Autologous Bone Marrow Transplantation - Blog Science Connections

200 Autografting in Chronic Granulocytic Leukemia
autologous bone marrow transplantation (ABMT) during the chronic phase of
the disease. The rationale for this strategy was based on several considerations.
First, among patients with CGL in transformation, those who received
autografts during the accelerated phase survived longer than those who did so
during overt blast crisis (5,6). Second, Ph 1 -negative hematopoiesis could be
restored in some patients (6,7), confirming the results obtained by Coulombel
et al. (8) who demonstrated the presence of Ph 1 -negative precursors in longterm
culture systems; Ph 1 -negative restoration could prolong the duration of
the chronic phase (4). Third, high-dose chemoradiotherapy during the chronic
phase could reduce the size of the stem cell compartment and thereby reduce
the chance of transformation (4).
Although in vitro purging methods failed to eradicate Ph 1 -positive cells in
CGL bone marrow harvests or buffy coats, a transient disappearance of Ph 1 -
positive metaphases (partial or complete) was commonly reported in patients
given high-dose chemotherapy during the chronic phase (9). This suggested
that a marrow harvest could be performed during this Ph 1 -negative period and
cryopreserved marrow could be used for autologous transplantation.
We have up to now performed transplantations in four patients during the
chronic phase of CGL with marrow purged in vivo by high-dose melphalan for
which antileukemic efficacy has been demonstrated in CGL (10,11).
PATIENTS AND METHODS
Four patients (median age, 25 years; range, 12-38 years) with Ph 1
-positive
CGL received high-dose melphalan (HDM, 140 mg/m 2 ) after a 9- to 84-month
period in stable chronic phase. This was followed by prolonged cytopenia with
fewer than 0.5 x 10 9
granulocytes/1 lasting 16-50 days (median, 31.5 days).
Marrow collection was performed 28-62 days (median, 57 days) after HDM, as
soon as the WBC and platelet counts reached 2 x 10 9 /1 and 100 x 10 9 /1,
respectively. Harvested marrow cells were cryopreserved using dimethyl
sulfoxide, then stored in liquid nitrogen. A few weeks later, patients underwent
ABMT after a standard conditioning regimen with cyclophosphamide (120
mg/kg) and total body irradiation (10-12 Gy). A median of 1.55 x 10 8
(range,
0.8-3.8 cells) nucleated cells/kg was transfused containing a median of 2.1 x
10 4 (range, 0.75-3.8 cells) colony-forming units of granulocyte-macrophage
(CFG-GM)/kg.
RESULTS
In two patients the cells failed to engraft. Both had received transplanted
marrow containing 100% Ph 1
-positive cells. Of these two patients, one returned
to a stable chronic phase after a second transplantation of peripheral blood
stem cells collected during the original evaluation. He is still alive 8 months after
initial ABMT. The other patient had a second autologous transplantation of