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Natural killer (NK) cell numbers and T lymphocyte subpopulations in peripheral blood were evaluated in six patients with aplastic anemia (AA). The immunophenotyping results were correlated to in vitro tests of NK cell cytotoxicity against K562 cells and of immunoglobulin (Ig) production after pokeweed mitogen (PWM) stimulation. A significant decrease was found both in the percentage of Leu 11 positive cells and in NK cell activity as compared to age- and sex-matched healthy controls. The decrease in NK cell activity could not be entirely compensated by an increase in effector/target cell ratios, thus suggesting not only a quantitative but also a functional defect in NK cells of the AA patients. Three of four AA patients tested showed no major increase of Ig production after PWM stimulation. All these three patients also had fewer "functional T helper" cells (Leu3+/Leu8-) and increased numbers of T suppressor/cytotoxic cells (Leu2+) when compared to controls. No significant differences in numbers of B lymphocytes (B1+) could be found. Our findings suggest a possible linkage between quantitative and qualitative abnormalities in lymphocyte subsets in aplastic anemia. However, no evidence was found to support the hypothesis of increased NK cell activation behind the hemopoietic depression in this disease.

The possibilities were studied of achieving remission more quickly, of preventing conceivably alkylator-induced blastic transformation, and of prolonging survival in chronic myelocytic leukemia (CML) by replacing busulfan induction of remission by antimetabolite induction. The promise of the project was not considered to merit a prospective, controlled, randomized multicenter study, and therefore a retrospective, non-controlled, non-randomized pilot study was elected. One antimetabolite-treated group (cytosine arabinoside and thioguanine) and two busulfan-treated patient groups were studied. One of the latter two groups received splenic irradiation in addition to busulfan. No statistically significant differences between the busulfan groups were found in the time to achieve remission, the length of the first, unmaintained remission, the frequency of blastic metamorphosis or the cost of treatment. The actuarial survival curves of all three groups were similar. The antimetabolite induction was well tolerated and led to a statistically significantly more rapid remission than busulfan. However, the remission was significantly shorter, and no significant difference in the frequency of blastic metamorphosis was found between the groups. The median cost (from diagnosis to death) of hospitalization, visits, treatment, and part of the loss of production was approximately 106 000 Sw. cr. in the busulfan + radiotherapy group, 116 000 in the busulfan group, and 178 000 in the antimetabolite group. It is suggested that a prospective, randomized, controlled study could confirm that the present antimetabolite induction may lead to a more rapid remission induction in CML without more side-effects. However, to prevent early relapse, antimetabolite induction should be combined with busulfan maintenance treatment.

In a consecutive series of 22 patients with acute leukemia, the total body potassium was studied in 18 patients on 39 occasions during relapse and remission. Total body water was also determined. A control group consisting of 88 age-matched healthy volunteers was also studied. The patients had a significantly lower mean potassium concentration, per kg body weight, per kg lean body mass and per kg water, than the controls (p less than 0.001). Individually, 11 out of the 18 patients had at least one value below the lower 95% confidence limit. Hypokalemia was frequent both in the patients with low (7/11) and normal (3/6) potassium per kg lean body mass. Five of 13 investigated patients showed laboratory indications of secondary hyperaldosteronism, which might be partly responsible for the hypokalemia. Increased serum or urine levels of lysozyme were found in 62% of the patients.

Cytostatics are toxic, and individual variations in drug metabolism large. Therefore the possibility to predict which cytostatic combination should be abandoned because it will not lead to a remission was studied in 58 leukemia patients. A simple following of changes in white blood cell, platelet and blast cell numbers in peripheral blood (combined into so-called chemotherapy points) makes it possible to predict which patients in the presenting phase of AML will achieve remission, but this was possible neither in the relapse phase of AML, nor in promyelocytic or monocytic leukemias. All 27 patients in the initial phase of AML, who later were to achieve remission, had less than 12 chemotherapy points, and 9 of 11 patients who did not achieve remission had over 13 points. Therefore the cytostatic combination should be changed in patients who, after two courses of treatment, have over 13 points.

The frequency of fever days was measured in 67 patients with acute leukemia in the initial phase until remission was obtained or the patient died. A total of 3411 hospital days were studied. Three antibiotic schedules were examined between 1970 and 1975. There were 50% fever days when penicillin and streptomycin were combined as initial antibiotics, 37% when cephalosporin and gentamycin were used, and 31% when, in addition, semi-isolation was used prophylactically and granulocytes were given in a therapeutic attempt (0.05 greater than p greater than 0.01). The corresponding frequencies of early death were 9/21 (43%), 6/23 (26%) and 5/23 (22%). Early death occurred on an average 14, 23 and 21 days after admission. The frequencies of remission (complete and partial) were 8/21 (38%), 12/23 (52%), and 13/23 (57%). A randomized subgroup (12 patients) with intestinal sterilization was studied separately. It had 28% fever days, which is significantly less (p less than 0.01) than in the 13 patients given the same systemic antibiotics without intestinal sterilization. Fever was significantly lower (0.05 greater than p greater than 0.01) on the day after a series of granulocyte transfusions than before, although only 10(9) granulocytes were given. However, this fever reduction may have been due to concomitant antibiotics.

A 36-year-old woman with acute myeloblastic leukemia (M2) achieved complete remission in Feb. 1973, after ten weeks of chemotherapy with rubidomycin-cytosine arabinoside. She received weekly immunotherapy with bacillus Calmette-Guerin and allogeneic non-irradiated blast cells and monthly chemotherapy with thioguanine-cytosine arabinoside as maintenance. The bone marrow remained normocellular for 20 months. A first relapse occurred after this period. A second remission was achieved by seven courses of different cytostatic combinations. A second relapse, refractory to all cytostatic combinations tried, occurred in June 1976. She was thereafter in relapse until her death in July 1980. Autopsy showed extensive leukemic infiltration in bone marrow, liver, spleen, pericardium, stomach, and lymph nodes. Cytochemistry, surface markers, the capacity to stimulate lymphocytes, the in vitro growth pattern (colony-forming unit culture) of bone marrow and biochemical analyses did not give any remarkable results. In contrast, the peripheral blood cells produced a normal amount of colony-stimulating activity, which is significantly more than that produced by the blood from other leukemia patients. In liquid culture, the peripheral blood cells from this patient also seemed to live longer and mature more than cells from other leukemia patients. Finally, the peripheral leukemic cells from this patient seemed to produce far less leukemia-associated stem cell inhibitor than cells from other leukemia patients. The normal colony-stimulating activity production by leukemic cells and the absence of leukemia-associated stem cell inhibitor may therefore explain the long survival of this patient in relapse.

The iron metabolism has been studied in 11 patients with porphyria cutanea tarda. Despite significantly increased amounts of iron in the serum and liver, the porphyria patients absorb not less but significantly more radioiron than normal controls. Whereas phlebotomy-induced iron deficiency stimulates the absorption in controls, no further stimulation is found in the porphyria patients. The plasma iron turnover is high in the porphyria patients, and some of this iron is probably deposited in the liver. The relationship between the high iron absorption, high plasma iron turnover, high liver iron, liver damage and uroporphyrin production in the liver is discussed. It is suggested that two concurrent genetic defects may cause porphyria cutanea tarda, one in iron absorption and one in porphyrin synthesis by damaged liver cells. The absorption of inorganic iron was higher than that of hemaglobin iron. The possible damage which fortification with inorganic iron could cause to the very small group of porphyria patients is discussed.