Gerald L. Messerschmidt

Treatment of poor prognosis nonseminomatous testicular cancer with a “high‐dose” platinum combination chemotherapy regimen

A new intensive four drug combination chemotherapy regimen, termed PVeBV, consisting of cis‐platinum, vinblastine, bleomycin, and VP‐16, was administered to six previously untreated patients with poor prognosis advanced nonseminomatous testicular cancer and to four patients who had relapsed on primary platinum based regimens. The cis‐platinum was administered in 250 ml of 3% saline at twice the dose (40 mg/m2 IV days 1–5 every three weeks) used in other treatment schedules. All six previously untreated patients achieved a complete remission. Four achieved a complete remission with three cycles of PVeBV while the other two patients achieved a complete remission with an additional cycle of cisplatinum and VP‐16 at 200 mg/m2 IV × five followed by autologous bone marrow infusion. All four relapsed patients responded to PVeBV (two complete remissions and two partial remissions). There were no deaths associated with PVeBV therapy; however, myelosuppression was severe. There has been no renal toxicity (other than hypomagnesemia) observed with 35 cycles of high‐dose platinum therapy in previously untreated patients. These results indicate that PVeBV is a promising chemotherapy regimen for the treatment of poor prognosis testicular cancer patients. Furthermore, it appears that cis‐platinum can be administered at higher doses than previously used without an increase in renal toxicity if administered in hypertonic saline. The high‐dose cis‐platinum schedule, as used in PVeBV, warrants evaluation in other tumors which respond to standard‐dose platinum therapy.

Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma

Background. Chemotherapy‐associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C‐TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2–10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions.

Acute neurologic dysfunction after high‐dose etoposide therapy for malignant glioma

Etopside (VP‐16–213) has been used in the treatment of many solid tumors and hematologic malignancies. When used in high doses and in conjunction with autologous bone marrow transplantation, this agent has activity against several treatment‐resistant cancers including malignant glioma. In six of eight patients (75%) who we treated for recurrent or resistant glioma, sudden severe neurologic deterioration occurred. This developed a median of 9 days after initiation of high‐dose etoposide therapy. Significant clinical manifestations have included confusion, papilledema, somnolence, exacerbation of motor deficits, and sharp increase in seizure activity. These abnormalities resolved rapidly after initiation of high‐dose intravenous dexamethasone therapy. In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high‐dose etoposide therapy for malignant glioma.

Recurrent hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in Hodgkin's disease.

Hypercalcemia has been infrequently associated with Hodgkins disease. When seen, most cases have been attributable to skeletal invasion by disease. Herein is described a 40-year-old man with a 15-year history of Hodgkins disease. Each of four disease recurrences was heralded by hypercalcemia occurring in the absence of bone disease or elevation of parathyroid hormone levels. Marked elevations of 1,25-dihydroxyvitamin D levels were observed that paralleled his disease course and response to therapy. The repetitive association of hypercalcemia with an elevation of 1,25-dihydroxyvitamin D in this case provides further evidence of lymphoma-associated production of this vitamin.

T cell depletion of human bone marrow using monoclonal antibody and complement-mediated lysis

Human bone marrow was harvested from surgically resected bones of 25 patients and was tested for the presence of mature T cells. An average of 6.5% (±1.2% SE) of nucleated bone marrow cells formed spontaneous rosettes with sheep red blood cells. Functional T cells in bone marrow were also identified by characteristic responses to alloantigens and the T cell mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). The ability of three monoclonal antibodies (OKT.3, Lyt-3, and (Leu-1) to lyse peripheral T cells in the presence of rabbit complement was examined. All three reagents were found to be specifically lytic for mature T cells in peripheral blood. One reagent (Leu-1) was selected for use in depletion of T cells in human bone marrow. Seven of 10 experiments performed showed sufficient T cell responses to be evaluable. In all of these experiments, a marked reduction of T cells and T cell functions was observed. On the average, E rosettes were reduced 89.2% (±3.0% SE) below medium controls while the mean PHA, Con A, and mixed lymphocyte culture (MLC) activity were completely eliminated to levels below background. In four experiments, colony-forming units (CFU-GM) in bone marrow were assayed following treatment with Leu-1 and showed a mean increase of 194% (±32% SE) over medium controls. Since mature T cells are thought to be responsible for graft-versus-host disease in allogeneic bone marrow transplantation, this method of T cell depletion may be useful for preparing marrow for human bone marrow transplants.

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Drainage of Recurrent Pleural Effusion Via an Implanted Port and Intrapleural Catheter

Excerpt Pleural effusions associated with malignancy are a common problem encountered in clinical practice. Generally, 85% of these effusions are controlled by tube thoracostomy drainage and intrap...

Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia.

Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long‐term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. Care must be exercised in associating previous therapy and a subsequent malignancy. “Naturally” occurring second cancers must be separated from those which are iatrogenic. Associations in the literature have been made involving malignancies as a sequelae of prior gynecologic therapy. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. Irradiation therapy, however, has not yet been shown to be related to leukemia in cervical cancer patients. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified.