The definition of
leukopenia was as follows: 1) WBC became less than 3,000/mm3 during
chemotherapy for patients with pre-treatment WBC more than 4,000/mm3, or 2) WBC decreased more than 1,000/mm3 in patients with pre-treatment WBC between 3,000 and 4,000/mm3. The incidence rates of
leukopenia by age, gender, and regimens of
chemotherapy were calculated. The case-control study was done between the control and the
leukopenia groups excluding patients suffered from
agranulocytosis to clarify the hematological and biochemical characteristics of the
leukopenia group. The control patients were chosen in the following way. For each patient with
leukopenia, a patient with the same admission year, same gender, same regimen of
chemotherapy, and the nearest age was chosen as a control patient. The changes in counts of white blood cell, granulocyte, and platelet, in
hemoglobin concentration, and in hepatic
enzyme levels before and during
chemotherapy were compared between the
leukopenia and the control groups.
Thrombocytopenia was defined as platelet count less than 15 x 10(4)/mm3 and hepatic dysfunction as either asparate
aminotransferase (AST) higher than 31 IU/l or
alanine aminotransferase (ALT) higher than 34 IU/l.
RESULTS: (1) Incidence rate of
leukopenia The
leukopenia appeared in 36 patients (14 men, 22 women), two (one man, one woman) of whom showed
agranulocytosis. The incidence rate was 1.2% (14/1,153) for men and 5.9% (22/372) for women. The incidence rate of women was higher than that of men in the age groups between 20 to 79 y.o., but no difference was seen in the age groups elder than 80 y.o. There were no differences in the incidence rate among groups treated with HRE (E:
ethambutol), HRS (S:
streptomycin), and HREZ (Z:
pyrazinamide). The
chemotherapy was continued in 30 patients after the appearance of
leukopenia, and the natural recovery from
leukopenia was seen in 19 patients, while the leukopenic state lasted during the
chemotherapy in the remaining 11 patients. In two patients who exhibited
agranulocytosis all drugs were discontinued. In the remaining 4 patients one or more drugs were discontinued. (2) Case-control study between
leukopenia (N = 34) and the control (N = 34) groups There were no differences in age, sputum culture positivity on admission, degree of roentgenographic extent of the disease, ratio of cavity formation, and quantity of daily doses between the two groups. There was also no difference between the days until
leukopenia appeared after starting
chemotherapy (47.6 +/- 29.5 days) in the
leukopenia group, and the days until WBC count became minimum within 3 months after starting
chemotherapy (41.7 +/- 21.0 days) in the control group. The negativity of
tuberculin skin testing was higher in the
leukopenia group [7/14 (50%)] than in the control group [1/10 (10%)], however, the difference was statistically not significant due to rather small size of cases. Before the starting
chemotherapy, the counts of WBC (7,230 +/- 1,530 vs 5,500 +/- 1,510/mm3, p < 0.001), neutrophil (5,230 +/- 1,450 vs 4,320 +/- 1,620/mm3, p < 0.05), lymphocyte (1,440 +/- 830 vs 830 +/- 440/mm3, p < 0.001) and platelet (34.9 +/- 12.2 vs 24.1 +/- 6.4 x 10(4)/mm3, p < 0.001) in the peripheral blood and the
globulin level (3.71 +/- 0.61 vs 3.35 +/- 0.61 g/dl, p < 0.05) in the serum were significantly higher in the control group than in the
leukopenia group. The decrements in the counts of WBC and granulocyte during
chemotherapy were larger in the
leukopenia group than in the control group (delta WBC: 2,880 +/- 1,530 vs 1,910 +/- 1,520/mm3, and delta Neut: 2,840 +/- 1,510 vs 1,820 +/- 1,380/mm3, p = 0.01, respectively), but the counts of lymphocyte were similar in both groups. The platelet counts also decreased in both groups, but to the mid-normal level in the control group, and to the lowest normal level in the
leukopenia group, in which 15 out of 34 patients (44%) showed
thrombocytopenia. The levels in the serum of hepatic
enzymes such as AST, ALT, and gamma-
GTP (gamma-glutamyl
aminotransferase) increased during
chemotherapy in the
leukopenia group, while decreased in the control group, and the facts indicate that in the former not only bone marrow cells but also hepatic cells were impaired by
anti-tuberculosis drugs.
CONSIDERATIONS: