Lecture 14 - HPCT - Process And Complications Flashcards Preview

Block 4 - Heamatology > Lecture 14 - HPCT - Process And Complications > Flashcards

Flashcards in Lecture 14 - HPCT - Process And Complications Deck (26)
1

Uses of stem cell transplantation

- delivry of high dose chemotherapy for treatment of malignant disease
- generate an allogeneic immune response to tumour cells to eradicate residual disease and prevent relapse
- replacement of defective marrow stem cells
- replace defective immune system
- delivery of intense immunosuppression or generation of new immune repertoire to treat auto-immune disease

2

TErminology of HPCT

- autologous: from self (BM or PB)
- allogeneic - from another individual
- syngeneic - from an identical twin
- matched related donor (25-30%)
- unrelated donor
- haploidentical: share a haplotype

3

Basic process of HSCT

- identify patient
- induce CR or good PR
- Collect stem cells and freeze
- HPCT conditioninc
- stem cell reinfusion
- recovery
- disease restage
- secod transplant

4

Sources of autologous stem cells

- bone marrow harvest
- peripheral blood stem cells
- cord blood

5

Reduced intensity conditioning

- uses less conditioning therapy
- relies upon graft vs disease effect
- permits older patients to have transplants
- does not reduce the risk of GVHD
- does not reduce the risk of opportunistic infection with pathogens
- particularly applicable in diseases of older patients such as myeloma

6

Non myelobablative

- goals: immunosuppression to prevent graft rejection rather than combining immunosuppression with myeloablation
- factors: pace of disease, observation of graft vs malignancy effect, age, comorbidity
- agents: TBI, fludarabine, ATG, melphalan, cyclophosphamide, busulfan

7

Alloogeneic chimerism

- evaluate rejection, monitor engrafment, identify relapse
- methods: cytogenetics, FISH, VNTR, RFLP
- myeloablative: with engrafment
- non myeloablative: weeks to months, Donor leukocyte infusions

8

Sources of allogeneic HSC recap

- related siblings
- other matched relative
- matched unrelated volunteer donor
- unrelated cord blood
- haplo-identical relative

9

Impact of HLA matching on outcomes of unrelated donor transplantation

- mismatchinc at either HLA-A/B/C or DRB1 impacts adversely on GVHD and survival
- single mismatches are associated with significant decrements in survival, multiple mismatches are even worse
- HLA-A mismatches significantly impacts on GVHD
- DP and DQ mismatches dont significantly affect outcome

10

Indications for HSCT: Auto SCT

- myeloma
- NHL relapse or intermediate/high grade
- Hodgkin lymphoma
- Germ cell tumours (chemosensitive)
- Amyloidosis
- AML/ALL
- CML without allo-donor
- auto-immune disorders

11

Indications for AlloSCT

- AML
- ALL
- CML
- NHL: high or low grade
- myelodysplasia
- severe aplastic anemia
- immunodeficiency: SCID
- Hematological disorders: thalassemia, Sicke cell

12

Survival post allo BMT

>16 years, malignant: 10-67%
>16 years, non malignant: 58-67%

13

Summary of trends in BMT

- increase in BMT
- increase in all types of BMT
- increase in age of people having BMT
- increase in PB as a source
- increase in survival
- increasing equivalence in outcomes: RD vs UD, MAT vs RIC vs haploidentical tranplant

14

Survival patterns with BMT

- large early mortality
- plateau in survival between 2-5 years
- good disease better than advanced disease
- historyically RD better than UD

15

Complications of HPCT

- predictable
- chronological series
- dependent on a series of variable

16

Graft vs Host disease

- acute and chronic GvHD
- acute GVHD in 30-50%: main determinant of short term mortality GVHD
- Chronic GVHD: 60-80%: main determinant of QOL and of long term survival
- Extensive clinical effects: skin, liver, mouth, eyes, lungs, vagina, joints, fascia

17

GVHD

- high mortality and big impact on QOL
- treatment unsatisfactory: OK if respond to steroids
- prevention: MTX, CSA, Tacrolimus, ATG, MMF
- T cell depletion reduces to

18

Chemo-radiotherapy toxicity
- ATG
- BCNU
- Busulfan
- Cylophosphamide
- Cytarabine (Ara-C)
- Carboplatin/Cisplatin
- Etoposide
- Ifosfamide
- Melphalan
- Thiotepa

- ATG: serum sickness, renal, thrombocytopenia
- BCNU: pneumonitis, VOD, renal, encephalopathy
- Busulfan: pneumonitis, VOD, seizures, rash
- Cyclophosphamide: hemorrhagic cystitis, cardiomyopathy, pneumonitis, histamine
- Cytarabine (Ara-C): mucositis, ataxia, conjunctivitis, hepatitis, rash
- Carboplatin/Cisplatin: renal, ototoxicity, peripheral neuropathy
- Etoposide: mucositis, hypotension, hemorrhagic cysttitis, hepatits
- Ifosfamide: hemorrhaic cystitic, encephalopathy, renal
- Melphalan: mucositis, hepatitis
- Thiotepa: mucositis, rash

19

Infection

- bacterial: pseudomonas, staph
- Fungal: candida, aspergillosis
- Viral: CMV, adenovirus, BK virus, EBV, resp virus
- Prevention: nursing care, hand-washing, isolation, barrier, air filtration, chemoprophylaxis, outpatient transplant, clean diet, vaccination, monitoring and pre-emptive therapy
- treatment: empirical antibiotics, early line removal, secondary prophylaxis

20

Late complications

- predictable
- major cause of toxicity beyond 5 years
- particular problem in children and in those with non-malignant conditions of expected high cure rate
- recent awareness due to establishment of transplant databases
- survivorship
- chronic GVHD, infection, cataracts, Sicca, neuropsychiatric disorders, pulmonary disease, cardiomyopathy, renal disease, endocrine, relapse, secondary cancers

21

Secondary cancers

- relapse
- myeloid malignancies
- PTLD
- high likelihood of secondary cancers
- Skin: BCC, SCC
- Breast x2,2
- Thyroid x3.3
- liver: 8 fold increase risk
- value of screening unclear

22

Endocrinopathies

- pituitary dysfunction
- HTN
- CVD
- Vit D deficiency
- osteoporosis
- hypogonadism
- Dyslipidemia
- Hypothyroidism
- Diabetes
- Hyperthyroid adrenal dysfunction
- Obesity

23

Genital, sexual and reproductive complications of BMT: females

- Genital cGvHD 25-49%
- HPV realted secondary cancer and disease: 13 fold increase
- Ovarian failure 90%
- infertility
- pregnancy 0.6%
- sexual dysfunction 80%

24

Genital, sexual and reproductive complications of BMT: males

- phimosis
- erectile dysfunction
- infertility
- sexual dysfunction

25

The problem of survival post BMT

- 59% risk a chronic health condition by 10 years post BMT
- 3.5x risk of a severe or life threatening condition compared to siblings
- 30% lower life expectancy

26

Psychosocial impacts of BMT

- depression
- anxiety
- panic attacks
- fatigue
- relationship difficulties
- identity concerns
- existential distress
- sexual dysfuntion
- managing uncertainty