concept of stem cell transplantation

1. DR.AYUSH GARG
P.G. JR-I
RADIOTHERAPY

2. Definition
Any procedure where hematopoietic stem
cells of any donor and any source are
given to a recipient with intention of
repopulating/replacing the hematopoietic
system in total or in part.

3. Types of Transplant
 Autologous (your own cells)
 Allogeneic
 cells from another person

Sibling

Unrelated Donor

Parent or relative
 or source: Umbilical cord

4. Sources of Hematopoietic
Stem Cells
 Bone Marrow
 PBSC (peripheral blood stem cells)
 Umbilical Cord

5. Best Allogeneic Blood/Bone Marrow
Donor is a brother or sister
 Only 25% of patients are that lucky!
 There is a 1 in 4 chance that any child will
match another child of the same parents
 the formula for knowing whether there is a
donor (1-(3/4)n
)
 In 1% of cases, a parent may be a donor
because of shared HLA types
 Major obstacle in the treatment of
patients who would benefit from an
allogeneic transplant.

8. Bone Marrow
 Standard source of hematopoietic cells
for more than 30 years.
 Transplant physicians may select
marrow because:
 Extensive clinical data are available about
marrow transplant outcomes
 Extensive information is available about
the marrow donation experience

9. Bone marrow transplantation unit

10. Peripheral Blood Stem Cells
 Autologous transplants rely almost
exclusively on PBSC rather than marrow due
to:
 Easier collection of cells
 More rapid hematopoietic recovery
 Decreased costs
 We also use this method in certain instances
for allogeneic transplants in pediatrics.

11. Collection of hematopietic stem
cells
bone marrow peripheral blood

12. Hematopoietic stem cell infusion

13. Umbilical Cord Blood
 Physicians may consider umbilical cord blood
a good choice particularly for patients who
need an unrelated donor and have an
uncommon HLA type or are in urgent need of
a transplant.
 HLA mismatch is better tolerated – even with
haploidentical donors
 Available more quickly than marrow or PBSC
unrelated donors
 Reduced incidence and severity of GVHD

14. Diseases that we transplant in
children
 Autologous
 Relapsed Hodgkins Disease
 Relapsed Non Hodgkins Lymphoma (NHL)
 Stage IV Neuroblastoma
 Relapsed Ewings Sarcoma
 Investigational

Metastatic Ewings Sarcoma

Medulloblastoma, other brain tumors

Autoimmune Diseases (SLE)

15. Allogeneic Transplant
Indications in Children
Malignant Diseases
 AML CR1 – Matched Sibling
 High Risk ALL CR1 (Ph+ ALL)
 Relapsed or Refractory AML or ALL
 Chronic myelogenous leukemia
 Juvenile myelomonocytic leukemia
 Myelodysplastic syndromes

16. Allotransplant for Non-Malignant
Diseases
 Inherited metabolic disorders -
Adrenoleukodystrophy, Hurler syndrome,
metachromatic leukodystrophy, osteopetrosis, and
others
 Inherited immune disorders - Severe combined
immunodeficiency, Wiskott-Aldrich syndrome, and
others
 Inherited red cell disorders - Pure red cell
aplasia, sickle cell disease, beta-thalassemia, and
others
 Marrow failure states - Severe aplastic anemia,
Fanconi anemia, and others

17. Factors influencing the
outcome of HSCT
 Disease factors
 stage
 Patient - related factors
 Age
 Donor - related factors
 Histopompatibility (HLA)
 Sex
 Viral status (CMV positivity)
 Peri-transplant factors
 Conditioning
 GVHD prevention
 Stem cell source and content
 Post-transplant factors


18. Complications
 Allogeneic
 Early

infection

aGVHD

bleeding

toxicity

graft failure
 Late

chGVHD

infection

relapse

gonadal failure

secondary malignancy

toxicity
 Autologous
 Early

infection

bleeding

toxicity
 Late

relapse

infection

gonadal failure

secondary malignacy

toxicity

19. Harvesting Stem Cells
 Adult stem cells obtained by large volume marrow
biopsy/aspiration (1-2L)
 Cord blood stem cells obtained at delivery by sterile
emptying umbilical cord and placenta into blood
donation bag
 Increasingly obtained by processing of peripheral
blood of patients and healthy donors
 Isolated in “real time” from blood after stimulation with
blood cell growth factors
 Stem cells can be frozen for up to 5-10 years

20. Conclusion
 Stem cells can be derived from adult, cord blood and
eventually embryonic stem cells
 Stem cell transplantation can both support highly intensive
chemotherapy and promote highly effective immunotherapy
 Recent advances in stem cell transplantation allow therapy
more tailored to disease and patient
 Improved supportive care measures expand transplant to
more patients
 Expanded applications capitalizing on stem cell plasticity
are feasible

21. THANK YOU

22. Transplant Process (5 steps)
(1) Conditioning,
(2) Stem cell infusion,
(3) Neutropenic phase,
(4) Engraftment phase
(5) Post-engraftment period.

23. Conditioning Phase
 The conditioning period typically lasts 7-10
days.
 The purposes are (by delivery of
chemotherapy and/or radiation)
 to eliminate malignancy
 to provide immune suppression to prevent
rejection of new stem cells
 create space for the new cells
 Radiation and chemotherapy agents differ in
their abilities to achieve these goals.

24. Stem cell processing and
infusion
 Infusion - 20 minutes to an hour, varies
depending on the volume infused. The stem
cells may be processed before infusion, if
indicated. Depletion of T cells can be
performed to decrease GVHD.
 Premedication with acetaminophen and
diphenhydramine to prevent reaction.

25. Stem cell processing and
infusion
 Infused through a CVL, much like a blood
transfusion.
 Anaphylaxis, volume overload, and a
(rare) transient GVHD are the major
potential complications involved.
 Stem cell products that have been
cryopreserved contain dimethyl sulfoxide
(DMSO) as a preservative and potentially can
cause renal failure, in addition to the
unpleasant smell and taste.

26. Neutropenic Phase
 During this period (2-4 wk), the patient
essentially has no effective immune system.
 Healing is poor, and the patient is very
susceptible to infection.
 Supportive care and empiric antibiotic therapy
are the mainstays of successful passage
through this phase.

27. Engraftment Phase
 During this period (several weeks), the
healing process begins with resolution
of mucositis and other lesions acquired.
In addition, fever begins to subside, and
infections often begin to clear. The
greatest challenges at this time are
management of GVHD and prevention
of viral infections (especially CMV).

28. Post-engraftment Phase
 This period lasts for months to years.
Hallmarks of this phase include the
gradual development of tolerance,
weaning off of immunosuppression,
management of chronic GVHD, and
documentation of immune
reconstitution.

29. Graft versus Host Disease (GVHD)
• If donor cells see the host cells as foreign,
the donor cells will attack the host.
• Skin, gut, and liver most likely to be
affected.
• Acute < 100 days after the transplant
• Chronic > 100 days

30.  What are risk factors for GVHD?
 HLA match / mismatch
 Lymphocytes in graft
 Inadequate immune suppression
 Other???

31. Couriel et al, Cancer 2004.
Acute Graft versus Host Disease of Skin

32. Graft Versus Host Disease of the Skin: Grade IV

33. Chronic Extensive Graft versus Host Disease

34. INFECTIONS POST TRANSPLANT

35. Other Problems Encountered
 Hemorrhagic Cystitis
 VOD (venoocclusive disease of the
liver) or SOS (solid organ syndrome)
 Organ Toxicity (lung, heart, kidney)
 Idiopathic Pneumonia Syndrome