Transplant Process and Infusion

What is the total amount of cells that can be collected through stem cell harvesting?

4-6 × 10^6 CD 34 cells / kg of recipient’s weight

Minimum is 2 × 10^6 (= million)

• < 1-1.5 mil → result in delay engraftment

• 2-5 mil → ensure successful recovery

• > 5 mil → quicker platelet engraftment

Why does patient experience parasthesia of the mouth and extremities during cell harvesting?

Sodium citrate is added to blood to prevent clotting → binds ionized calcium → hypoglycemia

Ideally, cells are administered within ___ hours of collection

72

Common chemotherapy agents used for cell mobilization

Cytoxan

Cytarabine

Etoposide

Paclitaxel

What are the examples of nonmyeloablative regimen?

TBI

TBI + Flu

What is chimerism?

It is evaluated by testing genetic markers to confirm engraftment and to distinguish the donor from the recipient

Reduced intensity conditioning do not seek to eradicate (1)________

Seek to achieve (2)_____________, which allows (3)_________

(1) tumor cells

(2) immunosuppression

(3) engraftment

Donor Lymphocyte Infusion (DLI)

Can be infused after allo transplant to improve total donor chimerism

The maturity of ____ cells determine how likely GVHD is to occur and also improve engraftment

T cells

Which source of stem cells has the least / most mature T cells?

Umbilical cord / peripheral blood

What is the common regiment for multiple myeloma?

HD Melphalan

What kind of conditioning regimen is required for all autologous transplant?

High-dose intensity

What are the common regimens for lymphoma / acute myeloid leukemia?

BEAM

Busulfan, Etoposide, Cytoxan

TBI

What are the common regimens for replapsed/refractory germ cell tumors?

Carboplatin

Ifosfamide

Etoposide3

Why does TBI has to been given in multiple fractions?

Toxicities increase when given in 1 dose

TBI doses are delivered to which part of the body?

entire body including the CNS and testes

What are the side effects of TBI?

GI

Pulmonary

Cataract

Infertility

Hepatic sinusoidal obstruction syndrome (esp receiving TBI after Cytoxan)

Why can TBI cause hepatic sinusoidal obstruction syndrome?

It consumes glutathione (GSH) activity → reduced the body’s ability to metabolize toxic metabolites → build up in the vessels → cause obstruction

ATG

• Inhibits (1) ____ and (2) _____

• Deplete the residual host (3) ______

• It is a regimen used for (4)________, (5)________

• Needs to be premeditated to prevent (6)_______

• Derived from (7)______ and (8)_______

• Prevent (9) ________ and improve (10) _________

(1) T cells

(2) NK cells

(3) T cells

(4) Aplastic anemia, (5) Sickle cell disease

(6) CRS

(7) horse , (8) rabbit

(9) graft rejection, (10) engraftment

CARMUSTINE

• Crosses the (1)___________ barriers

• Requires (2) ____________________

• Side effects:

  • (3)______________

  • (4)______________

  • DO NOT give with

    • (5)_____________

    • (6)_____________

    • (7)_____________

(1) blood - brain

(2) pre and post hydration

(3) nephrotoxicity

(4) pulmonary toxicity

(5) Busulfan

(6) Ifosfamide

(7) Thiotepa

BUSULFAN

• Metabolized by the (1)_______ and excreted in the (2)_____

• Crosses the (3)_______ barriers

  • Which can cause (4)_________, and requires prophylactic (5)___________ medication

• If given orally, instructs patient to take in on an (6)___________

• It is a potential (7)____________

  • Causes (8)______________

(1) liver, (2) urine

(3) blood-brain

(4) seizures, (5) seizure medications

(6) empty stomach

(7) teratogen

(8) birth defects

CARBOPLATIN

• Excreted in the (1)________

• requires (2)_______ throughout the infusion'

• Side effects:

  • (3)____________

  • (4)____________

  • (5)____________

• Long term side effects:

  • Nonreversible (6)___________

  • (7)_________________

(1) urine

(2) hydration

(3) acidosis

(4) hypernatremia

(5) renal insufficiency

(6) ototoxicity

(7) neurotoxicity (neuropathy)

Ifosfamide can also cause _________

hemorrhagic cystitis

TBI should not be given to children younger than ________

2 years of age

Severe combined immunodeficiency (SCID)

• It is a primary immune deficiency of the (1)__________ immune system

• Stem cell transplant in these patients have a unique goal of focusing on (2)_________ of the lymphocytes

• (3)_________ and (4)________ regimens can be used in these patients

(1) lymphocytes

(2) chimerism

(3) Busulfan

(4) Cytoxan

Severe aplastic anemia

• It is a disease in which an autoimmune reaction occurs, leaving the patient’s bone marrow empty and unable to produce normal immune cells

• It is not malignant

• Matched sibling donors → Flu/Cy/ATG

• Unrelated donors → Flu/Cy/ATG/low dose TBI

Patient should not receive > ____ ml/kg per day of DMSO

1

Why does acute hemolytic reaction happen during transplant process?

What are the severe side effects from this?

What are the management?

Major ABO incompatibility

Major side effects:

• Shock

• Abnormal bleeding

• DIC

Management:

• Stop the infusion

• Maintain hydration

• Give additional blood products

Why do products of RBCs and plasma need to be depleted from the stem cell products?

To reduce the incidence of major and minor ABO incompatibility

Acute Tumor Lysis Syndrome

= (1)_________ EMERGENCY!!!

(2) Why does this happen?

(3) What are the signs and symptoms?

(4) What are the managements?

(1) Metabollic

(2) This happen in patient that has large tumor burden (leukemia/ high-grade lymphoma) or the use of steroids (steroids can use to attack cancer cells)

(3) Signs and symptoms:

• Hyperkalemia

• Hyperphosphatemia

• Hyperuricemia (can form stones in the renal pelvis → ureteral obstruction)

• Hypocalcemia (phosphate binds to calcium)

• Elevated lactate dehydrogenase

• Can cause AKI

(4) Managements: PREVENTION is goal!

• Allopurinol at start (or rasburicase in more severe case)

• Sodium bicarb (the key is to increase the urine pH to greater than 7) / rasburicase

• Dialysis if needed

• For hyperkalemia (LIFE-THREATENING!)

  • Furosemide → IV glucose → IV insulin → sodium polystyrene sulfonate

  • Insulin helps to promote potassium moving into the cells from bloodstream

• Acetazolamide may also be used to alkalized the urine , especially in patients with metabolic acidosis or decreased renal functions

• Nurses should be aware that vigorous urinary alkalization may increase the risk of calcium phosphate precipitation in the renal tubules. Therefore, sodium bicarbonate should be discontinued once the urine is alkalized

Major ABO incompatibility

Donor is type A, B, or AB

Recipient is type O (since they already have the antibodies against A, B and AB)

Minor ABO incompability

Donor is type O

Recipient is type A, B and AB

Microangiopathic hemolytic anemia (MAHA)

(1) What is this?

(2) What are the risk factors?

(3) What conditions can cause MAHA fatal?

(4) How to monitor MAHA?

(1) Caused by the destruction of RBCs as they pass through small blood vessels that are abnormally narrow or have damaged walls → make them ruptures → can cause obstruction

(2) Risk factors:

• TBI

• Tacrolimus / sirolimus (the immunosupressions can injure the vascular wall)

• Cyclosporine

(3)

• Hypertension

• GVHD

• Infection (the inflammation can damage the blood vessel linings and activate clotting pathway)

• Renal failure

(4) Monitor:

• Coombs Test (the result has to read Negative)

• Increase of LDH (it is a marker of tissue and cell damage, esp RBCs0

• Liver/ kidney function

HYPERCALCEMIA in transplant

• (1)___________ are responsible for bone breakdown

• (2)___________ are responsible for reabsorbing calcium to build bone

• (3)____________ invades the bone and cause increased (4)__________ stimulation → cause (5) _________ to be released to the bloodstream.

• (6) What are the diagnostic studies?

• (7) Which diuretics medication can cause hypercalcemia?

(1) Osteoclasts

(2) Osteoblasts

(3) Tumor cells / (4) osteoclasts / (5) calcium

(6) Diagnostic studies

• Correlated serum calcium (CSC) level greater than 10.5 mg/dl

  • Mild hypercalcemia: level > 10.5 → hydration

  • Moderate hypercalcemia: level > 12-14 → hydration, biphosphonates

  • Severe hyprecalcemia: level > 14 → life threatening

• Ionized serum calcium level greater than 5.3 mg/dl

(7) Thiazide diuretics

DIC

1. Causes:

   • Septic shock

   • TLS

   • Acute leukemia

   • Liver failure

   • Vascular injuries

2. Symptoms: hemorrhaging from at least 3 unrelated sites

3. Diagnostic tests:

   • D-dimer elevation

   • Fibrinogen level

     • Fibrinogen is a protein found in blood plasma that plays a crucial role in blood clotting. Produced by the liver

   • PT and INR

4. Treatment:

   • Treat sepsis

   • Transfuse platelet

   • Transfuse cryoprecipitate if fibrinogen less than 50

   • Transfuse plasma for active bleeding

SIADH

• Hallmark sign of SIADH is (1)____________ in patient that has not received any diuretics, has no (2)__________ and has normal cardiac/liver/hepatic function.

• It is a condition where the body secretes too much (3) ______, which causes the kidney to (4) __________

• (5) What are the signs and symptoms?

• Diagnostic studies

  • Na less than (6) ________

  • Serum osmolality less than (7) _______

  • Urine osmolality greater than (8) _______

• Mild hyponatremia can be treated with (9) ___________

• MIld to moderate hyponatremia can be treat with (10) __________ and (11) ___________

• If not successful, pharmacologic therapy with (12) _________ is the typical treatment.

(1) Hyponatremia

(2) edema

(3) ADH / (4) retain water

(5) Signs and symptoms:

• Headache, N/V

• Thirst

• Decreased urine output

• tremors

• Seizures → coma

(6) 136

(7) 270

(8) 100

(9) Fluid restriction of 500cc-1000cc per day

(10) Fluid restriction / (11) furosemide

(12) Demeclocycline (inhibits the action of ADH)

**** It is important to treat SIADH slowly to prevent cerebral edema (due to sudden fluid and electrolytes shifting)

What are the common pathogenic organisms during the early neutropenic phase (day 0-30)?

• Gram-positive bacteria (sinus, respiratory tract)

• Gram-negative bacteria (GI, central catheter origin)

• Herpes Simplex Virus (HSV) reactivation

• Fungal

What are the causes of infection during days 30-100 post transplant?

• The development of GVHD

• Opportunistic infections

  • CMV

  • BK virus

  • Adenovirus

  • PCP (Pneumocystic Jiroverci Pneumonia)

Which medication is used to prevent PCP?

Trimethropim-Sulfamethoxazole (TMP-SMX)

What is the treatment of HSV and VZV?

Acyclovir

What are the treatments for CMV?

• Valganiciclovir

• Ganiciclovir

• Foscarnet

What are the treatments for fungal infections?

• Fluconazole

• Posaconazole

• Voriconazole

• Amphotericin B (requires pre and post hydration / not compatible with NS)

What is the role of IVIG?

• IVIG contains a wide variety of antibodies that can help boosting the immune system’s response to infections

Which blood tests are required before transplant?

1. CBC

2. Electrolytes

3. Liver Function Tests

   • Bilirubin

   • Alkaline Phosphate

   • Alanine transaminase

   • Asparate aminotransferase

4. Pregnancy test

5. Blood Type test (ABO/Rh)

Which Infectious Tests are required before transplant?

1. Hep B/ Hep C

2. HIV Type 1&2

3. CMV

4. Herpes

5. Varicella Zoster

6. Syphilis

7. Human T-cell leukemia virus type 1&2

8. West Nile virus

9. Chagas disease screening

For cardiac test (ECHO), the ejection fraction should be > ____ %

45%

Who can perform an allogeneic donor evaluation?

A physician who is not a member of the transplant team caring for the recipient

Myoablative chemo and auto transplants are used to treat (1)_________ and relapsed (2)________ & (3)_________

(1) Multiple Myeloma

(2) Hodgkin Lymphoma

(3) Non-Hodgkin Lymphoma

What are the regimens for Lymphoma?

• BEAM / BEAM-R

• Carmustine / Etoposide / Cytoxan

Which chemo based is used for CNS Lymphoma?

Thiotepa

• Thiotepa / Busulfan / Cytoxan

• Thiotepa / Carmustine (TT-BCNU)

(1)_________ is the key component of RIC regimen and can be combined with an alkylating agents

Fludarabine

What are alkylating agents?

Binds to cancer cell’s DNA → damages the DNA → prevent the cancer from dividing and growing → cells death

• Busulfan

• Melphalan

• Thiotepa

Which chemotherapies are used to deplete T cells, given with allo transplant to prevent GVHD?

• ATG

• CAMPATH

• Post Cytoxan

_______ after an allo transplant only targets the host’s activated T cells

• Does not affect hematopoiesis and engraftments as stem cells are not targeted

Post Cytoxan

Proteins that found on the surface of cells that play a critical role in the immune system’s ability to recognize and distinguish between self and non self.

HLA molecules

(1) ______ and (2) ______ compatibility are not influenced by each other

(1) HLA

(2) ABO

(1) Can platelet be given if HLA mismatched?

(2) Can platelet be given as ABO incompatible? And why?

(1) Yes

(2) Yes

• Platelets do not carry as mu ch concentration of ABO antigens as RBCs.

• Platelets do not circulate as long as RBCs and tend to be cleared relatively quickly by the immune system → immune system responds less strongly to platelets.

Cryopreserved products should be thawed using a water bath set to at least _______

98.6 F ( 37 C)