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Allogeneic stem cell transplantation with myeloablative conditioning

Background

Donor

A blood related donor is preferred and currently, a blood related donor with up to one incompatible HLA (human leukocyte antigen) can be used. 

If the patient does not have a blood related donor, it is considered whether an unrelated donor with HLA, A, B, C, DR and DQ identity can be used. Despite serological techniques, unrelated donors may still have small differences in their HLA molecules which are of significance for GVHD and rejection reactions, therefore genomic typing is performed.

In younger patients, a stem cell transplantation for acute and chronic myeloid leukemia with marrow from an unrelated HLA genetically identical donor has given almost the same results as using stem cells from blood related donors.

The upper age limit for patients accepting stem cells from unrelated donors is somewhat lower than for patients who have a blood related donor because the risk for complications is greater and increases with age.

If it is not possible to find a living donor for the patient, searching for cord blood as a source of stem cells may be an altenative.

Stem cell harvesting

Hematopoietic stem cells are harvested by extracting bone marrow from the donor's hip bone or by mobilizing hematopoietic stem cells from bone marrow to blood. Mobilization can be done with the help of hematopoietic growth factors, most often granulocyte colony stimulating factor (G-CSF) given subcutaneously. The growth factors most likely influence adhesion molecules on the stem cells and bone marrow stroma allowing the stem cells to release into the blood stream. Because of this technique, it has become common to refer to stem cell transplantations instead of bone marrow transplantations as it reflects both methods of harvesting stem cells.   

Harvesting from bone marrow

For extraction of stem cells from bone marrow, the tissue-compatible donor is given general anesthesia and lies in the prone position. Bone marrow is aspirated by repeated punctures of the hip bone. The procedure lasts 1 hour on average. The aspirated bone marrow with the stem cells is transferred to blood pouches with heparin. From the donor, 2 x 108 per/kg body weight of nuclei-containing cells are transferred to the recipient.  

Harvesting from blood

Harvesting stem cells from blood does not require anesthesia, but the procedure can be time-consuming. The stem cells are harvested from a peripheral vein with the help of leukapheresis machines.

Each leukapheresis requires many hours. It is necessary to have 1-3 leukaphereses and a minimum of  2 x 106 CD34 of positive cells per/kg body weight of the recipient.

There are indications that the use of stem cells from blood can lead to quicker hematopoietic reconstitution than stem cells from bone marrow. 

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