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Hematopoietic Stem Cell Transplant

Definition : it is an infusion of bone marrow from donor to recipient patient


‫هى عملية حقن لنخاع العظم (الخاليا الجزعيه) من معطى لمريض مستقبل‬

:Types
Autologous (self) patient own marrow taken until radiotherapy @chemotherapy – 1
@then re infusion of his marrow

Allogeneic (foreign donor) after cancer therapy we infuse foreign marrow from donor – 2

: ‫انواعه تختلف باختالف مصدر النخاع فهو اما‬

‫ ثم اعطاءه‬0‫ باالشعاع والكيماوى‬0‫ذاتى حيث يتم سحبه من المريض وحفظه لحين االنتهاء من عالج الورم‬ -1
‫للمريض مرة ثانية‬
0‫النوع االخر يتم اخذ النخاع من مريض متبرع ويتم حقنه بعد عالج االشعاع والكيماوى‬ -2

Infection is the first cause of death among allogeneic and first cause of morbidity in
autogenic

‫ لالمراض لمريض زرع‬0‫ هى السبب الرئيسى فى الوفاه لمرضى زرع النخاع من متبرع وهى السبب الرئيسى‬0‫العدوى‬
‫النخاع الذاتى‬

Pre conditioning phase: If any treated health problem we must treat it before
starting cancer therapy like septic focus in the mouth or upper respiratory illness @start
vaccination for family member's @CONTACTS

‫قبل البدء فى عالج الورم نقوم بعالج اية بؤره صديديه خاصة بالفم او امراض الجهاز التنفسى وكذلك بعض‬
‫التطعيمات للمخالطين بفترة مناسبة‬

: Conditioning phase
Period of treating underlying disease up to day of transplantation (Cancer therapy)

Patient at this time has no immunity as by radiotherapy he will has mucocutaneousdefect


(no mechanical barrier) sever neutropenia @ poor cell mediate @humoral immune
response then gradual immune recovery will occur to reachengraftment

‫بعد عالج االشعاع و الكيماوى يتأثر الجلد والغشاء المخاطى ليصبحا مشدودين ورقيقين وبهما تشققات مع نقص حاد‬
0‫ وباقى خاليا المناعة حتى عالمات قبول الزرع لترجع االستجابة المناعية تدريجيا‬0‫فى النيوتروفيل‬

: Engraftment
Period of immune recovery which start from transplantation up to sustained levels of
WBCs to be more than 500 @platelets more than 20,000 in three successive samples

This needs from 6 -84 days with average 22 days

If no use of corticosteroids engraftement will be associated with recovery of


phagocytosis, RES function restored------------ lead to decrease risk of bacterial @fungal
infections

GVHD--------------- in allogeneic may be acute (young) or chronic in adults occur after 40 –


100 days of transplantation

Manifestations
High level of immunoglobulin – 1

Low level of IGg @IGg subclasses @ IGA – 2

Impaired function of RES (reticuloendothelial system) – 3

Poor opsonization – 4

Chronic GVHD recovery need years but if occur the immunity will be improved gradually

Phases of Immune Recovery


Phase 1: ---------------- o – 3o days
From day of transplantation up ti30 days in both typesallogeneic @autologous (pre-
engraftment) --------- neutropenia + defected mucocutaneous barrier -------- Opportunistic
infections by skin – mouth -@ GIT flora--------- Candida – aspiragillous @ herpes simplex
reactivation

Phase 2: ----------------30 – 100 days


Post-engraftment phase – more sever in allogeneic with graft versus host disease (GVHD)

Herpes viruses (cytomegalo virus –CMV) --------- Hepatitis, Pneumonia @Colitis – 1

Asperagillus– 2

Pneumocysticgerovecii - 3
Phase 3: ---------------- more than 100 days
)Late phase) Corticosteroid intake due to chronic GVHD

C.M.V,EBV,VZV (cytomegalo – Epstein bar – varicella zoster) – 1

Community acquired respiratory viruses– 2

Encapsulated bacteria (H –influenza type B - Strept-pneumoni) – 3

Bacterial infections– 1
Occur mainly in the first 100 days (phase 1@2)

- :General recommendations
A –Prevent exposure mainly by hand hygiene
B – Prevent disease
Antibiotic prophylaxis whenever neutropenia present must be given but avoid – 1
Glycopeptides @ follow the resistance pattern

I.V Immunoglobulin if IgG less than 400 mg\d – 2

Colony stimulating factor (GM.CSF) granulocyte –monocyte –colony stimulating – 3


factor given in late phase to prevent bacterial infections mainly encapsulated bacteria as
Chronic GVHD present ------ Antibiotic prophylaxis based on sensitivity of bacteria

Strept. Viridance – 1
It is Flora ----------- so no measures to prevent exposure

Perform any dental treatment needed in the pre-engraftment stageNo prophylactic


Antibiotic but early detection @diagnosis for aggressive treatment to avoid bacteremic
shock due to neutropenia

Strept. Pneumonae– 2
:A – Prevent exposure
By strict application of standard precautions
:B – Prevent disease
Pneumococcal 7-Valent conjugates vaccine – 1

If exposed even vaccinated must give antibiotic prophylaxis in chronic GVHD with low – 2
IgG

H – Influenza type B (HIb)


:A – Prevent exposure
Droplet precaution for suspected patient – 1

Vaccination of pediatric household contacts– 2

If children not fully vaccinated give antibiotic prophylaxis if they exposed to diseased – 3
person and their age less than 4years

B – Prevent disease
doses of conjugate vaccine given at 6 – 12 month after HSCT 3

If the patient exposed give Rifampin if not fully vaccinated

Viral infections
of latent viruses (CMV – Herpes simplex –VZV –
Primary or reactivation
community acquired respiratory viruses (influenza – Para influenza
RSV respiratory sensetial virus – Adenovirus))

Cytomegalo virus – 1
A - Prevent exposure :( avoid body secretions)
Avoid sharing cups – glasses –eating utensils– 1

Sexual relation by condom if discordant partner during immunocompromization – 2

Changing diapers --------- Hand Hygiene – 3


Blood transfusion (if –ve take from –ve) or Leukocytic reduced RBCs seronegative – – 4
Leukcytic reduced platelets

Handling of blood by gloves – 5

Isolation of CMV infected Pt. ---------- Contact isolation until no virus secretion in – 6
urine or saliva

:B - Prevent disease @its recurrent


If seropositive patient or –ve Pt. receive from +ve Pt. --------will be RiskPt. For cytomegalo
activation@infection so we must to put him on CMV disease prevention program until
100 days (phase 2)

:Preemptive strategy
Rapid diagnosis by sensitive test@ immediate treatment with Gancyclovair – 1

Sampling more than one time per week starting from 10th day to 100 day(phase 2)to – 2
detect viraemia or antigenaemia rapidly to start Gancyclovair from the moment of
discovery till the end of day number 100 @for at least 3 Weeks whichever is longer

:E.B.V- 2
:A - Prevent exposure
Safe Hygiene

B - Prevent diseaseNo treatmentup till now so noprevention of disease

Herpes Simplex– 3
:A - Prevent exposure
Avoid sharing cups – glasses – eating utensils – 1

Discordant partner ------- condom used for sex – 2

Contact isolation for primary Mucocutaneous or disseminated herpes – 3

:B - Prevent disease reactivation


Any sero positive patient --------- Acyclovir Prophylaxis from conditioning period up to
engraftment or mucositis resolved whichever is longer (about 30 days after HSCT)
Varicella Zoster Virus– 3
)V.Z.V(
:A - Prevent exposure
Avoid exposure to patient with active VZV or post vaccination rash @isolate them – 1
contact and air born

Vaccinate family members before HSCT conditioning phase (at least 4 weeks) – 2

HSCT recipient with VZV disease should place under contact precaution until crusted – 3
lesion while Air born isolation start from 10th day of exposure up to21st day of exposure if
not given Immunoglobulin @if given we will expand the isolation to 28th day of exposure

:B - Prevent disease
Long term acyclovir prophylaxis for Sero +ve patient to avoid activation for one year - 1
or more in case of cGVH disease due to intake of Immunosupressors

If the patient has rash after exposure ------- I.V Acyclovir for 2 days after the lesion – 2
has been crusted

VZIG(varicella zoster immunoglobulin) must be given to HSCT patient(allogeneic or – 3


autologous) if exposed to patient with shingle , chickenpox or post vaccination rash
withen96 hors of exposure and if exposed again after 3weeks must give another dose
@this program will continue for one year or more in cGVH

Community acquired respiratory Virus – 3


)C.R.V(
Influenza – para-Influenza – Respiratory sensetial virus (RSV) –Adenovirus

:A - Prevent exposure
Awareness for (HCW – Pt. – family) – 1

No visit for any person has upper respiratory infection – 2

Daily Active surveillance for rapid diagnosis, treatment @isolation of detected – 3


patient (contact @droplet)
InfluenzaVaccine for HCW – Family contact persons one year before operation (at - 4
least 6 months) @ 0ne year after or more if the patient has cGVH

HSCT must be vaccinated after 6 months seasonally@ response occur after 2 weeks – 5

whatever the vaccination state in the first year or vaccine before 2 weeks(on – 6
exposure ,unexplained upper or lower respiratory tract infection or outbreak) prophylaxis
Amantadine or remantadine @ vaccination if indicated which must continue till outbreak
lasting

Vaccination for the first time for Pt. age from 6 months to nine years must give 2 – 7
doses separate by one month @vaccine not allowed before 6 month old if outbreaks
before 2 weeks after the second dose give Amantadine or remantadine prophylaxis

:B - Prevent disease
If the Pt. Have any upper respiratory infections before conditioning phase postpone – 1
the operation until treatment of the respiratory illness

Respiratory sensetial virus- 4


R.S.V
Rapidly progress to pneumonia @ viraemia soprompt diagnosis @treatment I.V as fetal.
So any upper respiratory infection-------If diagnosed rapidly treat aggressively specially in
pre-engraftment phase

Fungal Infections
General recommendations
Preventing Exposure
Avoid dust exposure some foods(building construction @renovation, Chicken coops – 1
and caves )occupation involving soil.And Foods that contain molds (Blue cheese )

Preventing Disease
GM –CSF and G- CSF shorten the duration of neutropenia @ decrease the attack rate – 1
of fungal disease
Topical antifungal are not recommended for prophylaxis or surveillance cultures for – 2
asymptomatic HSCT but if symptomatic must be taken

Recommendations Regarding Yeast Infections


Preventing Exposure
No effective method to prevent exposure to Candida because it is normal Flora so may
lead to invasive yeast infections after HSCTPreventing Disease
Allogeneic Recipients should administered Fluconazole prophylaxis to prevent invasive
candida infections during neutropenia (phase 1)

Recommendations Regarding Yeast Infections


Preventing Exposure
Immunocompromisedshold avoid hospital renovation @ construction areas or ensure
that rooms for HSCT patients have an adequate capacity to minimize fungal spore counts
:through use of

HEPA filters– 1

ve pressure inPt. room+ - 2

Correctly sealed rooms (Windows @electrical outlets)– 3

Air change per hour more than 12 -4

Good efficient mechanical barrier to contain area of renovation@ constructions to – 5


avoid Aspergillus species

Environmental cleaning more times than regular during and after renovation@ – 6
construction with care to avoid mold spores exposureRecommendations

Regarding PCP (PneumoCystic Pneumonia)


Preventing Exposure
It is due to reactivation of latent infection among immunocomromised Persons

Standard Precautions should be used with Pt, has PCP

Preventing Disease @Disease recurrence


Prophylaxis should be administered from engraftment until 6
months or more in CGVH
Protozoal @Helminithic infections
TMP-SMZ

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