VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

16 (800 mg/m2 per day for two consecutive days, intravenously), cyclophosphamide
(60mg/kg per day for each of two consecutive days) followed by 10 Gy of
Total body irradiation at a dose rate of 5-9 cGy/min. Within 24 hours following
radiation, the cryopreserved Ph-negative BSC were defrosted and reinfused intravenously.
This is designated Day O.
RESULTS
Twenty patients in CP-CML or AP-CML have so far been treated with this
intensive inductive regimen. Eleven (55%) out of 20 patients (CP:9/16 patients;
AP:2/4 patients) had suppression on BSC of Ph-positive metaphases to 100%
and 3 other CP-CML patients had a major Ph-suppression to less than 50% of
Ph-positive metaphases. An interesting result derived from the PCR analysis
performed on the BSC of 7 patients (AP:2 patients; CP:5 patients). The results of
this analysis failed to show in the patients with CP-CML the presence of an amplification
fragment of 273 bp, corresponding to the presence of BCR-ABL hybrid
transcripts with a junction between the "BCR" region exon 3 and the ABL
exon 2, which was expected on the basis of a PCR performed on the patient cells
before treatment.
Five patients (AP:1; CP:4) have been so far transplanted with Ph-negative
BSC. Hematological recovery after transplant to >l.Oxl09/L neutrophils and
>25xl0 9
/L platelets occurred in all patients, at a median of 29 and 40 days post-
ABMT, respectively. All the patients in CP-CML received rh-G-CSF at the dosage
of 5ug/Kg/die. Graft failure occurred in 2 patients (CP:1 patient; AP:1 patient)
and both died of fungal and Gram negative septicemias, despite that we
had infused both patients with autologous marrow cells, previously harvested
and cryopreserved. During the initial phase of hematopoietic regeneration post-
ABMT in the other 3 patients, only Ph-negative marrow cells were detected.
Currently, 3/4 patients with CP-CML maintain a clinical and cytogenetic
remission at 3, 7 and 14 months; of these, one is in biological and citogenetic remission
(Ph-/PCR).
DISCUSSION
The preliminary results of this trial seem encouraging for a number of reasons.
First of all, they provide strong support for the view that Ph-negative hematopoietic
stem cells can be harvested after an intensive conventional chemotherapy;
besides, these cells can result in a consistent and sustained restoration
of Ph-negative (and PCR-negative) hematopoiesis. The best condition to achieve
these results is avoiding the treatment with a-IFN in non-responding patients or
at least, leaving a period of time of at least 2 months between the last day of a-
IFN administration and the beginning of mobilizing therapy. In our series, we
have observed an important delay of hematopoietic recovery after intensive conventional
chemotherapy in patients pre-treated with a-IFN versus patients pretreated
with chemotherapy.
At the end, caution, however, must be used about the conclusive significance
of these results. In fact, BSCs may have a very low mitogenic activity and
this, of course, could bias the results of the cytogenetic analysis. Moreover, the
negative results of the PCR analysis could also be due to the lack or to a very
low degree of expression of the bcr/abl transcripts at the BSC differentiation
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 213