Autologous Bone Marrow Transplantation - Blog Science Connections

ABMT Timing in Lymphoma 281
PATIENTS AND METHODS
Patients with large B-cell lymphoma received transplants from March
1981 to December 1985, and no data collected after June 1,1986, is included
in the analysis. The patients were evaluated at Memorial Hospital and were
treated using protocols approved by the institutional review board (IRB).
Staging work-up included confirmation of pathological diagnosis, and the
highest pretreatment serum LDH level recorded is listed in Tables 1 and 2.
Tumor dimensions were measured at surgery, x-ray evaluation, or both and
are also given in Tables 1 and 2. Bone marrow aspirate and biopsy specimens
were evaluated for cellularity, morphological presence of lymphoma, growth
of colony-forming units granulocyte-macrophage (CFCIs-GM) or erythrocyte
burst-forming units (BFCls-E), and immunoglobulin surface markers. Bone
marrow was considered involved if greater than 5% lymphoma cells were
detected. Because it is difficult to distinguish between small numbers of
lymphoma cells and normal lymphoid precursors without using special
procedures, any patient with less than 5% blasts that appeared lymphoid by
cell-surface marker analysis, morphology, or both was considered to have
probable bone marrow involvement. The patient's disease status and bone
marrow were reevaluated after completion of induction therapy.
All previously untreated patients with poor prognostic features were
induced using the L-17M protocol (28), requiring cyclophosphamide on day
1 and day 35. Vincristine was given intravenously on days 1,8,15,22, and 29.
Prednisone was given by mouth from day 1 through day 35, and then administration
was tapered with Bactrim (trimethoprim and sulfamethoxazole) prophylaxis.
Doxorubicin was given intravenously on days 16, 17, 18, and 35.
Intrathecal methotrexate was given four times during the induction phase.
Bone marrow was harvested after hematologic recovery from the last part of
induction therapy. Bone marrow harvest was performed with the patient
under general anesthesia, and heparinized bone marrow was enriched for
mononuclear cells by unit gravity sedimentation in the presence of 0.8%
hydroxyethyl starch (HES). Bone marrow with no suggestion of involvement
by lymphoma was cryopreserved in 6% HES, 5% dimethyl sulfoxide (DMSO),
4% human albumin at 4-5 x 10 7 cells/ml (29). Patients with probable bone
marrow involvement at presentation had their marrow divided into two
aliquots. Sixty percent of their marrow was purged with 4-hydroperoxycyclophosphamide
(4-HC) (60-120 JUM) (30-34) for 30 minutes at 37°C and
cryopreserved and used first for hematopoietic reconstitution. The other 40%
was cryopreserved to be used as backup for the purged bone marrow.
Patients then received one cycle of daunomycin, ara-C (cytarabine), and
6-thioguanine (DAT) chemotherapy (28), which allowed adequate time to
evaluate the cryopreserved bone marrow's viability, cell-surface markers, and
CFO-GM and BFCI-E growth. The initial protocol called for randomization of
patients to arm 1 (receive transplant following induction) or to arm 2
(continue on consolidation and maintenance phase of L-17M and consider