What are indications for HSCT in AML?
- CR1: HR patients Therapy-related AML MDS-related AML Primary induction failure Cytogenetics: 7-, del5q, abn (3q) Molecular: FLT3-ITD IR disease with positive MRD after Course 1 - Relapsed AML
Risk factors for acute GVHD (5)
- Related vs unrelated donor
- Degree of HLA mismatch
- Source of stem cells
- Donor sex (female sex associated with more GVHD, proportional to parity)
- TBI-based conditioning
Risk factors for chronic GVHD (5)
- Degree of HLA-mismatch
- Increasing donor age
- Donor sex (female associated with more GVHD)
- TBI-based conditioning
- Previous aGVHD
Risk factors of graft rejection (5)
- Degree of mismatch
- Low cell dose
- Use of T-cell depletion for GVHD prophylaxis
- Underlying conditions: SAA, storage disorders, osteopetrosis (hostile BM)
- (+)ve crossmatch for antidonor lymphocytic Ab
Definition graft rejection
Failure to recover hematopoetic function of stem cell graft (usually caused by recipient T-lymphs)
Risk factors for VOD (6)
- Liver radiation
- Pre-treatment with busulfan, dactinomycin, gemtuzumab
- Prior intensive chemotherapy
- Prior TPN (>30 days)
- Prior iron overload
- Transplant from unrelated donor
Clinical criteria for the diagnosis of VOD
Modified Seattle criteria: otherwise unexplained occurrence of two or more of the following events within 20 days of HCT
●Serum total bilirubin concentration greater than 2 mg/dL (>34.2 micromoles/L)
●Hepatomegaly or right upper quadrant pain
●Sudden weight gain due to fluid accumulation (>2 % of baseline weight)
How to make the diagnosis of VOD?
Often relies on clinical criteria
Doppler US: reversal of flow in portal vein, elevation of mean hepatic arterial resistive index
Diagnosis gold standard= hepatic biopsy, but rarely feasible
List 5 factors impacting the speed of immune reconstitution post-HSCT
- Source of stem cell
- Intensity of conditioning used: Myeloablative < RIC < non-myeloablative
- Presence of GVHD
- Presence of infections
- Age of recipient
Name factors associated with late MDS following autologous HSCT
- Use of etoposide
- Use of TBI-containing regimen
- Amount of chemotherapy received pre-HSCT
- Interval between diagnosis and HSCT
What is the typical time to engrafment in…
… Autologous HSCT?
… Allogeneic HSCT?
7-14 days (autologous)
14-28 days (allogeneic)
Criteria to consider when selecting a donor (6) for allogeneic HSCT?
#1: HLA mismatch Source of stem cell Donor/recipient size mismatch Age and sex of donor Viral infections: CMV status ABO type
Number of cells required for transplant using CURD
TNC: > 3*10^7 cells/kg
CD34+: >3-5*10^6 cells/kg
Degree of match in HSCT:
- What means 6/6?
- What means 8/8?
- What means 10/10?
6: HLA-A, -B, HLA-DR
8: HLA-A, -B, -C, HLA-DR
10: HLA-A, -B, -C, HLA-DR, -DQ
What degree of HLA match is required for a CURD or for a matched sibling donor?
- HLA-A and HLA-B: antigen level
- HLA-C: optional (often correlates with HLA-B)
- HLA-DRB1: allele level
- HLA-DQ and HLA-DP: optional
What degree of HLA match is required if stem cells come from a unrelated donor, or a related donor (not sibling)?
- HLA-A, -B, -C, HLA-DR: allele level
- HLA-DQ, HLA-DP: optional
Indications for HSCT in CML (3)
- Resistance or failure of TKIs
- Good donor, with strong family preference
- Advanced phase (i.e. blasts 10-19%)
Indications for HSCT in Hodking lymphoma
- Autologous, for relapsed of resistant disease
- Allo can salvage failure after autologous HSCT
Indications for HSCT in non-Hodgkin lymphoma
- LLy: same as ALL
- Relapsed disease; autologous HSCT usually tried first, allo can be used if resistance or relapse after autologous HSCT
(especially useful for ALCL)
HSCT is a part of treatment of which solid tumors?
- High risk neuroblastoma (CR1)
- HR germ cell tumor (CR2)
- HR retinoblastoma
- Controversial: Ewing, relapsed HR Wilms, RMS
HSCT is a part of treatment of which brain tumors?
- Medulloblastoma
- Relapsed CNS germ cell tumors
Steps required for donor of HSCT
- Verify consent
- Absence of other health conditions (e.g. asthma) posing a risk to the donor during procedure
- Screening for infectious diseases (similar to transfusion)
Antibiotic prophylaxis in HSCT?
Recommended for pre-engraftment
Quinolones for all recipients of HSCT
What specific infection has been associated with TBI?
Pneumococcal sepsis (late post-engraftment))
