Blood, 1961, Vol. 17, No. 1, pp. 1-19.
© 1961 American Society of Hematology, Inc.
Busulfan in the Treatment of Chronic Myelocytic Leukemia.
The Effect of Long Term Intermittent Therapy
A. HAUT 1,
W. S. ABBOTT 1,
M. M. WINTROBE 1, and
G. E. CARTWRIGHT 1
1 Department of Medicine, College of Medicine, University of Utah, Salt Lake
City, Utah.
1. The observations made during the administration of 114 courses of busulfan to 30 patients over a period of seven years are recorded. The responses to
initial courses of therapy corresponded with those reported previously. With
repeated courses of therapy, subjective improvement, the decline in the
number of leukocytes, decrease of anemia and the subsidence of physical
signs of the disease were as satisfactory as during the first course but tended
to appear later. Patients were ambulatory and most were symptomatically and
objectively improved during and after repeated courses as compared to their
status beforehand.
2. Remissions were longest when the leukocyte values were 10,000 per cu.
mm., or less, at the time busulfan was discontinued. Among such patients,
remissions of six months or longer were seen in 85 per cent after the initial
course of busulfan but in only 19 per cent after fifth or later courses.
3. Evidence of partial resistance to busulfan was seen in some cases after
multiple courses of treatment. Complete resistance occurred in 15 patients upon
development of the acute, myeloblastic phase of chronic myelocytic leukemia.
When busulfan failed, 6-mercaptopurine and colcemide were temporarily of
value; x-ray was not of benefit. After the onset of the acute phase. the median
survival was three months. This mode of termination is probably no more
frequent (50 per cent of cases) since the advent of busulfan therapy than
before.
4. If anemia was not relieved, or a large spleen was not reduced 50 per cent
in size following a course of therapy, the prognosis was poor and the acute
phase imminent.
5. Thrombocytopenia in early, untreated cases was not necessarily a bad
sign, nor was the use of busulfan precluded because of it. However, when
thrombocytopenia appeared in a previously treated patient, without other
evidence indicating busulfan toxicity, or when it occurred in a patient with
three or more years of known disease, it usually presaged the development of
the terminal acute phase.
6. Side effects of busulfan were significant in only one patient; this man
received 8 milligrams daily, double the usual dose, for eight months and
developed glossitis, anhydrosis and alopecia totalis. The major hazard in the
use of the drug was the occurrence of pancytopenia. This could be related to
excessive dosage.
7. Morbidity was clearly decreased. Longevity (median 42 months) was
greater than in Minot’s untreated cases (median 31 months) and at least as
great as that achieved by treatment with radioactive phosphorus and x-ray
(median 32-41 months). Repeated courses of busulfan are considered to offer
an effective and practical palliative form of therapy for chronic myclocytic
leukemia, up to the time of appearance of the terminal acute myeloblastic
phase.
Submitted on August 29, 1960
Accepted on October 15, 1960
