Hematology Ch 27 Part 1

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Hematopoietic stem cell transplantation (HSCT) is the therapeutic modality for:

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-leukemias
-lymphomas
-solid tumors
-variety of metabolic and immunologic d/o's

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Allogenic bone marrow SCT-stem cell transplant

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-transplantation of stem cells from genetically different but human-leukocyte-antigen matched (hla-matched) individuals
-siblings or family members

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Autologous bone marrow SCT

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transplantation or infusion of a person's own stem cells
(what dad had)

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(origin and differentiation of hematopoietic stem cells {HSCs})

Rare cells found in:

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-bone marrow
-PB of healthy individuals

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(origin and differentiation of hematopoietic stem cells)

Biologic properties:

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-self-renewal
-multilineage differentiation

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(origin and differentiation of hematopoietic stem cells)

pluripotent stem cells differentiate into:

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-myeloid stem cells
-lymphoid stem cells

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(origin and differentiation of hematopoietic stem cells)

Myeloiod stem cells differentiate into:

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-erythroid cell pathways
-granulocyte-macrophage pathways
-megakaryocytic cell pathways

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(origin and differentiation of hematopoietic stem cells)

Lymphoid stem cells differentiate into:

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-T cells
-B cells
-possibly natural killer cells

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(origin and differentiation of hematopoietic stem cells)

committed progenitor cells-colony forming units (CFUs):

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-further differentiate into mature cells
-lack the property of self-renewal

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(sources of HSCs and types of SCTs)

harvested for clinical use from:

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-BM
-PB
-Umbilical cord blood (UCB)

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(origin and differentiation of hematopoietic stem cells)

fetal BM and liver:

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-rich in SCs, restricted due to ethical issues

*not routinely taken from cadavers

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(allogeneic SCT)

infusion of HSCs:

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-from another individual (donor) into the pt. (recipient)
-historically have used BM as source of HCSs
-Now more common to use PBSCs ( peripheral blood stem cells)

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(allogeneic SCT)

indicated when:

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-disease process involves pt.s own stem cells
-pt. stem cells are inappropriate for transplant

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(allogeneic SCT)

therapy for:

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-acute leukemias
-CML
-AA
-hemoglobinopathies
-immune deficiencies
-metabolic genetic d/o's

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(allogeneic SCT)

3 key factors for success:

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1. adequate numbers of HSCs present in the graft
2. recipient's immune system
3. donor's immune system should tolerate host tissue
*avoid graft-versus-host disease (GVHD)

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(allogeneic SCT)

compatibility:

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immune system's recognition of certain cell markers as "self"

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(allogeneic SCT)

major histocompatibility complex (MHC):

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-most important cell markers for determining in compatibility
-polymorphic system

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(allogeneic SCT)

HLA match requires only that:

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-donor and recipient have compatible
*HLA-A, HLA-B, and usually HLA-DR antigens
-complete match
*graft rejection and GVHD can still occur
-successful transplant
*can occur even with some degree of HLA mismatch

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(allogeneic SCT)

first tested:

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family members

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(allogeneic SCT)

unrelated donors:

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National Marrow Donor Program (NMDP)

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(allogeneic SCT)

Unrelated donor selection based on:

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HLA compatibility with recipient

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(allogeneic SCT)

Before receiving the allogeneic HSC infusion:

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-recipient treated with conditioning chemotherapy and/or total body irradiation
*antitumor effect
*enable recipient to better tolerate donor cells

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(allogeneic SCT)

syngeneic transplantation:

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-use BM or PBSCs from an identical twin
-rare transplant
-could be used for d/o's
*treated by allogeneic or autologous transplant
*exception-genetic diseases that affect both twins
-no risk of rejection or GVHD
-no special immunosuppressive drugs

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(autologous STC)

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SC's collected prior to intensive or myeloablative chemotherapy and/or radiotherapy

{what dad had}

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(autologous STC)

indicated when pt.'s SC's:

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-unaffected by the disease
-underlying disease responsive to high-dose chemotherapy and/or radiotherapy

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(autologous STC)

commonly used for:

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-hodgkin lymphoma
-non-hodgkin lymphoma
-multiple myeloma {what dad had}
-solid organ tumors
*breast, ovarian, and testicular cancers
-Pediatric neoplasms

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(autologous STC)
can be performed if disease involves pt own marrow-

consideration to review in this type of case:

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-age
-underlying disease
-degree of marrow involvement
-response to previous chemotherapy
-donor availability

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(autologous STC)

advantages:

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-not necessary to identify HLA-matched donors
-peritransplant mortality low
-older pt.'s tolerate procedure relatively well

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(autologous STC)

disadvantages

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-graft-versus-leukemia effect not possible
-possibility of neoplastic cells in the stem cell product could cause disease recurrence

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(umbilical cord SCT)

UCB :

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-contains sufficient numbers of HSCs
-provide short term and long term engraftment
-use related and unrelated recipients

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(umbilical cord SCT)

cord blood:

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reconstitute hematopoiesis

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(umbilical cord SCT)

total number of SCs generated

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-adequate for most children
-inadequate for most adult transplant pt.'s

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(collection and processing of HSCs)
Bone Marrow:

Surgical Procedure:

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-marrow taken from posterior iliac crest
-for adequate amount of mononuclear cells
*approx. 1 L of marrow harvested
-if recipient not ABO compatible with donor, marrow can be further processed

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(collection and processing of HSCs)

What is replacing bone marrow collection method?

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peripheral stem cell collection

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(collection and processing of HSCs)
Peripheral Blood:

Stem cells rare in PB
-to increase stem cells in PB for autologous SCT:

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-cytotoxic chemotherapy
-hematopoietic cytokines
-combo of chemotherapy or cytokines
-to increase SC's in PB for allogeneic SCT, give hematopoietic cytokines

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(collection and processing of HSCs)
Peripheral Blood:

Following cytotoxic and cytokine therapy:

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-stem cells in marrow rebound
-mobilized to the PB

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(collection and processing of HSCs)
Peripheral Blood:

SC's collected by apheresis:

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-an automated procedure that uses a blood cell separator
-blood components are separated
-MNC's that contain hematopoietic SCs are collected