Autologous Bone Marrow Transplantation - Blog Science Connections

4 AML in First Remission
used in patients older than 50 years and thus is less subject to strict age limits
than allogeneic BMT. On the other hand, since ABMT is not associated with
graft-versus-host disease and interstitial pneumonia, these advantages should
be weighed against the higher probability of relapse of leukemia after
transplantation.
Pilot studies carried out at several centers in first (5,6) and subsequent (7)
remissions of AML suggest promising results from marrow ablative cytotoxic
therapy followed by ABMT in patients with AML. These results now await
confirmation in prospective trials, since one could argue that patients who were
particularly good risks were selected for transplantation in those studies. To
assess the value of ABMT in patients with AML, we initiated a study in which
patients with newly diagnosed AML would receive ABMT or allogeneic BMT
following attainment of complete remission. Patients received allogeneic BMT
when they had an HLA-matched sibling donor and were between 15 and 45
years old; in all other instances, patients received ABMT.
STUDY DESIGNS AND METHODS
Patients received one or two courses of remission-inducing chemotherapy
(daunomycin and /3-cytosine arabinoside) and, after attaining complete
remission, a course of consolidation chemotherapy. Subsequently, the patients
received ABMT or allogeneic BMT unless early relapse interfered. During
complete remission, autologous bone marrow was harvested, cryopreserved,
and reinfused after conditioning chemotherapy and radiotherapy. Pretransplant
conditioning included two separate regimens, the first consisting of /3-cytosine
arabinoside (1 g/m 2
x 4) and amsacrine (115 mg/m 2 ) and the second of
cyclophosphamide (120 mg/kg) and total body irradiation of 8 Gy (lung dose, 7
Gy). The study was begun in December 1984, and our most recent analysis was
completed in June 1986. Bone marrow was collected from the iliac crest and
pelvic spine in 2- to 4-ml aspirates and collected in bottles containing
heparinized Hanks' balanced salt solution. The buffy coat (prepared by
centrifugation at 2,000 G) or Ficoll lsopaque-separated cells were filtered
through a nylon gauze and then through a glass filter. Nucleated cells were
counted in Turk solution. Samples from the graft were sent for bacteriological
and granulocyte-macrophage colony-forming unit (CFC1-GM) cultures. Cells
were frozen in 10% dimethyl sulfoxide and 20% fetal calf serum using a
controlled-rate freezer and stored at -196°C in liquid nitrogen (8). On 2
subsequent days, cyclophosphamide (60 mg/kg) was administered to the
patients in saline during a 1 -hour infusion under conditions of forced diuresis
(125 ml/hour). Following the start of the cyclophosphamide infusion, mesna
was given in divided portions at -10 minutes, +4 hours, +8 hours, and +12 hours
up to a total dose of 48 mg/kg on each of 2 days.
The marrow graft was thawed on day 0 (8) and then reinfused for 30-45
minutes. The marrow graft was tested with CFC1-GM cultures, which were