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

Lecture 14 - HPCT - Process And Complications Flashcards

1
Q

Uses of stem cell transplantation

A
  • 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
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2
Q

TErminology of HPCT

A
  • 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
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3
Q

Basic process of HSCT

A
  • identify patient
  • induce CR or good PR
  • Collect stem cells and freeze
  • HPCT conditioninc
  • stem cell reinfusion
  • recovery
  • disease restage
  • secod transplant
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4
Q

Sources of autologous stem cells

A
  • bone marrow harvest
  • peripheral blood stem cells
  • cord blood
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5
Q

Reduced intensity conditioning

A
  • 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
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6
Q

Non myelobablative

A
  • 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
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7
Q

Alloogeneic chimerism

A
  • evaluate rejection, monitor engrafment, identify relapse
  • methods: cytogenetics, FISH, VNTR, RFLP
  • myeloablative: with engrafment
  • non myeloablative: weeks to months, Donor leukocyte infusions
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8
Q

Sources of allogeneic HSC recap

A
  • related siblings
  • other matched relative
  • matched unrelated volunteer donor
  • unrelated cord blood
  • haplo-identical relative
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9
Q

Impact of HLA matching on outcomes of unrelated donor transplantation

A
  • 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
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10
Q

Indications for HSCT: Auto SCT

A
  • myeloma
  • NHL relapse or intermediate/high grade
  • Hodgkin lymphoma
  • Germ cell tumours (chemosensitive)
  • Amyloidosis
  • AML/ALL
  • CML without allo-donor
  • auto-immune disorders
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11
Q

Indications for AlloSCT

A
  • AML
  • ALL
  • CML
  • NHL: high or low grade
  • myelodysplasia
  • severe aplastic anemia
  • immunodeficiency: SCID
  • Hematological disorders: thalassemia, Sicke cell
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12
Q

Survival post allo BMT

A

> 16 years, malignant: 10-67%

>16 years, non malignant: 58-67%

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13
Q

Summary of trends in BMT

A
  • 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
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14
Q

Survival patterns with BMT

A
  • large early mortality
  • plateau in survival between 2-5 years
  • good disease better than advanced disease
  • historyically RD better than UD
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15
Q

Complications of HPCT

A
  • predictable
  • chronological series
  • dependent on a series of variable
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16
Q

Graft vs Host disease

A
  • 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
Q

GVHD

A
  • 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
Q

Chemo-radiotherapy toxicity

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

Infection

A
  • 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
Q

Late complications

A
  • 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
Q

Secondary cancers

A
  • 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
Q

Endocrinopathies

A
  • pituitary dysfunction
  • HTN
  • CVD
  • Vit D deficiency
  • osteoporosis
  • hypogonadism
  • Dyslipidemia
  • Hypothyroidism
  • Diabetes
  • Hyperthyroid adrenal dysfunction
  • Obesity
23
Q

Genital, sexual and reproductive complications of BMT: females

A
  • Genital cGvHD 25-49%
  • HPV realted secondary cancer and disease: 13 fold increase
  • Ovarian failure 90%
  • infertility
  • pregnancy 0.6%
  • sexual dysfunction 80%
24
Q

Genital, sexual and reproductive complications of BMT: males

A
  • phimosis
  • erectile dysfunction
  • infertility
  • sexual dysfunction
25
Q

The problem of survival post BMT

A
  • 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
Q

Psychosocial impacts of BMT

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

Block 4 - Heamatology (23 decks)

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