Autologous Bone Marrow Transplantation - Blog Science Connections

792 CML Chronic Phase Autografting
RESULTS
There was early evidence of trilineage engraftment in all 13 patients.
However, one patient (number 12) required an additional autograft without
preconditioning at day 84. Two other patients required blood transfusions up to
4 months after the autograft. The mean duration of neutropenia (neutrophils
< 500 x 10 8 /1) in the 12 patients (excluding number 12) was 30 days (range,
20-48 days) and of thrombocytopenia (platelets < 50 x 10 9 /1) was 39 days
(range, 33-60 days). In one of two patients who had prolonged thrombocytopenia
platelet antibodies were discovered; the platelet count increased after
treatment with corticosteroids. Apparent clinical normality (improved wellbeing,
impalpable spleen) with normal values for peripheral blood count and
normal results on bone marrow aspirate studies (normal fat spaces, normal
cellularity of trails, absence of myelocyte peak) was restored in the peripheral
blood and bone marrow for a median of 8 months (range, 2-30 months).
Cytogenetic analysis showed less than 30% Ph 1 -negative metaphases in
the marrow after hematopoietic recovery in ten of the thirteen patients treated.
The percentage of Ph 1 -negative cells remained at zero or diminished and
disappeared over 5-8 months in nine of the patients. Patients 5 and 8, whose
cytogenetic studies showed conversion from Ph 1 negativity to persistent Ph 1
positivity associated with a transition of their disease from morphological
normality to early chronic phase disease, were autografted on a second
occasion (one 8 months and the other 13 months) after the first autograft. One
of the two had a recurrence of Ph 1 -negative metaphases in the marrow 4
months after the second autograft. This Ph 1
negativity seen in five of five
metaphases analyzed was associated with a rising WBC count (96 x 10 9 /l). He is
currently being treated with or-interferon. The other patient who received a
second autograft remains Ph 1 positive.
In the case of the patient (number 4) who had received no previous
treatment, Ph 1 -negative metaphases appeared 4-6 weeks after the autograft
but were not observed in 20 metaphases, all of which were Ph 1 -positive,
analyzed 5 months after the autograft. However, they reappeared at 7 months
and were still present 12-17 months after the autograft. Cells from CFCI-GM
cultures from this patient at 11 and 12 months after the autograft showed only
Ph 1 -negative metaphases. Rearrangement of the bcr gene, which was present
at diagnosis, was not present in the Ph 1 -negative metaphases obtained after 8
months. Cytogenetic analysis 17 months after the autograft showed the
presence of a minority population (2/30) of Ph 1 -positive cells.
Lymphoid blast transformation occurred in two patients 6 and 8 months
after the autograft. Both subsequently died of resistant leukemia after autograft
despite intensive chemotherapy appropriate to adult lymphoblastic leukemia.
Eleven patients are alive, seven requiring no chemotherapy, up to 28 months
after their autograft. Their median survival after the autografting is 15 months
(range, 3-28 months).