Lecture 14 - HPCT - Process And Complications

Question 1

Uses of stem cell transplantation

Answer 1

• 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

Question 2

TErminology of HPCT

Answer 2

• 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

Question 3

Basic process of HSCT

Answer 3

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

Question 4

Sources of autologous stem cells

Answer 4

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

Question 5

Reduced intensity conditioning

Answer 5

• 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

Question 6

Non myelobablative

Answer 6

• 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

Question 7

Alloogeneic chimerism

Answer 7

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

Question 8

Sources of allogeneic HSC recap

Answer 8

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

Question 9

Impact of HLA matching on outcomes of unrelated donor transplantation

Answer 9

• 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

Question 10

Indications for HSCT: Auto SCT

Answer 10

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

Question 11

Indications for AlloSCT

Answer 11

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

Question 12

Survival post allo BMT

Answer 12

> 16 years, malignant: 10-67%

>16 years, non malignant: 58-67%

Question 13

Summary of trends in BMT

Answer 13

• 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

Question 14

Survival patterns with BMT

Answer 14

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

Question 15

Complications of HPCT

Answer 15

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

Question 16

Graft vs Host disease

Answer 16

• 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

Question 17

GVHD

Answer 17

• 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

Question 18

Chemo-radiotherapy toxicity

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

Answer 18

• 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

Question 19

Infection

Answer 19

• 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

Question 20

Late complications

Answer 20

• 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

Question 21

Secondary cancers

Answer 21

• 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

Question 22

Endocrinopathies

Answer 22

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

Question 23

Genital, sexual and reproductive complications of BMT: females

Answer 23

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

Question 24

Genital, sexual and reproductive complications of BMT: males

Answer 24

• phimosis
• erectile dysfunction
• infertility
• sexual dysfunction

Question 25

The problem of survival post BMT

Answer 25

- 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

Question 26

Psychosocial impacts of BMT

Answer 26

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