Hematopoietic Stem Cell Transplant

Question 1

Autologous vs. Allogenic

Answer 1

Auto: pt is the donor

Allo: receives from someone else

Question 2

Autologous Transplant

Answer 2

Used to rescue the bone marrow after myeloablative chemo and radiation given to treat the original disease

Chemo/rad eradicate the cancer, transplant is given so that marrow can recover

Stem collection can be done by growth factor priming followed by apharesis or bone marrow harvest

Used for:

• lymphomas
• acute promyelocytic leukemia (APL)
• germ cell tumors
• ovarian cancers
• neuroblastoma
• some autoimmune disorders

Question 3

Allogenic Transplant

Answer 3

Chemo/radiation make space in the marrow for the graft and eradicates any residual disease

Relies in part on the graft’s immune effect on the underlying cancer (graft-versus-leukemia effect)

Stem cell sources

• Related donor (syngenic - twin, non-twin sibling, haplo matched relative)
• Unrelated donor (if matched, related donor is unavailable)
• Umbilical cord blood (readily available for all because don’t need perfect match - not immunologically active)

Collected by apheresis, bone marrow harvest, umbilical cord blood collection

Indications:

• AML, ALL
• CML, CLL
• MDS
• Myeloproliferative disorders
• inborn errors of metabolism
• SCID
• some anemias

Question 4

Logistics of Transplant

Answer 4

1. Referral and meet with transplant physician.
2. Prepare patient emotionally, socially, financially. Caregiver contract!
3. Obtain informed consent (patient and donor, if applicable).
4. Medical screening: Infectious Disease panel, Pulmonary function testing; EKG, MUGA (heart study); CXR and chest CT, bone marrow biopsy, =/- lumbar puncture. Ideally disease is in remission
5. Obtain Stem cells.
   * *6. Conditioning (chemo/radiation)→ Transplant → Engraftment. Depending on type of transplant, hospitalizations can be from one week to over a month.**
6. Ongoing monitoring for graft failure, infections, and graft vs host disease, other complications.
7. Screening for relapsed disease at intervals of 28 days, 100 days, 180 days, 1 year, 2 years.

Question 5

Conditioning

Answer 5

Myeloablative

• High dose chemo + total body radiation
• All autos are myeloablative by definition

Nonmyeloablative

• lower dose chemo and radiation
• lower comorbidities but may have higher risk of relapse

Question 6

Engraftment

Answer 6

Autos ~10 days

Allos: highly dependent on stem cell source

• Sib: 14-21 days
• Cords: 28 days

Risky period in terms of infection due prolonged neutropenia

Question 7

Complications

Answer 7

Infections - febrile neutropenia, bacteremia, pneumonia, etc. ==> pts are on long term, aggressive antimicrobial ppx

Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS)

• blood clots in microvasculature of the liver
• triad of jaundice, RUQ pain and weight gain (b/c ascites)
• dx with dopper US
• very high mortality

Graft vs host disease

• Acute (before day 100)*
• rash, n/v/d, anorexia, transaminitis, cytopenias
• Chronic (after day 100)*
• dry eyes/mouth, sclerodermas, malabsorption, lungs, genitals, cytopenias, transaminitis, pancreatic insufficiency

Caused by donor T cell activation –> target cell apoptosis
Dx based on what is affected
ppx - immunosuppresion, tx - steroids

Diffuse alveolar hemmorhage

Sudden onset of hypoxia due to diffuse bleeding in lungs
Emergent intubation, dx’d with bronchio-alveolar lavage. Tx with high dose steroids and plt transfusion
Very high mortality (90%)