen, immunosuppression, graft-versus-host disease, or a combination of these factors. These effects may be acute (mucositis, enteritis, esophagitis) or delayed (xerostomia, stricture formation) in onset. We describe here a case of esophageal stricture developing within 1 month of allogeneic bone marrow transplantation.

Treatment of myelodysplastic syndromes with low-dose oral 6-thioguanine.

Several cytotoxic agents when used in vitro in very low concentrations have been shown to induce differentiation of leukemic cells. We treated 18 patients with myelodysplastic syndromes with low-dose oral 6-thioguanine (6-TG; 20 to 60 mg daily). Four patients demonstrated significant improvement in peripheral blood counts.