Autologous Bone Marrow Transplantation - Blog Science Connections

196 CML Blast Crisis Autografting
eight as myeloid (two basophilic, two monocytic, one myelomonocytic, one
megakaryocytic, two undifferentiated). Two of the ten patients had received
bone marrow transplants for chronic phase (CP) CML 2 and 4 years previously
and had relapsed with myeloid blast crisis. Two other patients had Philadelphia
chromosome-negative CML. The median age of the group was 51 years
(range, 32-59 years). Two patients had hypertensive heart disease and another
had had a splenectomy 2 years before undergoing autografting. The median
duration of the chronic phase before the onset of blast crisis was 3.3 years
(range, 0.3-6.5years). The median white cell count at transformation was 100 x
109/1 (range, 40-250 x 10 9 /l) with over 50% of blasts in the blood. Mitoxantrone
(12 mg/m 2 ) was given by half-hour infusion daily on days 1-5 and cytarabine (1
g/m 2 ) was given twice daily by 2-hour infusion on days 1 -3. Melphalan (120
mg/m 2 ) was given by bolus injection on day 7, and an autograft of cryopreserved
peripheral blood buffy coat cells (10x10 8 /kg) was infused on day 9
in six patients and on day 11 in four. Once the chronic phase was restored,
maintenance chemotherapy with vincristine (weekly), prednisolone (for 5 days
every 4 weeks), oral methotrexate, and mercaptopurine (daily) was given to the
patients with LBT.
The technique for collection, cryopreservation, reconstitution, and infusion
of buffy coat cells has been described (5). Two patients whose infusions failed to
engraft by day 23 received another dose of 10 x 10 8 /kg of buffy coat cells on day
25. The second chronic phase was defined as clearance of all blast cells from
the peripheral blood and less than 5% blast cells in the bone marrow.
RESULTS
All patients were restored to a second CP. Engraftment occurred at a
median of 18 days (range, 12-40 days). This includes the two patients who had
a supplementary autograft at day 25. The median duration of the second CP
was 6+ months (range, 5-14+ months). Localized bone pain, which responded
to radiotherapy (30 Gy in ten fractions), occurred in three patients whose blood
and bone marrow remained in CP. Blasts recurred in the blood and bone
marrow in three other patients 5, 6, and 8 months after autograft. A second
attempt at cytoreduction and autograft with the same chemotherapeutic
regimen was carried out in two of the three. Both patients died with
pancytopenia and disseminated fungal infections. The third patient received
mitoxantrone and cytarabine alone because the supply of cryopreserved cells
was exhausted. His leukemia returned to a CP that lasted for 2 months. Two
other patients died in accelerated phase, one of a cerebrovascular accident 6
months after autograft and the other of septicemia and renal failure 13 months
after autograft. Five patients are alive with second CP of blood and bone marrow
(range, 5-14 months).
All patients had nausea, vomiting, and mucositis. Seven patients had
fungal infections (2 had disseminated candidiasis, 3 had gastrointestinal