Stem Cell Transplant Unit What A Hematologist Should Know
Brig Ajay Sharma, Prof & Head,Dept Of Clinical Hematology & Center for Stem Cell Transplantation & researchGanga Ram Institute of Postgraduate Med Edu & ResSir Ganga Ram Hospital, New delhi-110060
Early or Neutropenic Phase
Day-0 to Day+30Conditioning to Engraftment Period
Key factors for causation of infection: Disruption of anatomical barriers
Mucositis/ Ulcers
Vascular devices
Cellular & Humoral Immunodeficiency
Functional Hyposplenia ( TBI)
IST: CTX/Flu
The BMT/SCT Unit
Blood & Marrow Transplantation (BMT) is a unique procedure, which is performed in a similarly unique area- the BONE MARROW TRANSPLANT UNIT.
Unique Features of BMT room:Minimally equipped
Pressurized positively like a space ship
Highly efficient Filters provide uniqueness.
Not much Upgrading in the mechanization of the unit since its inception
In an era of changing Transplant protocols, do we really need a complex BMT unit?
• BMT is becoming an outdoor procedure• Non-myeloablative transplants more common• BMT being done in Non-HEPA filter rooms
• These observations need to re-looked• BMT unit will continue to be an integral part of Transplant
program
BMT: The “Cleanroom Technology”
A room to provide “The Clean Air”
Separates the patient from OUTSIDE AIR
BMT recipient is extremely immuno-compromized , being under a prolonged & deep neutropenia- a key risk factor for the occurrence of an exogenous infections.
“Cleanroom technology” is defined by 3 Factors:Number of particles present in the air,
Size of particles &
Concentration of Micro-organisms in the room
BMT Rooms were developed in late 19th century
HEPA Filters were adopted in BMT much later…Started as efficient filters in early 20th century.1930: First HEPA filter developed to protect GAS masks of Swiss Army in World War II.
Similar filters were used in German army hospitals to provide clean air inside radiation treatment centers.
Gradually HEPA filter technology was adopted in hospital environment
Cleanroom Technology : History
HEPA Filter
The High Efficiency Particulate Air filter is the main Component of a BMT unit.
Has 3 Layers of filters:Pre-Filter: A fine filter of Class F-5 to F-7Basic Filters :
Can filter up to 3 micro meter
Provides 99.97% efficiency for removing particles >0.3micrometer in diameter.
Filters work on the principle of air exhanges under pressurized flow.
Positive Vs Negative Pressure Rooms
Clinical Use Pos Pressure Room: Neg Pressure : (BMT) (Isolation Room)
Both Rooms are equipped to provide filtration of <0.3 microns with an 99.7% efficiency
BMT Unit: “Water” HygieneMay be as much or even much more hazardous than air pollution.
Water coming from healthcare centers should meet the drinking water requirements???
Even clean water is not optimal for these patients :Microbial infectious agents that are safe for Healthy persons, but not for BMT patients.Water distribution system gets contaminated by
Filamentous fungiGm Neg non-fermenting bacteria
Humidity further promotes colonization of bacteria & Fungi
Decontamination results must be verified using growth media.
Hence, for a good outcome BMT program, the Quality of BMT unit
1. Should be perfect2. Standardized3. Validated by Accepted norms of Accreditation
BMT Unit: Components
Structure
Water
Air
Sterilization
Ancillary units
Nursing station
CSSD
Linen
Pantry
Irradiation facility
Cryopreservation facility
Bio-safety cabinet
Pharmacy
Step down rooms
Structure
Transplant team should be part of the construction team
Proper designing
Provision for AHU, HEPA & Laminar flow
Corridor/Ante room/ main unit room, wash roomAutomatic Doors Outside viewDesign
Flooring/ walls ceilingSmooth surfaceWashable
Sterilization
Dedicated CSSD
Facilities:Autoclaving: for all eqpt & personal items
ETO: for Non-autoclaving objects/ personal items
UV Ports: each room
Planned schedule for linen sterilization
Sterilization of Staff linen
Nursing Station
Separate changing-cum- retiring room
Rest Room
Store( stationary, disposable, pharmacy)
Emergency Resuscitation Eqpt
Written Protocols & Instructions
Doctor Area
Duty-cum-rest Room
Library & IT
Procedure roomCentral line( Hickman, PICC) dressing
Medication room
Hence, for a good outcome BMT program, the Quality of BMT unit
1. Should be perfect2. Standardized3. Validated by Accepted norms of Accreditation
HEPA Quality Control
Filters should be replaced regularly as per manufacture’s recommendation
Be replaced more frequently in polluted & dusty environment of a city hospital ( construction work/ dusty air)
Filtration Efficiency should be checked frequently to determine the appropriate time for the replacement.
There should be directed flow : Unidirectional flow from Air inlet towards outflow exhaust on the opposite side.
Positive Pressure differential between patient room & corridor should be maintained optimally (= > 2.5Pa)
HEPA QC…
BMT room should be built air tight to prevent infiltration of polluted air from outside carrying spores etc
Constant pressure monitoring be done with alarm system
Should have self closing doors to maintain the constant air pressure gradient.
Uni- directional pressure gradient should be maintained towards corridor & toilet, preventing inflow of the air from these sides
ACs ( window or split type) must never be installed in the BMT room/procedure room/ corridor / toilet.
Air Quality in BMT Unit:A Hype??
Why is it important to maintain so strict protocols about air quality in a BMT unit?
Are we being overcautious?
BMT needs to have a standardized Protocol
o HEPA filtration &/or Laminar air flow is likely to directly impact the transplant outcomes by:
Reducing exposure to environmental fungi ( Aspergillus), thereby, reducing the mortality.Benefit is more likely in Allogeneic setting. The efficacy has not been established in autologous transplants.
The BMT unit models may differ in various centers at different parts of world.
A standardization of the BMT units, BMT procedures & related therapies is therefore, very essential to achieve comparable results.
This has become a more compelling necessity with increasing use of stem cell products from different parts of world through registries
Standardization of BMT unit
It is important to lay certain standard yardsticks to ensure proper conduct of stem cell transplantation all over the world
There were initial attempts of standardization in Europe & USA
But main impetus came towards the end of last century
FACT: Foundation for the Accreditation of Cellular TherapyJACIE: Joint Accreditation Committee of ISCT & EBMTISCT : International Society for Cellular TherapyEBMT: Eropean Group of Blood & Marrow Transplantation
Standardization in BMT Unit: The JACIE Model
( Joint Accreditation Committee of ISCT & EBMT)
Established in late 1990s in Europe
Goal: To harmonize international accreditation system for BMT, based on:
Agreeable Quality Standards
Implementation all over the world to direct stem cell transplantation & research
Based on earlier initiative in USA: FACT: The Foundation for the Accreditation of Cellular Therapy
JACIE Model: International Initiative
Adoption of JACIE accreditation in Europe:Late 1990s to early this century
Present Status: Pan- Europe & expanding to other parts of country
No profit –loss basis
Clinical Benefits : Improving survival
Better education & sharing of knowledge
Is Accreditation detrimental?
Makes Planning difficultCan be sorted out
Increases “red tape” hurdles.More of a fear
Delays establishing of new BMT units
Language barrier internationally
ConclusionsBMT is an ever progressive field..
BMT unit is the main step in it, though it has been most neglected one.
A good state of art BMT unit is the key to a successful transplant program.
A well equipped BMT unit is an essential component of the transplant program
The BMT unit demands would keep changing with changing protocols of pre-transplant changes
But more important is the standardization and accreditation of the whole process.