Principles of Stem Cell Transplantation Notes

Principles of Stem Cell Transplantation

‘bone marrow transplant’

Overview of Stem Cell Transplant (SCT)

• Definition: Stem cell transplantation involves transfusing stem cells to a patient to treat various diseases, including cancers and blood disorders.

• Types of SCT:

  • Autologous: Patient's own stem cells are used. High dose chemo followed by stem cell rescue

  • Allogeneic: Stem cells are sourced from a donor.

Key Steps in Autologous Stem Cell Transplant

1. Pretreatment: Patient receives treatment to mobilize hematopoietic stem cells (HSC) from bone marrow into the bloodstream.

2. Collection: Blood stem cells are collected and separated from the blood.

3. Cryopreservation: Stem cells are frozen until needed.

4. Infusion: Thawed stem cells are infused back into the patient after high-dose chemotherapy, which aims to eradicate the disease.

5. Recovery: Remaining blood is returned to the patient, and the body gradually recovers.

Used in myeloma, lymphome, solid tumours, autoimmune disorders.

Historical Milestones in Stem Cell Transplant

• 1957: First donor stem cell transplant by Dr. E. Donnall Thomas.

• 1960s: Introduction of histocompatibility antigens, which are critical for donor matching.

• 1968: First allogeneic bone marrow transplant from a Human Leukocyte Antigen (HLA) matched sibling.

• 1973: Introduction of the first matched unrelated donor (MUD) bone marrow transplant.

Current Indications for HSCT (as of October 15, 2022)

• Table of Recent Data (from BSBMTCT, 2021):

  • Acute Leukaemia: 831 Allograft, 188 Autograft

  • Chronic Leukaemia: 3 Allograft, 782 Autograft

  • Lymphomas: 834 Allograft, 970 Autograft

  • Plasma Cell Disorders (including Multiple Myeloma): 24 Allograft, 1772 Autograft

  • Solid Tumours: 0 Allograft, 202 Autograft

  • Total: 1699 Allograft, 2840 Autograft, 4539 Overall

Allogeneic Stem Cell Transplant Approach

• Pre-Transplant Conditioning: Involves chemotherapy and/or radiotherapy to make room for new stem cells and suppress the immune system. High dose chemo aims to kill any remaining cancer cells in the patient, as well as make space for stem cells from the donor. Also immunosuppresses the patient.

• After that, donor cells are infused into the patient- sometimes gove GCSF injections to help the donor cells engraft.

• Risk of graft rejection - hla matching - some pts will not be able to find a donor- would then look for cord blood transplants - mroe problematic in adults bc would need a lot of stem cells from umbilical cord.

• The aim is that the patient develops a whole immune system from the donor.

• Immunosuppression: Medications used post-transplant include:

  • Cyclosporine (CsA)

  • Tacrolimus

  • Mycophenolate mofetil (MMF)

  • Methotrexate (MTX)

  • Sirolimus

• Indications: Used primarily for conditions like acute leukaemias, MDS, aplastic anemia, myelofibrosis, lymphomas, etc.

• Only used in certain types of cancer

Donor Selection Algorithm

• Donor Types:

  • Matched Sibling Donor- preferred

  • Matched Unrelated Donor (MUD)

  • =Mismatched Donor

  • =Haploidentical Donor

  • =Umbilical Cord Blood

• As go down , transplants become more risky w bigger risk of rejection.

• If have multiple options, other risk factors are considered eg age of donor etc (younger is better)

After stem cell transplant , patients are followed up for life- at least yearly.

Challenges of the Transplant Process

• Not a Single Event: SCT is a complex, multi-step process with potential challenges at each step.

Pre existing comorbidities, pre transplant conditioning and concomitant medications , immune suppression, infection , graft failure etc.

chance of secindary cancer- risk to anyone who has had chemo/radio before.

Post-Transplant Complications

• Infectious Risks: Patients are at high risk for infections from

  • Viral (managed with aciclovir, letermovir)

  • Bacterial (managed with ciprofloxacin)

  • Fungal (managed with posaconazole)

• Given prophylaxis

• Other Complications:

  • Graft failure- life theratening- pt got not immunity need new donor for emergency rescue transplant.

  • Veno-occlusive disease- can cause liver failure

  • Graft Versus Host Disease (GvHD) - why immunosuprression is given

  • Disease relapse- the more immunosuppression you give, the bigger risk of leukemia coming back.

  • All transplant centres need to report outcomes- eg if pt dies, need to state whether because of disease or complication of transplant.

Graft Versus Host Disease (GvHD)

• Definition: A significant cause of mortality in allogeneic HSCT; occurs when donor T cells recognise the patient as foreign and attack the recipient's cells / organs.

• Can occur at any part of body, but skin and gut most common.

T cells from the graft also attack the patient’s malignant cells= graft vs malignancy

Immunosuppression is used to balance the two to get the best outcome

however, is lead cause of non relapse mortality.

• Mechanism:

  • T cells recognize patient’s cells as foreign

  • Balancing GvHD with Graft-versus-Malignancy (GvM) is critical.

• Treatment of GvHD initial high dose steroid

Veno-Occlusive Disease Overview

• Definition: A condition where small liver veins become obstructed post-transplant.

• Diagnosis Criteria:

• up to 21 days post stem cell transplant

  • Bilirubin levels > 2 mg/L

  • Liver enlargement or pain

  • Weight gain or ascites

• OR

• histological diagnosis up to 21 days post transplant.

Not as common as GvHD

Also a common complication of some chemo drugs used- of pt prev been on chemo, further inc risk post transplant.

• Treatment: Defibrotide 25 mg/kg/day for 21 days.

Note

• The transplant procedure is a lifelong journey with numerous considerations for patient care post-procedure, including managing complications that may arise from immune suppression and pre-existing conditions.