S. Benham Kahn

Unmet psychological, social, and economic needs of persons with cancer in pennsylvania

Six hundred twenty‐nine persons with cancer (PWC) selected from the Pennsylvania Cancer Registry plus 397 nonprofessional (support) persons involved in their care (SP) were interviewed to determine their views of the unmet psychological, social and economic needs of PWC. The most frequently mentioned unmet need was for help in dealing with emotional problems (estimated at 25% of PWC state‐wide). Other unmet need estimates ranged from 14% for financial to 4% for transportation, with 59% of PWC reporting at least one unmet need. Characteristics of PWC reporting unmet needs included being younger, a history of emotional problems, a chronic illness in addition to cancer, more advanced stage at diagnosis, and a diagnosis of lung cancer. The percent of PWC and CP reporting unmet needs were very similar. These findings indicate that more effective screening for psychosocial problems and referral to supportive services is needed.

Unmet needs of persons with cancer in pennsylvania during the period of terminal care

A stratified random sample of recent cancer deaths was drawn from the Pennsylvania death registry, and 433 family members or close friends were interviewed concerning unmet needs during the last month of life. It was estimated that 72% of persons who died of cancer in Pennsylvania experienced at least one unmet service need during this period. The most frequently reported was help with activities of daily living, estimated at 42% of cancer deaths, involving over 11,000 persons each year in the state. There were significantly more unmet needs during the terminal period, compared with just after diagnosis, in activities of daily living, obtaining health care, transportation, and problems with medical staff. Our findings indicate a need to increase a broad range of support programs during the terminal period, especially of home‐care services.

Effects of trimethoprim on folate metabolism in man

Recent studies have demonstrated a synergistic effect of dihydrofolate reductase (DHFR) inhibitors and sulfonamides in the therapy of chronic urinary tract infections and malaria. Trimethoprim (TMP) (Ro‐56846, Hoffmann‐LaRoche) has 10,000 times more inhibitory effect on bacterial DHFR than on mammalian DHFR. Folate metabolism was evaluated in 10 normal patients treated with TMP alone for 4 weeks and 14 patients with chronic genitourinary infections treated with TMP and sulfonamides for periods up to 2 years. Parameters under study were complete blood count, bone marrow examination, serum and red blood cell folate levels, formiminoglutamic acid (FiGlu) excretion, and lobe counts of circulating neutrophiles. In order to measure folate activity a mutant strain of L. casei resistant to TMP was developed (Hitchings and Burchall, Burroughs Wellcome & Co. [U.S.A.] Inc.). In the short‐term group 1 patient developed thrombocytopenia and another anemia associated with transitional megaloblastosis, while 5 patients excreted FiGlu and all had significant elevation of lobe counts. When the drug was stopped these abnormalities disappeared in 2 weeks. One patient ingesting the combination of drugs demonstrated thrombocytopenia and leukopenia which disappeared when citrovorum factor was given despite continued administration of drugs. The dose of citrovorum factor needed to ensure hematologic normalcy was 400 µg. It is concluded that TMP has mild inhibitory effects On folate metabolism in man at the tissue level which can be overcome by administration of reduced folates.

Disseminated intravascular coagulation—a complication of chemotherapy in acute myelomonocytic leukemia

This is the first reported case of disseminated intravascular coagulation (DIC) occurring as a complication of chemotherapy in acute myelomonocytic leukemia. The DIC was successfully treated with heparin. Chemotherapy was continued, and a complete objective hematologic remission was obtained.

Simultaneous Fibrinogen and Platelet’ Survival with [75Se]Selenomethionine in Man

Summary. Simultaneous fibrinogen and platelet survivals were determined with a cohort label, [75Se]selenomethionine, in patients with hepatocellular disease and abnormal serial thrombin times (STT) and in control patients. The fibrinogen survival curves were divided into an anabolic and catabolic phase. In a control group maximum labelling of fibrinogen (anabolic phase) occurred within 24 hr and mean fibrinogen survival (catabolic phase) was 7.8 ± 2.8 days. Patients with hepatocellular disease fell into two groups, those with short fibrinogen survivals and those with normal fibrinogen survivals. In general, the more abnormal the STT the shorter the fibrinogen survival. The anabolic phase of the curve was also abnormal in that there was delay in incorporation of label in these patients.

Platelet and fibrinogen kinetics in the chronic myeloproliferative disorders

Simultaneous platelet and fibrinogen survival kinetic studies utilizing 75Seselenomethionine was performed on six patients with chronic myelogenous leukemia (CML), four with polycythemia vera (PV), one with idiopathic thrombocytosis (IT), and seven with myelofibrosis and myeloid metaplasia (MMM). The data revealed that platelet survivals, as well as fibrinogen survivals, were increased in CML as compared to patients with the other myeloproliferative disorders (MPD). Platelet survival was shortened in the patients with MPD as compared to the control patients. Thrombotic episodes were noted in three patients with MPD, while another had recurrent rectal bleeding. In all of these patients, platelet turnover was increased and was the only consistent determinant of hemostatic abnormality. Platelet adhesiveness and aggregation studies were inconsistently altered in any group and were not useful predictors of the risk of hemorrhagic or thrombotic diathesis. The data suggest that the platelets produced by patients with CML are functionally abnormal and underutilized when compared to control patients and to patients with other MPD. The thrombocytosis of CML results from decreased platelet utilization rather than from overproduction. Overutilization of platelets in patients with other MPD contributes to the thrombotic tendency noted in these patients. These results suggest another distinctive feature which separates CML from the other MPD. Platelet and fibrinogen kinetic studies are important in evaluating the pathophysiology of the thrombocytopenia or thrombocytosis of the myeloproliferative diseases as well as in investigating the physiology of hemostasis.

Myeloproliferative disorders: II CML: Clonal evolution and its role in management

Abstract Twenty-three patients with an established diagnosis of Ph 1 positive chronic myelogenous leukemia have been entered into an experimental study to determine the effect on survival of splenectomy and intensive cycle-active chemotherapy based on serial cytogenetic monitoring. Initially, all patients were induced into hematologic remission with busulfan, splenectomized and treated with cytosine arabinoside and 6-thioguanine. Chemotherapy was modified or intensified when abnormal chromosomal patterns were observed in dividing bone marrow cells or non-stimulated short term blood cultures. Elimination or reduction of the abnormal clones was correlated with improved clinical status in the experimental group. Most of the patients who developed abnormal clones prior to clinical evidence of transformation either lost the clone or showed a marked reduction in the size of the clone after aggressive therapy was instituted. The results suggest that survival was prolonged in this group of patients (4–133 months) when compared to historical controls. Pre-selection of patients in the series does not appear to explain the data since 20 of the 23 patients presented with at least one of the poor prognostic factors described by Jacquillat et al. [28] and over 60% of them had two or more of the unfavorable signs at diagnosis.

Platelet and Fibrinogen Kinetics with [75Se]-Selenomethionine in Patients with Myeloproliferative Disorders

Summary: Simultaneous platelet and fibrinogen kinetics were determined with a cohort label, [75Se]selenomethionine, in three patients with chronic myelocytic leukaemia (CML), three with subacute myelogenous leukaemia (SML) and three with myelofibrosis with myeloid metaplasia (MF). In the CML group platelet survival was normal to increased (10.5–14.0 days), platelet turnover was essentially within the control range (22 000–51 000 platelets/μ/day), fibrinogen survival was prolonged (11.0–19.0 days) and fibrinogen turnover decreased (0.12–0.32 mg/ml/day). In two patients with MF platelet survival was decreased (5.0–7.5 days) and platelet turnover sharply increased (215 000–385 000 platelet/μl/day): one of these patients had multiple thrombotic episodes with an associated decrease in fibrinogen survival (4.0 days) and increased fibrinogen turnover (0.85 mg/ml/day): the other patient had no haemorrhagic or thrombotic episodes and his fibrinogen survival and turnover were within normal limits. Four patients, three with SML and one with MF, presented with thrombocytopenia. Kinetic studies were performed to aid in selecting those patients that might benefit from splenectomy. Splenectomy was performed in two with excellent results. Platelet and fibrinogen kinetics are important adjuncts to the study of the pathogenesis, differential diagnosis, and therapy of the myeloproliferative disorders.

Polycythaemia Vera: Differential Diagnosis by Ferrokinetic Studies and Treatment with Busulphan (Myleran*)

Summary. Twenty‐two patients with polycythaemia Vera, six with benign polycythaemia or relative polycythaemia and six with secondary (hypoxaemic) polycythaemia were compared by means of ferrokinetic studies and measurement of bone‐marrow iron stores. In polycythaemia Vera a poor correlation was noted between the haemoglobin (Hb), packed cell volume (PCV) and total red‐cell mass (TRBC). Reliance on the Hb and PCV alone is frequently misleading in the differential diagnosis of the polycythaemic states. A rapid 59Fe T1/2 (< 30 minutes) was found in 85 per cent of patients with polycythaemia Vera, and was associated with absent marrow iron stores in 21 of 22 patients. In benign polycythaemia and relative polycythaemia the 59Fe T1/2 was normal and stainable iron was present in the marrow. Similar findings were noted in secondary polycythaemia.

Fibrinogen Survival with [75Se]Selenomethionine during l‐Asparaginase Therapy

Summary. Fibrinogen anabolism and catabolism in four patients (acute lymphoblastic leukaemia; lymphosarcoma cell leukaemia; generalized lymphosarcoma; hypernephroma) were determined with [75Se]selenomethionine during a period of hypofibrinogenaemia induced by l‐asparaginase. The anabolic phase was normal but the fibrinogen survival decreased to 1.5–4.0 days (normal range, 7.8 ± 2.8 days). Heparin therapy did not affect either the fibrinogen levels or abnormal thrombin times. In two patients with widespread Hodgkins disease in whom l‐asparaginase therapy was started after the labelling of fibrinogen with [75Se]selenomethionine, the fibrinogen survival was normal. The results suggest the production of an intrinsically abnormal fibrinogen with a decreased survival during l‐asparaginase administration.