Mark H. Kaplan

Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine

BACKGROUND Infection with the human T-cell lymphotropic virus type I, a retrovirus, can cause a distinctive cancer, adult T-cell leukemia-lymphoma. The median survival of patients with the acute and lymphomatous forms of the disease is short, despite the use of cytotoxic chemotherapy. METHODS We treated 19 patients with acute or lymphomatous forms of adult T-cell leukemia-lymphoma with oral zidovudine (200 mg five times daily) and interferon alfa (Intron A, 5 to 10 million units subcutaneously each day). Seven of these patients had either relapsed after multiagent cytotoxic chemotherapy or failed to respond to that treatment. RESULTS Major responses were achieved in 58 percent of the patients (11 of 19), including complete remission in 26 percent (5 of 19). Four patients in whom prior cytotoxic therapy had failed had major responses, two of which were complete remissions. Six patients have survived for more than 12 months, with the longest remission since the discontinuation of treatment lasting more than 59 months. CONCLUSIONS The combination of zidovudine and interferon alfa has activity against adult T-cell leukemia-lymphoma, even in patients in whom prior cytotoxic therapy has failed. This regimen should be evaluated further for its role in the treatment of adult T-cell leukemia-lymphoma.

Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS)

We present a review of the spectrum of human T-lymphotropic virus type III (HTLV-III) infection with particular emphasis on cutaneous manifestations in 217 patients. Correlations are made with immunodeficiency as measured by absolute T-helper cell number. A classification is presented of these dermatologic findings.

Bacteremia and fungemia complicating neoplastic disease: A study of 364 Cases

During a 14 month period there were 364 episodes of bacteremia and fungemia at Memorial Sloan-Kettering Cancer Center. The first nine months of the study were retrospective, and the next five prospective. In patients with leukemia or lymphoma (group 1), Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus were the most frequently isolated organisms. The mortality in this group was 40.5 per cent. In the patients with solid tumor (group 2), Esch. coli, Staph. aureus, Bacteroides sp. and Candida sp. were most frequent. Mortality was 27.8 per cent. The source of infection in both groups was often indeterminate. High mortality was associated with pulmonary and intraabdominal infection and with Ps. aeruginosa, K. pneumoniae or polymicrobic sepsis. Factors of prognostic significance were the causative microorganism, source of infection and shock. Although mortality was higher in patients with leukopenia than in those with normal leukocyte counts, the differences were not significant. The mortality in this series was low considering the severity of the underlying diseases and the immunosuppressed state of many of the patients. In a prospective, randomly controlled study, mortality was further diminished by infectious disease consultation at the time the positive blood culture was reported. Severe fungal superinfection, predominantly aspergillosis and candidiasis, was found in 52 per cent of the autopsy patients with leukemia or lymphoma (group 1), but in only 8 per cent of those with solid tumors (group 2).

Theory and Measurements of the Glass‐Transformation Interval of Polystyrene

Equations for the apparent heat capacity in the glass‐transition interval as functions of temperature, heating rate, and thermal history have been developed and programmed for computation. The hole theory of liquids was used as basis for the analysis of the glass transition. Experimental information was derived from dynamic differential thermal analysis, DDTA, on polystyrene.The maximum of the apparent heat capacities found experimentally agrees with the theory. The peak temperatures Tm can be expressed over four decades of heating rates by logq = A′ − B/Tm, where q is the heating rate, A′ is an approximate constant, and B is the activation energy for hole formation. Higher cooling rates lead to higher activation energies on subsequent heating, indicating the need to recognize a hole size distribution.The minimum in the heat capacity that precedes the maximum on heating through the glass‐transition interval could be detected on quenched samples. Mathematical expressions for the minimum temperature and mag...

Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposis sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposis sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposis sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.

Cryptococcosis in a cancer hospital. Clinical and pathological correlates in forty‐six patients

The clinical and pathological findings in 46 patients with cryptococcosis at Memorial Sloan‐Kettering Cancer Center from 1956 to 1972 are reported. The striking predilection for cryptococcal infection in patients with leukemias and lymphomas is again confirmed. Of 41 patients with neoplastic disease, those with chronic lymphatic leukemia (CLL), Hodgkins Disease, chronic myelogenous leukemia (CML), myeloma and lymphosarcoma had the highest incidence of cryptococcosis. In all cases, neoplastic disease was widespread when infection occurred. All of these patients had leukopenia and absolute lymphopenia at the time of infection. Thirty‐nine were on steroids. Thirty‐one patients with neoplastic disease had disseminated infection. Review of pathology revealed a spectrum of inflammatory lesions. Histiocytic‐lymphocytic infiltrates occurred in the central nervous system in 10 patients. In six cases, reaction was granulomatous. There were single instances of suppurative and fibrotic reactions. Mortality from infection was high in patients with neoplastic disease. Twenty‐four of 28 deaths occurred within 60 days as a result of infection. Within one year, 10 more patients died, nine of cryptococcosis. Only three survived more than one year, and all patients died within 600 days. Twenty‐nine patients with neoplastic disease received amphotericin B. Only nine survived more than 60 days.

Isolation and characterization of the Lyme disease spirochete from the skin of patients with erythema chronicum migrans

The Lyme disease spirochete, which had previously been isolated with difficulty from human skin lesions of erythema chronicum migrans of Lyme disease, was grown from six of fourteen skin biopsies cultured in a newly modified Kellys medium. In two instances the Lyme disease spirochetes that were grown were also seen in histopathologic sections. Organisms grew in clumps in liquid culture medium. All six isolates reacted with a monoclonal antibody to a 31,000-dalton outer membrane protein. Only three of six reacted to a monoclonal antibody to a 34,000-dalton outer membrane protein, suggesting that different subtypes of this organism may infect man. Penicillin, erythromycin, and minocycline were bactericidal agents to all six spirochetes. These in vitro findings may be helpful in determining specific antibiotic treatment of Lyme disease, which was previously based primarily on clinical observations.

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis

BACKGROUND Secondary hyperparathyroidism is observed in patients with early chronic kidney disease (CKD). This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis. STUDY DESIGN Double-blind, randomized, 32-week, phase 3 study. SETTING & PARTICIPANTS 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries. INTERVENTIONS Cinacalcet:placebo (3:1 ratio). OUTCOMES & MEASUREMENTS Proportion of participants with a mean decrease of 30% or greater in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage of iPTH change from baseline, all during the efficacy-assessment phase. RESULTS A greater proportion of cinacalcet than placebo participants achieved a 30% or greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a 43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1% increase (placebo). At week 32, serum calcium levels were 8.9 +/- 0.8 mg/dL (-8.9%; cinacalcet) and 9.9 +/- 0.6 mg/dL (+0.8%; placebo), phosphorus levels were 4.5 +/- 1.0 mg/dL (+21.4%) and 4.0 +/- 0.7 mg/dL (+6.8%), and calcium-phosphorus product values were 40.1 +/- 8.3 mg(2)/dL(2) (+18.9%) and 38.9 +/- 6.9 mg(2)/dL(2) (+17.1%), respectively. During the study course, 62% (cinacalcet) and 1% (placebo) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences. Treatment generally was well tolerated, and most adverse events were mild to moderate in severity. LIMITATIONS The study was not designed to assess the effects of cinacalcet on vascular calcification, bone histomorphometric parameters, or other clinical outcomes. It is not known whether the observed differences in changes in iPTH levels are clinically more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders. CONCLUSIONS These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels.

Papulosquamous dermatoses of AIDS

We review the spectrum of papulosquamous disorders in the setting of infection with the human immunodeficiency virus (HIV). Included is a discussion of xerosis generalisata, seborrheic dermatitis, psoriasis, pityriasis rosea-like eruption, keratoderma blennorrhagicum, acquired ichthyosis, and erythroderma. Mechanisms of pathogenesis, including possible common pathways and relationships to underlying immunosuppression, are emphasized.

Cutaneous nocardiosis: Case reports and review

Two cases of cutaneous nocardial infection are reported. The Nocardia species are gram-positive, partially acid-fast bacteria. Cutaneous involvement may develop as one of four types: (1) mycetoma, (2) lymphocutaneous (sporotrichoid) infection, (3) superficial skin infection, or (4) systemic disease with cutaneous involvement. A review of each of these types of infection is included, as well as potential clues that may suggest the diagnosis of nocardiosis.