Edwin C. Cadman

High dose cytosine arabinoside (HDARAC) in refractory acute leukemia.

Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara‐C) over 29 drug cycles. Drug infusions were spaced at 12‐hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2‐ to 30‐day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia.

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases.

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkins disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkins disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non‐lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkins disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkins disease to the diagnosis of leukemia is significantly shorter (p < .0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were treated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival (median one month).

Needle exchange decreases the prevalence of HIV-1 proviral DNA in returned syringes in New Haven, Connecticut

PURPOSE To report on the deployment of the syringe tracking and testing system in the New Haven needle exchange program, which is the first federally funded evaluation of a needle exchange program conducted in the United States. PATIENTS AND METHODS A legal needle exchange for intravenous drug users began in New Haven, Connecticut, in November 1990. All syringes distributed by the program received unique tracking codes. Syringes were tracked and HIV-1 proviral DNA prevalence in returned syringes was assessed using polymerase chain reaction and Southern blotting. RESULTS At the outset of the program, the prevalence of HIV-1 proviral DNA in syringes exceeded two thirds. Prevalence decreased rapidly to less than 45% during the first 3 months of the program and remained at this level for the following 10 months. During the periods of decreasing prevalence and subsequent steady state, no changes in the demographics of program participants or in the drug use habits of newly enrolling clients that could account for the decrease in HIV-1 prevalence in needles were detected. In addition, the program referred almost 20% of its clients to drug treatment programs. CONCLUSION The needle exchange program in New Haven has decreased the percentage of syringes testing positive for HIV-1 proviral DNA among needle exchange clients while simultaneously serving as an entry point for drug treatment.

Hyperphosphatemia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Burkitt cell leukemia

Hyperphosphatemia, hypocalcemia and acute oliguric renal failure resulting from uric acid nephropathy developed in a patient with Burkitts lymphoma and Burkitt cell leukemia after effective chemotherapy. A review of other reported cases in which the patients had similar metabolic abnormalities is presented, and the pathophysiology is discussed. The clinical setting in which these metabolic developments are most likely to occur is defined, and an approach for their prevention and management is presented.

Bone involvement in Hodgkin's disease

Eighteen patients with osseous involvement were identified from a series of 124 consecutive patients treated with combined‐modality therapy with advanced‐stage or relapsing Hodgkins disease. Multiple lesions were seen as frequently as were solitary lesions. Nodular sclerosing histology was as prevalent as mixed cellularity disease. However, those five cases initially diagnosed at protocol entry were predominantly mixed cellularity (80%) with multiple lesions (80%). Sites of involvement included: the spine, 24; pelvis, 8; ribs, 4; femur, 3; skull, 1; and shoulder 1. Actuarial survival for these patients was 84% at nine years. Only three patients were induction failures and no patient has had a relapse. Patients with bone lesions had favorable responses to combined‐modality therapy.

Curative potential of combined modality therapy for advanced Hodgkin's disease

During the period from 1969 through 1977, 124 patients with advanced Hodgkins disease underwent treatment with combination chemotherapy and radiotherapy. Sixty‐three cases were previously untreated, and 61 were relapses following radical radiotherapy for localized Hodgkins disease. No patient in this series had received prior chemotherapy. Of 102 patients (84%) who have entered complete remission, 92 remain in complete remission with a median follow up time of five years, 10 patients having relapsed, and acute leukemia having developed in 2. The cumulative survival rate for all 124 patients is 80% at five years; the relapse‐free survival rate is 74%. In many, if not most cases, the Hodgkins disease appears to be cured. We have also identified two subgroups of patients for whom the prognosis is worse than for patients with advanced‐stage disease as a whole. Patients over the age of 40 years have a five‐year survival rate of only 45%, compared with 89% for all other patients. Those Stage IV patients with multiple extranodal sites of involvement have a five‐year survival rate of 48%, compared with 81% for other Stage IV patients with only a single extranodal site involved.

Leptomeningeal mycosis fungoides.

Central nervous system involvement with mycosis fungoides complicated the clinical course of a patient at a time when his skin was clinically free of disease following systemic chemotherapy. A leptomeningeal syndrome of blurred vision and papilledema, and confusion progressing to coma, was associated with elevated spinal fluid pressure and abnormal spinal fluid cells morphologically similar to those seen in the Sézary syndrome. The symptoms were dramatically reversed by intrathecal methotrexate, brain irradiation, and steroids. Mycosis fungoides recurred in the skin, in the spinal fluid, and in both eyes. Despite continued systemic and intrathecal chemotherapy, the patient died from mycosis fungoides. This is the second patient reported with meningeal mycosis fungoides.

Sclerosing variants of follicular center cell lymphomas presenting in the retroperitoneum.

A study of 22 patients with sclerosing variants of follicular center cell lymphoma (FCCL) presenting as a retroperitoneal mass is reported. These FCCL variants comprise 74% of retroperitoneal non‐Hodgkins lymphoma presentations. A partial intranodal follicular growth pattern was present in each case, and marked sclerosis of a distinctive pattern was associated with extensive perinodal lymphomatous infiltration. Small cleaved cells (SCC) predominated in five cases, large cleaved cells (LCC) in 14, and large noncleaved cells (LNCC) in three. Eighty percent of patients with SCC predominance were Stage I‐II, compared to 50% of those with LCC predominance; all three LNCC cases were Stage IV. High stage was attained primarily by renal invasion or infiltration out the mesenteric root into gut or omentum; only three patients had biopsy proven extraabdominal disease. Combined modality therapy achieved an 88% complete or partial remission rate in patients with SCC and LCC predominance; all three LNCC patients died.

Biochemical Modulation as a Guide to Rational Combination Chemotherapy for the Treatment of Cancer

The treatment of cancer with drugs has led to significant improvement in response and survival of some patients with neoplastic disease. Unfortunately, the tumors which have benefited most from drug therapy account for a minority of the patients who have cancer. It is accepted from clinical trials that combinations of drugs generally lead to better results than that which follows treatment with only one drug. These drug combinations have often been chosen because of different proposed sites of drug action, different toxicity, or simply empirically without any logic. Seldom have drugs been combined in a sequential fashion dictated by the biochemical perturbations that result from the drugs to be used. A rational aproach to sequential drug therapy might allow for further improvement in the treatment of malignancy. If biochemical parameters could be identified which predict activation of a given drug or a given drug sequence, then perhaps characterization of cancer cells removed from the patient could be used to design the best possible therapy for that patient. Sequential use of certain drugs have been shown to be synergistic in their ability to inhibit animal tumors [1] and is not a new concept in the approach to improve cancer treatment. The interaction of drugs with either other drugs or natural metabolites has been an interest of many investigators [2–7].