Blood and marrow stem cell transplantation A.Basi ADULT HEMATOLOGIST,ONCOLOGIST IRAN UNIVERSITY OF MEDICAL SCIENCES.

Blood and marrow stem cell transplantation

A.BasiA.BasiADULT HEMATOLOGIST ,ONCOLOGISTADULT HEMATOLOGIST ,ONCOLOGIST

IRAN UNIVERSITY OF MEDICAL IRAN UNIVERSITY OF MEDICAL SCIENCES SCIENCES

History

Experiments in the 1950s showed that haemopoiesis could be restored in irradiated animals by engraftment of transfused marrow.

With further understanding of the human leucocyte antigen system, rapid clinical progress was made during the 1970s such that bone marrow transplantation soon became an established treatment for some immune deficiency and malignant diseases.

What is a stem cell transplant?

Transplantation is the reconstitution of the full haemopoietic system by transfer of the pluripotent cells present in the bone marrow (stem cells).

This usually requires prior ablation of the patient’s own

marrow by intensive chemotherapy or chemoradiotherapy.

Subdivided according to the donor source and further

subdivided into the site of stem cell procurement.

AllogenicAllogenic

vs.vs. AutologusAutologus

Bone MarrowBone Marrow

vs.vs.

Peripheral BloodPeripheral Blood

Cord BloodCord Blood

MyeloablativeMyeloablative

vs.vs.

Non- MyeloablativeNon- Myeloablative

RelatedRelated HLA matchedHLA matched

vs. vs.vs. vs.

Unrelated Unrelated HLA mismatchHLA mismatch

Allogeneic transplantation

Profound toxicity of the transplant procedure. Potential recipients should be otherwise healthy

and usually aged <55 years. 1.5 to 5 x 108 nucleated marrow cells per kilogram

are collected for allogeneic transplantation.

Allogeneic transplantation

As bone marrow contains B and T lymphocytes along with macrophages the donor and recipient must be fully or near fully HLA matched to prevent life threatening graft versus host disease or rejection.

Greatest chance of a full HLA match is with a sibling. An average recipient in Western countries has about a 1 in 4 chance [1 – (0.75)n], of having a sibling who is fully HLA matched.

There is also an international registry known as Bone Marrow Donors Worldwide.

Autologous transplantation

Less immunological disturbance occurs in autologous than in allogeneic transplantation.

The stresses on the cardiorespiratory, skin, and mucosal systems, however, are similar.

Autologous recipients therefore should still be otherwise healthy but can be aged up to about 70 years.

In the autologous setting, transplantation of >2.5 x 106

CD34 cells per kilogram, leads to rapid and sustained leads to rapid and sustained

engraftment in virtually all casesengraftment in virtually all cases

Obtaining the graft ( Bone marrow)

Bone marrow is harvested by puncture of the iliac crests under general anaesthesia. It is aspirated directly from the marrow cavity with marrow biopsy needles.

Up to a litre of marrow may be needed to provide sufficient stem cells for transplantation.

Typically, 10–15 mL/kg of marrow is aspirated, placed in heparinized media, and filtered through 0.3- and 0.2-mm screens to remove fat and bony spicules.

Obtaining the graft ( Bone marrow)

The collected marrow may undergo further processing depending on the clinical situation, such as the removal of red cells to prevent hemolysis in ABO-incompatible transplants, the removal of donor T cells to prevent GVHD, or attempts to remove possible contaminating tumor cells in autologous transplantation

Peripheral blood stem cell transplantation

In peripheral blood stem cell transplantation, stem cells are mobilised into the blood by single agent chemotherapy or a haemopoietic growth factor (for example, granulocyte colony stimulating factor), or both.

When the white blood count rises after 5-12 days, the individual is connected to a cell separation machine, blood is drawn off and spun in a centrifuge, and stem cells are harvested while the remaining blood elements are returned to the patient. The procedure takes 2-4 hours and is well tolerated.

Use of peripheral blood stem cells results in more rapid hematopoietic recovery.

Transplantation procedures

Allogeneic VS Autologous

One major procedural difference between allogeneic and autologous transplantation is the requirement for immunosuppression in allografts to prevent graft versus host disease and rejection.

This is achieved with combinations of cyclosporin A and methotrexate or with in vitro or in vivo depletion of T cells using monoclonal antibodies.

Depletion of T cells decrease risk of GVHD but increase risk of relapse due decrease of graft versus leukemia (GVL) or graft versus tumor (GVT) effect.

Outcomes

Outcomes

Sibling matched allograft: five year disease free survival:

Thalassaemia= 90% Chronic myeloid leukaemia= 65% Acute leukaemia= 55% Myelodysplasia= 55%

Outcomes

Autograft: five year event free survival rates Responsive relapsed non-Hodgkin’s lymphoma

=50% Myeloma =25% Relapsed testis cancer= 30%

Procedural complications

Allogeneic and autologous procedures are associated with considerable morbidity and mortality. Overall, transplantrelated mortality :

For autologous recipients is 2-15%, For recipients of sibling HLA matched allografts it

is 15-30%, For recipients of allografts from volunteer,

unrelated donors it is up to 40%.

Procedural complications

Toxicity of conditioning regimenToxicity of conditioning regimen VODVOD GVHDGVHD InfectionInfection Graft failureGraft failure Disease recurrenceDisease recurrence

Infection Prophylaxis in Infection Prophylaxis in Allogeneic Transplant RecipientsAllogeneic Transplant Recipients

Bacterial:Bacterial:CeftazidimeCeftazidime2 g IV q8h while neutropenic.2 g IV q8h while neutropenic. Fungal:Fungal: Fluconazole Fluconazole 400 mg PO qd to day 75 400 mg PO qd to day 75

posttransplant.posttransplant. Pneumocystis carinii :Pneumocystis carinii :Trimethoprim-sulfamethoxazoleTrimethoprim-sulfamethoxazole1 1

double-strength tablet PO bid 2 days/week until day 180 or double-strength tablet PO bid 2 days/week until day 180 or off immunosuppression.off immunosuppression.

Herpes simplex:Herpes simplex: Acyclovir Acyclovir 800 mg PO bid to day 30.  800 mg PO bid to day 30.   Varicella zoster:Varicella zoster: Acyclovir Acyclovir 800 mg PO bid to day 365.  800 mg PO bid to day 365.   Cytomegalovirus:Cytomegalovirus: Ganciclovir Ganciclovir 5 mg/kg IV bid for 7 days, 5 mg/kg IV bid for 7 days,

then 5 (mg/kg)/d 5 days/week to day 100.then 5 (mg/kg)/d 5 days/week to day 100.

Graft versus host disease

Graft versus host disease

The mainstay of treatment remains immunosuppression (cyclosporin, prednisolon).

But severe disease resistant to immunosuppressive therapy is usually fatal