Autologous Bone Marrow Transplantation - Blog Science Connections

CML Chronic Phase Autografting 193
There were few complications of the chemotherapy. All patients had
temporary chemotherapy-induced mucositis. Grand mal convulsions occurred
in two cases on day 3, and thereafter patients were treated with prophylactic
phenytoin from day 1 (8). In three patients amphotericin B-responsive fungal
infections developed, and in eight bacterial infections responsive to antibiotics
developed. There were no treatment-related deaths.
DISCUSSION
We do not yet know whether the induction of Ph 1
negativity will prolong the
duration of the chronic phase of CML, but we have found it to be a regular,
though usually a partial and transient, phenomenon. Deliberate attempts to
induce the regeneration of Ph 1 -negative hematopoietic cells in chronic phase
CML by intensive treatment intended to ablate the dominant Ph 1 -positive
population have not been successful in prolonging the duration of the chronic
phase (9). Our observation that cryopreserved buffy coat leukocytes
administered to rescue a patient whose human leukocyte antigen-matched
allograft failed to grow led to the appearance of Ph 1 -negative metaphases
during the early months after autografting suggested that autografting in the
chronic phase of CML offered a possible way of prolonging the duration of the
chronic phase and of investigating the circumstances in which Ph 1 -negative
cells had a growth advantage. In the work reported here our intention was to see
whether autografting affects the duration of the chronic phase and to determine
the frequency of appearance and the duration of persistence of Ph 1 -negative
metaphases in the postautograft period.
Engraftment was rapid in all patients except one who received a supplementary
autograft on day 80 because of continuous pancytopenia (persistent
WBC count of only 1 x 10 9 /1, platelets < 10 x 10 9 /1, and a continuing blood
transfusion requirement). No therapy-related deaths were seen. The convulsions
related to high-dose busulphan therapy appear to have been prevented in
subsequently treated patients by anticonvulsant therapy. Eleven patients
survive in good health, seven requiring no treatment, which may or may not be
of clinical advantage.
The occurrence of lymphoid blast transformation in two patients 6 and 8
months after autograft could mean the autograft expedited the growth of a
previously transformed cell population or that it induced the transformation.
Ph 1 -negative hematopoiesis has been seen after autografting with bloodderived
buffy coat cells or autologous bone marrow. The origin of the
Ph 1 -negative cells seen in the patients in this series is uncertain, but it is likely
that they arise from the autograft and indicate a temporary growth advantage
over the Ph 1 -positive cells in hypoplastic bone marrow. In this circumstance it is
possible that Ph 1 -negative stem cells react better to homeostatic influences
than Ph 1 -positive cells. In patient 4, however, the delayed and prolonged
Ph 1 -negative hematopoiesis could have been endogenous.