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Autologous Bone Marrow Transplantation - Blog Science Connections

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Autografting in Chronic Granulocytic Leukemia 201<br />

marrow cells collected 4 months after HDM treatment, but these also failed to<br />

engraft. However, she is still alive despite pancytopenia 9 months after the initial<br />

ABMT. No marrow metaphases were obtained after transplantation.<br />

Two patients who underwent autografts with marrow containing a mixture<br />

of Ph 1 -positive and Ph 1 -negative cells experienced prompt engraftment. One<br />

patient (patient 1, Table 1) had a minority of Ph 1 -negative metaphases (20/53)<br />

in transplanted marrow. She had a normal WBC count 4 months after ABMT.<br />

Cytogenetic studies revealed 50% and 40% Ph 1 -negative marrow metaphases 2<br />

and 3 months after transplantation. The karyotype showed 96% Ph 1 -positive<br />

marrow cells when a typical hyperleukocytosis was detected 4 months after<br />

transplantation. This patient is still in stable chronic phase 7 months after ABMT<br />

and 46 months after diagnosis. Ph 1 -negative marrow metaphases have<br />

disappeared.<br />

For the other patient (patient 2, Table 1), marrow with a majority of<br />

Ph 1 -negative cells (33/44) was transplanted. The WBC count is still normal 18<br />

months after ABMT. More than 500 marrow metaphases were examined<br />

during the first 6 months following transplantation, and very few Ph 1 -positive<br />

cells were found. But afterwards, the percentage of Ph 1 -positive marrow cells<br />

increased slowly, attaining 64% 1 year after transplantation.<br />

DISCUSSION<br />

High-dose melphalan was used to treat some patients with Ph 1 -positive<br />

CGL during the chronic phase to reduce the Ph 1 -positive contingent. No effect<br />

was observed in two patients in whom 100% Ph 1<br />

-positive marrow cells persisted<br />

and in whom ABMT subsequently failed to engraft. In one patient, the number of<br />

thawed CFU-GM cells (0.75 x 10 4<br />

CFU-GM cells/kg) infused, was low. This<br />

number was not abnormal for the other patient, who received 3.8 x 10 4<br />

CFCl-<br />

GM/kg. Such graft failures have been reported in CGL after ABMT but not after<br />

transplantation of blood-derived stem cells (7), and the failure might be<br />

explained by the particular fragility of CGL marrow progenitors in the freezing<br />

process (12).<br />

After HDM treatment, the two other patients achieved partial remission<br />

defined by the disappearance of a substantial proportion of Ph 1<br />

-positive marrow<br />

Table 1. Number and Proportion of Ph 1 -Negative to Ph 1 -Positive <strong>Marrow</strong><br />

Metaphases After <strong>Autologous</strong> <strong>Bone</strong> <strong>Marrow</strong> <strong>Transplantation</strong><br />

Months After ABMT 1-2 3 4 5-6 7-9 9-12<br />

Patient 1 5/10 12/30 1/24 — 0/31 —<br />

(50%) (40%) (4%)<br />

Patient 2 190/191 253/257 105/106 40/50 36/100<br />

(99.5%) (98.5%) (99%) (80%) (36%)<br />

Abbreviation: ABMT, autologous bone marrow transplantation.

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