Conduct of the study
After fulfilling the inclusion criteria, and after informed consent
has been documented, the patients will be randomly assigned (“randomised”)
to standard treatment (Mitoxantrone) or to investigative treatment (ASCT).
This term refers to the random selection by a computer, meaning the
treatment will be determined by chance to enable balancing of the two
groups of patients. The physician can explain the importance of this
procedure in more detail. Either therapy will be initiated within several
weeks after the entry in the study.
All randomized patients will be evaluated clinically at 6 months intervals
and by means of MRI (Magnetic Resonance Imaging) at one year intervals,
until progression occurs or until the end of the study.
HSCT
In case of randomization to the investigative treatment (ASCT), the following consecutive procedures will be executed:
- 1.”mobilisation” refers to interventions which lead
to the harvesting of hematopoietic stem cells: at first a one day
infusion of high dose of the immunosuppressive drug Cyclophosphamide
will be administered, followed by daily subcutaneous injections
of a specific growth factor (filgrastim) starting 5 days after the
last infusion of cyclophosphamide. As a result, stem cells will
migrate from the bone marrow to the blood, and sufficient numbers
can usually be counted in blood samples after 5-8 days of filgrastim
administration.
- 2.”leukopheresis” is the subsequent technical procedure used to isolate the mobilised stem cells from the blood. The leukopheresis machine connected to the body via either a peripheral vein or a catheter, collects the blood, removes the stem cells and returns the rest of the blood to the patient. The isolated stem cells are then stored frozen until needed for successive reinfusion (see next procedure).
- 3.”intense immunosuppression” or “conditioning” will be initiated 20-40 days after mobilisation, consisting of infusion of high dose combination of immunosuppressant drugs called BEAM (BCNU, Etoposide, cytosine Arabinoside and Melphalan) associated to Anti-Thymocite Globulin (“ATG”). Blood stem cells previously collected are then reinfused (autologous stem cell transplantation). ATG is a protein derived from rabbits with depletive effects on immune cells. Hospitalisation of several weeks (20-30 days) are usually required to carry out these steps, and to cover any unwanted side effects that may result as a consequence of the therapy. Antibiotic treatment and transfusion of red blood cells or platelet usually are necessary in the period immediately following the transplantation.
Mitoxantrone
Complications
The major risk of transplantation is an increased susceptibility to infections as a result of the severe marrow impairment following conditioning regimen.
Patients who undergo these procedures may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, fever, hair loss. All these symptoms are fully reversible and most patients can return to a normal life pattern. In men and women the ability to conceive is markedly reduced.
Severe, life threatening side effects are reported, albeit rare, and mostly within patients who undergo a transplant in a very advanced stage of their disease.
Mitoxantrone is generally well tolerated and has manageable side effects at the doses used here. The most common adverse effects are: nausea, menstrual disorders, diarreha, headache, back pain, urinary tract infections, stomatitis and temporary hair loss. As mitoxantrone may harm the foetus , adequate birth control methods should be used during treatment with this drug.
There is a well documented cardiac toxycity risk associated with a cumulative dose of mitoxanthrone, which means that treatment with this drug can occur only once in a lifetime.
There is also a documented risk of infertility with the both treatments.
