Autologous Bone Marrow Transplantation - Blog Science Connections

ABMTfor Breast Cancer 491
only adjuvant chemotherapy, but most of these had developed clinical
evidence of metastases while on or within 12 months of completing therapy.
Bone marrow was harvested only after bilateral iliac crest bone marrow
biopsies demonstrated at least a 40% cellularity and absence of metastatic
tumor. Marrow cells were obtained by multiple aspirations of the posterior
and occasionally the anterior iliac crests. Nucleated cells were concentrated
using a Haemonetics Model 30 Cell Separator and frozen in autologous
plasma and 10% dimethyl sulfoxide at a controlled rate of l°C/minute to
-80°C, then stored in the liquid phase of a liquid nitrogen freezer. The
concentration step resulted in a loss of approximately 25% of mononuclear
cells but retention of more than 90% of the granulocyte-macrophage colonyforming
cells. Final concentrated cell yields ranged from 1.31 -3.5 x 10 8 /kg
body weight; the mean was 2.37 x 10 8 /kg.
The first six patients were treated with cyclophosphamide alone in a
scheduled dose of 50 mg/kg/day for 4 days. One patient in this group,
however, developed gross hematuria after a total of 150 mg/kg and the fourth
dose was omitted. Patients 7 through 10 received 160 mg/kg of cyclophosphamide
over 4 days plus 300 mg/m 2 /day of carmustine on the first 3
days of the cyclophosphamide. The cryopreserved autologous bone marrow
cells were rapidly thawed in a 37°C water bath and infused approximately 36
hours after the final dose of cyclophosphamide.
Patients were treated in private rooms under mask and hand-washing
isolation. Laminar air flow was not used. Broad-spectrum antibiotics, usually
mezlocillin and gentamicin, were initiated when a patient's temperature
reached 38.5°C. Vancomycin was added for documented or suspected
gram-positive infection. Amphotericin B was initiated for documented
fungal infection or for unexplained fever persisting after 72-96 hours of
broad-spectrum antibiotics. Prophylactic platelet transfusions were given
when the platelet count fell to less than 30,000. All blood products were
irradiated, and cytomegalovirus-negative products were routinely used for
patients whose sera were cytomegalovirus-negative.
RESULTS
All patients became profoundly leukocytopenic, with circulating WBC
counts of less than 100/mm 3 , by day 2 after autografting, and all developed
fever requiring antibiotics. Platelet support was also required for all patients.
Median time for recovery to greater than or equal to 1000 WBCs/mm 3 was 14
days postautograft and for recovery of a self-sustaining platelet count of
50,000, 21 days. Hematopoietic recovery time did not correlate with the
number of marrow cells infused. There was no difference in time to
granulocyte recovery between the group treated with cyclophosphamide
alone and those treated with the combination of cyclophosphamide and
carmustine, but platelet recovery occurred later in the combined alkylating