Hematopoietic stem cell transplantation

- online edition

Emilian Snarski M.D. Ph.D. Ver 2.3 17.11.2015

What is hematopoietic stem cell

transplantation?

Transplantation of hematopoietic cells: medical procedure hinging on collection of such cells (e.g. bone marrow) from the donor, their appropriate preparation ex vivo, appropriate conditioning of the recipient, administration of hematopoietic cells to the recipient and care for the recipient until full restoration of hematopoietic and immune function.

Transplant, graft: hematopoietic: suspension of hematopoietic cells that is being transplanted.

Ola Przybylska 24 days after allotransplantation

(28.11.84)

30 years of Bone Marow Transplantation in

Poland

If you are interested in the history of bone marrow

transplantation please read:

http://transmisja.net.pl/pliki/28.pdf

The publication is a source of many of the

materials shown in the presentation

First attempts of bone marrow

transplantation in the world – King Jan

Kazimierz University in Lvov, third from the

left Jan Raszek.

History of bone marrow

transplantiation in the world 1938 Jan Raszek: first clinical attempts to infuse

marrow cells;

1945 Egon Lorenz and Leon Jacobson: sparing effect of bone marrow on lethally irradiated animals

1963 Georges Mathe: first successful allogeneic transplant in man

1968 Fritz Bach, Robert A. Good, Dirk van Bekkum: first successful HLA-matched allogeneic transplants

1970 E. Donnell Thomas: first successful transplants in leukemia, development of reproducible technology including total body irradiation.

1983 George Santos: development of megachemotherapy.

1979 John Goldman: first successful transplant of cells from the peripheral blood.

1988 Eliane Gluckman: first successful cord blood transplant

1997 Shimon Slavin: first „minitransplantations”

Pierwsze udane przeszczepienie szpiku w Polsce

– profesor Wiesław Wiktor Jędrzejczak

Source: http://www.spcsk.amwaw.edu.pl/node/26

History of bone marrow

transplantation in Poland

1984 Wiktor-Jędrzejczak et al.: First (and first successful) transplantation of allogeneic marrow

1985 Wiktor-Jędrzejczak et al.: First (and first successful) transplantation of autologous marrow.

1996 Hołowiecki et al.: First (and first successful) transplantation of allogeneic marrow from unrelated donor

1998 Lange and Wiktor-Jędrzejczak: First (and first successful) transplantation of allogeneic cord blood.

AUTOLOGOUS HEMATOPOIETIC

STEM CELL TRANSPLANTATION © Wiesław Wiktor Jędrzejczak

Finding Donor

Mobilization

Transplantation

Diagnosis

WBC recovery

Start of GvHD prophylaxis

Timeline

Allogeneic hematopoietic stem cell transplantation

Conditioning

Transplantation medicine family

(everybody should have a donor)…

... 22 000 000 registered unrelated donors are also

avaliable….

© Wiesław Wiktor Jędrzejczak

How do we obtain stem cells for

transplantation?

Source: https://www.youtube.com/watch?v=JIWW4-CTC9I On the movie you can watch the whole procedure

How do we obtain stem cells for transplantation?

Source: http://themscure.blogspot.com On his blog George Goss writes more on his adventures during the bone marrow transplantation

How to prepare a patient to HSCT?

What advantage over standard chemotherapy does

HSCT give?

Autologous HSCT?

Allogenic HSCT?

Procedure of destruction of recipient hematopoietic

system together with its disorders (e.g. leukemia);

Performed using myeloablative cytostatics (busulfan,

melfalan, thio-tepa, BCNU) in myeloablative doses or

total body irradiation (TBI) with a dosis of 1000-1500

cGy usually fractionated.

Myeloablation

Procedure of destroying patient immune system together with its diseases (e.g. autoreactive clone);

Performed using megadoses of cyclophosphamide, purine analogues (fludarabine, 2-CdA), antilymphocytic globulin in combination with cyclosporine A, megadoses of metylprednizolone, and recently also with mycofenolate mofetil.

Immunoablation

BuCy: megachemotherapy

conditioning AD 1984

© Wiesław Wiktor Jędrzejczak

Megachemotherapy BuCy2 AD 2012

AD 2000 prof. Jędrzejczak

thawing of frozen marrow at

the transplant bed directly

prior intravenous injection to

the patient

Bone marrow transplantation =

infusion

Source: http://themscure.blogspot.com On his blog George Goss writes more on his adventures during the bone marrow transplantation

What is the purpose of HSCT?

Medical purpose of HSCT – cure the disease or

prolonge the life of a patient with the best possible

quality

Acute leukemia

Lymphoma

Multiple myeloma

Aplasia

MDS

Autoimmune diseases

And other

What is the advantage of HSCT compared

to chemotherapy or standard drugs?

Natalizumab (AFFIRM study)

Vs HSCT MS (Burt et al. 2009)

przeszczepienie

Multiple Sclerosis

Multiple Sclerosis

Source: https://www.youtube.com/watch?v=KEHgwPmKwBM On her blog Carmel Turner writes about her HSCT for Multiple Sclerosis

Hematopoietic colony in the recipient

marrow 14 days after transplantation

© Wiesław Wiktor Jędrzejczak

What is an ideal bone marrow

transplantation?

Conditioning

Bone marrow transplantation

Regeneration of WBC after two weeks

No complications

Lives happily ever after

Life and BMT are not ideal

Patient has other diseases: diabetes, kidney failure, heart

disease…

Complications of the underlying disease….

Complications of the treatment…

GvHD

Infections: bacterial, fungal and viral

What complications should we prevent?

What complications can we prevent?

How to reduce the complications

Procedures, SOP, procedures,

improvement

Adherence to the procedures

How to make people adhere to the

procedures?

DD Poutsiaka2007 BMT

What if complications of the procedure lead

to the death of the patient?

Medical purpose of HSCT – cure the disease or

prolonge the life of a patient with the best possible

quality

Does it make sense to do hematopoietic stem

cell transplantation?

What the future holds? Predictions AD

2015

Haploidentical transplantation –

we will not need unrelated

donors anymore

Outpatient transplantatin

HSCT in not hematologic diseases

Not direct competition with drugs

What is my dream about transplantation?

We finally achieve what we all longed for.

There is no transplantation. – the CART therapy is

a new promising option in leukemia

The question after watching the movie is simple –

what would happen if we applied this treatment

instead of transplantation?

Hematopoietic stem cell transplantation

- online edition

Emilian Snarski M.D. Ph.D. Ver 2.3 17.11.2015

This is shortened edition of original lecture

If you are interested in topics mentioned here – please follow my blog

www.emiliansnarski.wordpress.com

Or follow first mind-map based hematology textbook

www.hematologiainteraktywnypodrecznik.wordpress.com