General information
The possibilities of treatment of leukemia depend on the type of disease, its stage, the patient's general health and his age at the time of diagnosis.
Chronic myeloid leukemia was the first tumor form for which a specific drug (Imatinib mesylate) was introduced, active against leukemia cells with Philadelphia chromosome. This effective tyrosine kinase inhibitor has been the forerunner of a new treatment strategy, although over the years it has been understood that tumor clones can develop a form of resistance to its pharmacological action following a genetic mutation. Currently, the research is experimenting with alternative tyrosine kinase inhibitors, capable of intervening in cases where Imatinib mesylate loses its effectiveness. Biological therapies (example: interferon) exploit the body's natural immune component to recognize and destroy altered or unwanted cells. Finally, radiotherapy allows the use of high energy rays in order to damage the leukemic cells and stop their growth.
Stem cell and bone marrow transplantation
In relapsing cases or when standard treatments do not promise a good prognosis, one can think of more aggressive therapeutic alternatives, such as autologous or allogeneic stem cell transplantation .
Premise : the sources of stem cells are represented by bone marrow, peripheral blood and umbilical cord. One can distinguish between transplant:
- Autologous : the patient gives himself the stem cells.
- patient's bone marrow;
- peripheral blood (mobilization).
- Allogeneic : stem cells are from a donor.
- donor bone marrow;
- peripheral blood (mobilization):
- umbilical cord (cord blood).
A stem cell transplant is a procedure that aims to replace the altered bone marrow with a wealth of healthy cells, obtained from a donor or from the patient himself, capable of reconstituting the hematopoietic and immune system of the recipient.
Before a stem cell transplant, the patient is given high doses of chemotherapy or radiotherapy to reduce the neoplastic residue and to destroy the sick bone marrow (myeloablative therapy). Subsequently, the hematopoietic organ, in a condition of marrow aplasia, must be reconstructed, by:
- Stem cell transplantation : the cells are taken from the peripheral blood (by mobilization with cytostatic therapy at high doses) of the patient himself or collected by a compatible donor and, subsequently, reinfused into the leukemic subject by means of a blood transfusion. Stem cell suspension will help rebuild bone marrow.
- Bone marrow transplant : the cells are taken directly from the hematopoietic organ by aspiration.
Two different forms of transplantation can be distinguished:
- Autologous transplant : stem cells or bone marrow samples are taken from the patient before high-dose chemotherapy and are cryopreserved.
- Allogeneic transplant : the subject receives the stem cells or the bone marrow from a suitable partially or totally histocompatible donor (example: HLA-identical sibling, haploidentical familial or HLA-identical non-familiar donor).
In the case of allogeneic transplantation, the transplanted stem cells, the T and NK lymphocytes of the donor can react against any residual leukemic clones (immunomediated anti-tumor effect, called " Graft Versus Leukemia "), in addition to allowing immunological reconstitution. Also for this reason, the allogeneic transplant, unlike the autologous one, seems to be potentially curative, especially if the treatment takes place before the patients have registered chemo-resistance.
Bone marrow transplant
Rationale for bone marrow transplantation : in the initial preparatory phase, called "conditioning regimen", a supra-maximal cytostatic anti-tumor therapy is administered. This intervention aims to reduce the neoplastic residue and to induce prolonged or irreversible aplasia (bone marrow failure). In the next stage, the injection of stem cells (transfusion) will allow the recovery of bone marrow function.
Conditioning (preparatory phase for transplantation) has the dual purpose of:
- minimize residual pathological cells (eradicate the pathology)
- in allogeneic bone marrow transplantation, "prepare" the engraftment of donor stem cells within the medullary cavity of the recipient and induce profound immunosuppression to avoid rejection.
At 24-48 hours from the end of the conditioning, we move on to the actual transplant phase. Healthy cells, previously collected and cryopreserved, are infused (or "reinfused" if it is an autologous transplant) intravenously. Thanks to recognition mechanisms mediated by specific molecules, the infused cells are able to find their way to the bone marrow alone. During the subsequent phase of " haematopoietic rooting " the stem cells are able to settle in the bone marrow microenvironment and to start the recovery of hematopoiesis, with the rise of the leukocyte, platelet and hemoglobin count after 15-30 days.
Mobilization of hematopoietic stem cells
Hematopoietic progenitors circulating in peripheral blood can be collected by leukapheresis (a procedure that allows the collection of hematopoietic stem cells from peripheral blood), then cryopreserved and then transplanted to reconstitute the haemopoietic system of neoplastic patients subjected to the previous conditioning phase (before transplantation), patients are treated with potentially curative (but myeloablative) doses of chemotherapy or radiotherapy).
Benefits of the procedure compared to bone marrow transplantation:
- avoid general anesthesia;
- collects stem cells even in case of previous radiotherapy on the pelvis;
- faster rooting after infusion;
- reduction of infectious and hemorrhagic toxicity linked to cytopenia after conditioning.
The goal of hematopoietic stem cell transplantation is therefore identified with healing. The achievement of this condition in turn depends on the realization of the following main objectives:
- The total disappearance of the totipotent stem cell compartment: is obtained by subjecting the patient to an eradicating cytostatic therapy (chemotherapy or radiotherapy) in the phase prior to transplantation ( conditioning phase ).
- For haematopoietic engraftment of reinfused stem cells, it is essential to overcome the transplant reaction mediated by immunocompetent cells : - of the patient, responsible for the rejection (a serious complication in which the organism rejects the transplanted cells);
- of the donor, responsible for the graft versus host disease (GVHD), in which the reinfused cells reject the organism in which they were transplanted.
Stem or bone marrow transplantation is a therapeutic option considered especially for young patients, as it requires good general conditions and involves an intense procedure and a prolonged hospital stay. Today, however, if the conditions allow it, stem transplantation can also be performed in older subjects, adapting the procedure to the specific clinical case of leukemia (for example using lower doses of chemotherapy to obtain myeloablation).
