Stem Cell and Bone Marrow Transplants for Cancer

Leukemia therapy uses different methods, used in association or sequentially, with the aim of obtaining a better quality of life and remission of clinical signs. There chemotherapy involves the oral or intravenous administration of one or more cytostatic drugs, which stop the proliferation of tumor cells.

Chronic myeloid leukemia was the first tumor form for which a specific drug (Imatinib mesylate) was introduced, active against leukemic cells with the Philadelphia chromosome. This effective tyrosine kinase inhibitor it was the progenitor of a new treatment strategy, even if over the years it has been understood how tumor clones can develop a form of resistance to its pharmacological action following a genetic mutation. Currently, research is testing alternative tyrosine kinase inhibitors, capable of intervening in cases where Imatinib mesylate loses its effectiveness. The biological therapies (example: interferon) exploit the body’s natural immune component to recognize and destroy altered or unwanted cells. Finally, the radiotherapy It allows the use of high-energy rays to damage leukemia cells and stop their growth.

First part
Leukemia Treatment: Drugs, Chemotherapy and Other Treatment Options

Stem Cell and Bone Marrow Transplant: What Are They?

In recurrent cases or when standard treatments do not promise a good prognosis, more aggressive therapeutic alternatives can be considered, such as autologous transplant or allogeneic stem cells.

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 recipient’s hematopoietic and immune system.

Before a stem cell transplant, the patient undergoes high doses of chemotherapy or radiotherapy to reduce the tumor residue and to destroy the diseased bone marrow (myeloablative therapy). Subsequently, the hematopoietic organ, in conditions of marrow aplasia, must be reconstructed, by:

• Stem cell transplant: the cells are taken from the peripheral blood (through mobilization with high-dose cytostatic therapy) of the patient himself or collected from a compatible donor and, subsequently, reinfused into the leukemic subject through a blood transfusion. The stem cell suspension will help rebuild the bone marrow.
• Bone marrow transplant: the cells are taken directly from the hematopoietic organ by fine needle aspiration.

Autologous vs Allogeneic Transplant: What are the Differences?

Two different forms of transplant can be distinguished:

• Autologous transplant: before high-dose chemotherapy, stem cells or a bone marrow sample are taken from the patient and cryopreserved.
• Allogeneic transplant: the subject receives stem cells or bone marrow from a suitable partially or totally histocompatible donor (example: HLA-identical sibling, haploidentical family member or non-family HLA-identical donor).

In the case of allogeneic transplantation, the transplanted stem cells, T and NK lymphocytes of the donor can react against any residual leukemic clones (immune-mediated anti-tumor effect, called “Graft Versus Leukemia“), as well as 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.

The conditioning (preparatory phase for transplantation) has the dual purpose of:

• reduce residual pathological cells as much as possible (eradicate the pathology)
• in allogeneic bone marrow transplant, “prepare” the engraftment of the donor’s stem cells within the recipient’s marrow cavity and induce profound immunosuppression to avoid rejection.

24-48 hours after the end of conditioning, we move on to the actual transplant phase. The 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 on their own. During the subsequent phase “of hematopoietic engraftment“stem cells are able to settle in the bone marrow microenvironment and initiate the resumption of hematopoiesis, with the leukocyte, platelet and hemoglobin counts rising after 15-30 days.

How does stem cell mobilization happen?

Hematopoietic progenitors circulating in the peripheral blood can be collected by leukapheresis (procedure that allows the collection of hematopoietic stem cells from peripheral blood), then cryopreserved and subsequently transplanted to reconstitute the hematopoietic system of neoplastic patients subjected to the previous conditioning phase (before the transplant, patients are treated with potentially curative (but myeloablative) doses ) chemotherapy or radiotherapy).

Advantages of the procedure compared to bone marrow transplant:

• avoid general anesthesia;
• collects stem cells even in the case of previous radiotherapy on the pelvis;
• faster engraftment after infusion;
• reduction of infectious and hemorrhagic toxicity related to cytopenia after conditioning.

The objective of hematopoietic stem cell transplantation is therefore identified with recovery. Achieving this condition depends in turn on the achievement of the following main objectives:

1. The total disappearance of the totipotent stem cell compartment: is achieved by subjecting the patient to an eradicating cytostatic therapy (chemotherapy or radiotherapy) in the phase preceding the transplant (conditioning phase).
2. For thehematopoietic engraftment of reinfused stem cells, it is essential to overcome the reaction to the transplant, mediated by the immunocompetent cells:
   

   – of the patientresponsible for rejection (a serious complication in which the body rejects the transplanted cells);
   – of the donorresponsible for graft-versus-host disease (Graft versus Host diseaseGVHD), in which the reinfused cells reject the organism into which they were transplanted.

Stem or bone marrow transplant 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 conditions allow, stem cell transplant can also be carried out in older subjects, adapting the procedure to the specific clinical case of leukemia (for example using lower doses of chemotherapy to obtain myeloablation).

Other articles on ‘Leukemia – Stem Cell Transplant and Bone Marrow Transplant’

1. Leukemia: Cure and Treatment
2. Leukemia
3. Leukemia – Causes, Symptoms, Epidemiology
4. Leukemia: Diagnosis
5. Therapies for the various types of leukemia
6. Side Effects of Leukemia Treatments