Reevaluation of the maximum tolerated dose of continuous venous infusion of 5-fluorouracil with pharmacokinetics.

5-Fluorouracil (5-FU) was administered as a continuous ambulatory venous infusion to 25 patients in a Phase I trial. The principal dose limiting toxic effect observed was mucositis. Skin rash and diarrhea occurred less frequently. Hematological toxicity was modest, and no hepatic toxicity was seen. One partial remission of 138 days duration was seen in a patient with metastatic breast carcinoma who was previously refractory to a 5-FU combination regimen. Patient tolerance of 5-FU delivered in this manner appeared highly variable. On the basis of this trial, we recommend that future studies evaluating the efficacy of long-term venous infusion of 5-FU should utilize a dosage of 450 mg/m2/day.

A randomized phase I and II study of short-term infusion of high-dose fluorouracil with or without N-(phosphonacetyl)-L-aspartic acid in patients with advanced pancreatic and colorectal cancers.

Fifty-two patients with advanced gastrointestinal (GI) malignancies who had not received previous chemotherapy or radiation therapy were randomized to be treated either with 24-hour infusion of weekly fluorouracil (5-FU) or the same plus N-(phosphonacetyl)-L-aspartic acid (PALA). Forty-seven patients were evaluable for the assessment of toxicity and antitumor activity. PALA was administered as an intravenous (IV) bolus over 15 minutes at a fixed dose, 250 mg/m2. The latter agent was administered 24 hours before the start of 5-FU infusion. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 3,400 mg/m2. In both arms of the randomized study, the courses were repeated every week. In both arms of the study, ataxia and myelosuppression were the dose-limiting toxic effects. At 5-FU dose of 3,400 mg/m2, one patient in each arm developed grade 3 hematologic toxicity. Other reversible side effects included grade 2 skin changes, nausea, and vomiting. During the administration of 2,600 mg/m2 of 5-FU over 24 hours, the steady state plasma 5-FU concentration was approximately 20 mumol/L. The maximum tolerated dose (MTD) for 5-FU for protracted treatment is 2,600 mg/m2 in either arm of the study. Therapeutic response was predominantly seen in the combination arm: there were two patients with complete response (CR) and 11 patients with partial response (PR) of 28 patients in the study. In the 5-FU alone arm there were four PR and 19 patients in the study.

Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment.

A randomized, controlled trial was initiated in 1977 to evaluate the impact of three alternative approaches to consolidation and maintenance therapy after initial maximal response for multiple myeloma. All patients were treated initially with BCNU, cyclophosphamide, and prednisone (BCP) until a designated level of response was achieved. Responders were randomly assigned to either melphalan and prednisone (MP); prednisone, Adriamycin (Adria Laboratories, Columbus, Ohio), azathioprine, and vincristine (PAIV), or no therapy until relapse, then treatment with BCP. Initial response rates were comparable with previous trials. A small number of incremental responses were observed with both MP and PAIV. Survival was the same for all three maintenance approaches and the same as that observed in our previous continuous BCP or MP therapy. Additional or consolidation/maintenance therapy of the type administered here appears to offer little advantage once an initial response has been achieved.

Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial.

A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were randomly assigned treatment with cyclophosphamide, vincristine, and prednisone plus BCNU (BCOP) or doxorubicin (CHOP). In diffuse histiocytic (DH) lymphoma, CHOP produced superior complete (54% v 34%) and total (70% v 46%) response rates. Among the responders to either therapy, no differences were seen in duration of response or survival times. Median duration of response has not been reached with follow-up in excess of 50 months. In categories of lymphoma other than DH (including small-cell, mixed, and nodular histiocytic lymphomas), complete (27% v 29%) and total (48% v 54%) responses were similar for BCOP and CHOP, as were durations of response and survival. These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas. CHOP appears preferable for diffuse large-cell categories, since it resulted in greater overall survival in patients with DH lymphoma; this was due to a significantly greater response rate, since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders.

Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program.

PURPOSE: A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy. METHODS AND MATERIALS: Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy. RESULTS: Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months. CONCLUSION: This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial.

Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report.

A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4,000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completely evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation (P = .05). In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks (P = .12). Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P = .06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax. Disease-free survival is enhanced in the patients receiving thoracic irradiation. More effective chemotherapy is critically needed to significantly improve overall survival. These preliminary results suggest that thoracic irradiation should be a primary component in the therapy of these patients, although this combined therapy is moderately toxic.(ABSTRACT TRUNCATED AT 400 WORDS)

Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.

PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy.

PURPOSE: We have previously shown that relative thymidylate synthase (TS) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and cisplatin are inversely associated with response and survival. This is a presumed function of TS as a target for 5-FU activity. We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing (ERCC1) gene is inversely associated with response and survival as an independent function of cisplatin efficacy. PATIENTS AND METHODS: Patients had intact, untreated, primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the beta-actin gene. RESULTS: The median ERCC1 mRNA level from 38 primary gastric cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) also segregated responsive versus resistant tumors (P = .024). With both ERCC1 and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) responded (P = .003). CONCLUSION: Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC1 mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined.

Splenectomy for Felty's syndrome. Clinicopathological study of 27 patients.

The major clinical and pathological features and the long-term follow-up of 27 patients with Felty's syndrome who were treated with splenectomy for sever granulocytpenia and for acute, chronic, or recurrent infection were studied. Granulocyte counts rose within days in most patients, although slow responses and transient granulocytopenia did occur; only 12% of the patients had persistent or recurrent granulocytopenia. Infections resolved promptly in 77% of the patients, more slowly in the remainder, and only one patient had new problems of infection after aplenectomy. Splenic enlargement, present in all but one case, was attributable to expansion of the sinusoidal pulp. The most substantial pathological features of immune stimulation included germinal center hyperplasia and prominent clusters of plasma and preplasma cells within sinuses.

Treatment of isolated systolic hypertension with labetalol in the elderly.

Antihypertensive therapy with labetalol was evaluated in a prospective, randomized, multicenter, double-blind study of 133 elderly patients with isolated systolic hypertension (standing systolic blood pressure [BP] greater than or equal to 160 mm Hg; diastolic BP less than 95 mm Hg). Following a placebo-washout period, patients received either labetalol (n = 70) or placebo (n = 63), which was titrated as necessary from 100 to 400 mg twice a day over a 6-week period. Once the BP was controlled (standing systolic BP less than 160 mm Hg, and greater than or equal to 10-mm Hg decrease from baseline) or the maximum dosage had been given, patients continued receiving the same regimen until the end of the titration period and throughout a 4-week maintenance period. Blood pressure was controlled in 57 (81%) of 70 of the labetalol-treated patients (86% receiving less than or equal to 200 mg twice a day) compared with 34 (54%) of 63 of the placebo-treated patients. Throughout the active treatment periods, BP was significantly lower in patients treated with labetalol compared with those taking placebo; mean standing systolic BP decreased 26 mm Hg in the labetalol group vs 9 mm Hg in the placebo group. Side effects were generally mild, and the dropout rates due to adverse experiences were similar between treatment groups (14% in the labetalol group vs 10% in the placebo group). In summary, labetalol can effectively lower systolic BP in the elderly without causing adverse orthostatic changes.

Autologous marrow transplantation for patients with acute myelogenous leukemia--a preliminary report.

Twelve consecutive adult patients with acute myelogenous leukemia have been entered on a treatment protocol which examines the role of "remission-intensification" during maintenance using high-dose chemoradiotherapy and autologous remission marrow transplantation. Nine patients have achieved complete remission: 5/9 patients have had remission marrow stored followed by high-dose chemoradiotherapy and autologous marrow transfusion; two patients were removed from study because of excessive toxicity during remission-induction precluding high-dose therapy; two patients are currently ready for marrow storage; and two patients are receiving remission-induction therapy. Of the five transplanted patients, four experienced excellent return of blood counts and one patient has had prolonged pancytopenia and continues to require red cell and platelet transfusions. There have been no serious infectious or hemorrhagic problems associated with post-transplant period in any of the patients. Autologous remission bone marrow transplantation following lethal high-dose chemoradiotherapy results in effective restoration of normal hemopoiesis, is associated with acceptable toxicity and may be an effective means of increasing the numbers of acute leukemia patients having long-term complete remission.

Clinical and metabolic responses to parenteral nutrition in acute renal failure. A controlled double-blind study.

1. Thirty patients with acute renal failure who were unable to eat adequately were evaluated while they received parenteral nutrition with glucose alone (n = 7), glucose and 21 g/day essential amino acids (EAA, n = 11) or glucose, 21 g/day essential and 21 g/day nonessential amino acids (ENAA, n = 12). Energy intake did not differ with the three treatments. Patients were studied in a prospective double blind fashion. 2. Thirteen patients recovered renal function and 11 survived to leave the hospital. Those in whom renal failure was attributed to hypotension and/or sepsis had a poorer recovery of renal function (17%) and survival (17%). Recovery of renal function and survival was greater in patients on the medical service as compared to the surgical service and in those who received more energy. Recovery of renal function was worse in those treated with dialysis. There were no differences in recovery of renal function of survival among the three treatment groups. 3. Many patients were markedly catabolic as indicated by nitrogen balances, urea in nitrogen appearance rates (UNA), serum protein concentrations, and plasma amino acid levels. There was no correlation between the degree of catabolism and recovery of renal function or survival. Mean UNA in individual patients also correlated with body weight. Among the three groups, however, UNA was significantly less with the group receiving EAA as compared to ENAA. 4. Serum protein concentrations were lower than normal in all treatment groups. Serum albumin fell significantly during the treatment in the more catabolic patients. Plasma amino acid levels tended to fall in all three groups and concentrations at the end of the treatment were frequently lower than normal. 5. These data suggest that acute renal failure patients who are unable to eat adequately are often hypercatabolic and have a high mortality, particularly if hypotension or sepsis is the cause of renal failure. The improved survival in those with higher energy intakes, the high rate of net protein breakdown, the low serum protein levels and the reduced plasma concentrations of both essential and nonessential amino acids suggest that greater quantities of energy and both essential and nonessential amino acids may be beneficial to such patients.

Quantitation of intratumoral thymidylate synthase expression predicts for resistance to protracted infusion of 5-fluorouracil and weekly leucovorin in disseminated colorectal cancers: preliminary report from an ongoing trial.

A clinical trial for patients with measurable, disseminated colorectal cancer is being conducted to determine: (1) if intratumoral expression of thymidylate synthase (TS) affects response to protracted-infusion 5-fluorouracil (5FU); and (2) whether intratumoral expression of TS increases when clinical resistance is found after response to 5-FU. Polymerase chain reaction technology is employed to determine TS expression. Using beta-actin as an internal standard, TS expressions for 26 patients range from 0.5 x 10(-3) to 22.6 x 10(-3). Currently, 22 patients are evaluable for response and TS quantitation of their measurable tumour. 8 patients (36%) have had partial responses; 3 responding patients had been previously treated with 5-FU. A strong statistical association between TS expression and resistance to therapy has been found (P = 0.004). No patient with TS expression of 4.0 x 10(-3) or greater has responded. On average, patients previously treated with 5-FU have slightly higher levels of TS expression in their measurable tumours (P = 0.4). Whether responding patients will develop increased expressions of TS upon clinical progression of their cancer remains to be determined. Confirmation of these results in a larger cohort could lead to a scientific rationale for deciding upon specific therapy for patients with disseminated colorectal cancers.

Felty's syndrome without splenomegaly.

A woman with chronic rheumatoid arthritis and severe granulocytopenia but without splenic enlargement by physical examination or radionuclide scanning was studied for granulocyte-bound immunoglobulin G (IgG) and serum antigranulocyte antibodies. Prior to splenectomy 73 to 110 X 10(-14) g/cell of IgG were detected on the patient's granulocytes, a value in the range (20 to 220 X 10(-14) g) found in 16 patients with classic Felty's syndrome. Granulocyte-bound IgG in 21 patients with rheumatoid arthritis without Felty's syndrome was less than 20 X 10(-14) g. Following splenectomy, the patient had a partial correction of her peripheral granulocyte count, and granulocyte bound IgG was repeated less than 20 X 10(-14) g/cell. When paraformaldehyde-fixed granulocytes, obtained either from normal donors or from the patient after splenectomy, were incubated in the patient's serum obtained before splenectomy, more IgG was bound than with control serums from patients with rheumatoid arthritis. Similar results were obtained when serums from patients with classic Felty's syndrome were incubated with paraformaldehyde-fixed granulocytes. Thus, patients with rheumatoid arthritis without overt splenic enlargement may have pathophysiologic Felty's syndrome, and in vitro studies such as these may be used to define this process.

Comparison of labetalol and prazosin in hypertensive patients using automated ambulatory monitoring.

The differential effects of prazosin and labetalol on blood pressure and heart rate in the clinic and during daily activity were measured in a double-blind study utilizing automatic ambulatory monitors. One hundred five patients with essential hypertension (sitting diastolic blood pressure equal to 101 mm Hg) were randomly assigned to receive prazosin (n = 52) or labetalol (n = 53). Sixty-eight percent of labetalol-treated patients and 50 percent of prazosin-treated patients achieved blood pressure control during clinic visits (sitting diastolic blood pressure less than 90 mm Hg) and were subsequently monitored for 12 hours of normal daily activities. Ambulatory monitoring revealed labetalol-treated patients to have significantly greater decreases in systolic and diastolic blood pressures during daily activity than prazosin-treated patients. Heart rate and rate-pressure product were significantly reduced in the labetalol group but not in the prazosin group. It is concluded that the potential benefits of dual adrenergic blockade, not readily apparent in the non-stressful clinic environment, become more evident during the course of daily activities.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

The effect of hepatitis B antigenemia on long-term success and hepatic disease in renal transplant recipients.

The records of 192 cadaver renal allotransplants were reviewed in order to evaluate the role of the hepatitis B antigen (HBsAg) carrier state on graft function, patient survival, and the incidence of severe hepatic dysfunction. Twenty-one allografts were placed into patients with hepatitis B antigenemia. After follow-up ranging from 1.5 to 8 years (mean 4.7), graft and patient survivals were not statistically different from antigen-negative patients. In addition, the acquisition of HBsAg after grafting did not seem to affect the rate of graft failuue or death. Neither cirrhosis not fatal hepatic failure developed in the HBsAg carrier group, whereas five HBsAg-negative recipients died of hepatic disease. Among HBsAg-positive recipients, nine with functioning renal allografts and five with graft failures, there was a low incidence of e antigen, suggesting low infectivity. This may explain the lack of correlation of the surface antigen with serious liver disease. Severe hepatic disease developing in renal graft recipients is most likely attributable to causes other than hepatitis B infection. The presence of hepatitis B antigenemia alone should not be a deterrent to renal transplantation.

Antibody-dependent cell-mediated cytotoxicity tests for immunosuppression monitoring of transplant patients.

The antibody-dependent cell-mediated cytotoxicity (ADCC) effector activity and phytohemagglutinin (PHA) response of kidney transplant patients were monitored by a new whole blood microassay that permitted performance of 20 tests using only 1 ml of blood. Eleven patients were followed on as many as 55 different occasions with these tests. The ADCC activity of dialysis patients was essentially the same (78% chromium release as compared with 83% in normal controls). However, patients with kidney transplants undergoing immunosuppression had approximately one-half the chromium release (40%). Daily fluctuation in the chromium release could not be used as a predictor of subsequent rejection. The PHA response was as much as 50-fold less in the immunosuppressed patients. Both values also tended to be slightly higher among patients who were doing well than those who were doing poorly. This may reflect the need for greater immunosuppression in the rejecting patients.

Effects of age on responses to treatment and survival of patients with multiple myeloma.

The elderly patient with malignancy is often considered a poor risk for treatment. To assess the effect of age on the treatment of one such disease, multiple myeloma (a disease with increased incidence in the elderly), a study was made of 280 patients treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide and prednisone on a Southeastern Cancer Study Group protocol. Initial response rates after six months of treatment were equivalent for the older compared with the younger age groups, with a slightly longer remission duration for those over 70. Likewise, survival was equivalent for the older patients. This was not the result of selection of older patients with less advanced disease, since the proportion with both good and poor risk factors are not significantly different in the various age groups. Moreover, for patients with each of the prognostic factors, older patients responded at least as well as younger patients. There were no significant differences among the age groups in gastrointestinal, skin, hair, or hematologic toxicity, although there was a slightly higher incidence of mild granulocyte and platelet toxicity in patients over 60. These findings are in contrast to the widely held belief that older patients cannot tolerate chemotherapy. On the contrary, they suggest that the elderly patient with myeloma may be expected to respond and survive, without excessive toxicity, at least as well as a younger counterpart with similar prognostic factors.

Amyloidosis complicating hairy cell leukemia.

A patient development renal failure following a ten-year affliction with hairy cell leukemia. Renal biopsy showed amyloidosis, characterized by the presence of potassium permagnate-sensitive congophilia in deposits within glomeruli and renal blood vessels. Electron microscopy demonstrated amyloid fibrils. Immunohistochemical technics showed the deposits were composed of AA Protein. These Congo red staining properties, and the presence of AA Protein are characteristic of deposits in secondary amyloidosis. Secondary amyloidosis is a known complication of many chronic illnesses. This report shows it may concur with hairy cell leukemia, and that amyloidosis should be considered in the differential diagnosis of renal failure in patients with hairy cell leukemia.