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The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte–colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m² over 3 hours (total dose of 14 g/m²), plus mesna at a dose of 0.56 g/m² prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 μg/kg/day was administered subcutaneously on days 6–15. Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0–14%) and 1 was an unconfirmed response (3%; 95% CI, 5–14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3–7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6–9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma. Cancer 2003;98:331–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11512

Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell expansion characterized by high levels of circulating monoclonal antibody that affects 3% of individuals over the age of 70. Although this is considered benign, a high percentage of MGUS patients develop a debilitating peripheral autoimmune neuropathy and have a significantly increased risk for progression to multiple myeloma. Here we show that the relative numbers of the CD30+T cell subset and levels of CD30 expression are elevated in activated lymphocytes from normal aged individuals (≥60 years) and in MGUS patients, when compared to younger controls. PBL from MGUS patients and age-matched controls produced comparable levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a soluble form of CD30 ligand (sCD30L/CD8α) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8α alone. This capability was associated with the unique presence of CD30+T cells in the peripheral blood of MGUS patients. Furthermore, a higher percentage of activated MGUS T cells express CD30 when activated by incubation with idiotype-expressing autologous serum (68 ± 13) than those activated by anti-CD3 plus IL-2 (43 ± 7). These results indicate that quantitative alterations in CD30+T cells accompany aging and MGUS and that these cells may contribute to the chronic activation of B cells though the production of IL-6.

The two mouse myeloma globulins, MOPC-104E IgM and J558 IgA, have antibody specificity to α-1,3-dextran and represent two idiotypes of antidextran antibodies. The results of the reported experiments indicate that idiotype suppression could be achieved by prior immunization of BALB/c mice with either 104E IgM or J558 IgA. After this immunization antibodies to dextran were only of the other idiotype. The absence of cross-reactivity strongly suggests that the idiotypes of antidextran antibodies are directed against different epitopic groups on the antigen.

A large proportion (24-45%) of circulating lymphocytes of normal BALB/c mice was found to have surface immunoglobulins with polyclonal characteristics. Following implantation with plasmacytoma, the percentage of these normal receptor-carrying lymphocytes (RCL) was found to decrease. Concomitant with the growth of the tumors, the proportion of lymphocytes having receptors with the structural properties of the specific plasmacytoma globulin gradually increased. The antisera with which these new surface structures were demonstrated were specific for the variable portion of the Fab fragment, the idiotypic determinant of the plasmacytoma globulin. These antisera were not only raised in rabbits and rendered antiidiotypic by appropriate absorptions, but also in BALB/c mice. Evidence is presented that this alteration of receptors on the normal lymphocytes depends on the presence of tumor cells and is not caused by nonspecific absorption of the immunoglobulins to the lymphocytes.

Circulating lymphocytes of plasmacytoma-carrying BALB/c mice were found to lose their normal surface immunoglobulins; in their place surface structures characteristic of the specific plasmacytoma globulin were demonstrated by the immunocytoadhesion technique. These changes were experimentally reproduced by the incubation of normal BALB/c lymphocytes with an RNA preparation obtained by hot phenol extraction from the excised plasmacytomas. RNA treated by RNAse was inactive, while DNAse or trypsin had no inactivating effect. Lymphocytes, killed with heat or KCN, underwent no alteration of surface receptors following incubation with the tumor RNA. Plasmacytoma RNA, injected intraperitoneally into normal mice, also altered the reactivity of circulating lymphocytes. These observations suggest the possibility that this effect contributes to the functional impairment of the immune system in this disease.

The secretion of the antidiuretic hormone, arginine vasopressin, has been studied in a patient who developed peripheral neuropathy and the syndrome of inappropriate antidiuresis during therapy with vincristine sulfate. The patient's plasma arginine vasopressin concentration, determined by a radioimmunoassay technique, was markedly increased despite profound hyponatremia and rose even higher following correction of the electrolyte imbalance. In six other vincristine-treated patients, in whom neither neuropathy nor inappropriate antidiuresis was observed, plasma arginine vasopressin concentration was in the normal range. These findings indicate that the inappropriate antidiuresis, which can occur during vincristine therapy, is associated with an abnormal increase in arginine vasopressin secretion. This complication appears to be related to the other neurotoxic effects of the drug and may be due to an alteration in the normal osmoreceptor control of vasopressin secretion.

Waldenström's macroglobulinemia is an immunoproliferative disorder characterized by the presence of large amounts of monoclonal macroglobulin (IgM) in the serum, apparently produced by abnormally proliferating lymphocytes.1 While in the original description of Waldenström the number of lymphocytes was not increased in the peripheral blood, the bone marrow showed characteristic lymphocytic infiltrations and in later reports on macroglobulinemia the disease was associated with peripheral lymphocytosis.2 Thus, macroglobulinemia has variable morphologic manifestations.IgM consists of five subunits which have the general structure of all immunoglobulins, namely a pair of type specific heavy chains and a pair of light chains of either the κ type or the λ type. Five such subunits combine to form an IgM molecule (μ2 κ2)5 or (μ2 λ2)5. In 20% to 30% of the patients Bence Jones protein is also present.3 Most patients also have traces of uncombined subunits (IgMs), but free μ chains in this disease have not

The biochemical defect in thalassemia is thought to consist of a diminished capacity of the erythropoietic cells to synthesize one of the polypeptide chains of hemoglobin. Thus, the common variants of this disease have been designated as αand β-thalassemia. β-Thalassemia is usually associated with a twofold increased proportion of hemoglobin A2 and a slight elevation of fetal hemoglobin (hemoglobin F) in hemolysates, but many families have been described in which the hemoglobin abnormality is characterized by low or normal levels of hemoglobin A2 and high concentrations of hemoglobin F (10% to 30%). This variant of the disease has been designated as F-thalassemia or βδ-thalassemia since the synthesis of both β- and δ-chains appears to be impaired. The distribution of hemoglobin F in the erythrocyte population is uneven in contrast to the hereditary persistence of fetal hemoglobin (HPFH) in which all erythrocytes appear to have the same concentration of hemoglobin