Stem Cell Transplant Unit

What A Hematologist Should Know

Brig Ajay Sharma, Prof & Head,

Dept Of Clinical Hematology & Center for Stem Cell
Transplantation & research
Ganga Ram Institute of Postgraduate Med Edu & Res
Sir Ganga Ram Hospital, New delhi-110060
Infection is the major factor determining
the outcome in Stem Cell
Transplantation
Early or Neutropenic Phase
Day-0 to Day+30
Conditioning 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
Cleanroom Technology : History
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
Positive Pressure Room ( BMT unit)

Protection from
Air-borne Environmental Microbes
 Negative Pressure Room
( Patient with Airborne Infection)
 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-7
Basic 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.
HEPA Filter is a contrpation of 3 layers
 Max Concentration Limits
& particle size in Isolation Room ( ISO Classification )
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” Hygiene
May 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 fungi
Gm Neg non-fermenting bacteria

Humidity further promotes colonization of bacteria & Fungi

Decontamination results must be verified using growth media.
There may be other
presentations of
BMT unit related
Complications in a
BMT recipient
Hence, for a good outcome
BMT program, the Quality of
BMT unit
1. Should be perfect
2. Standardized
3. Validated by Accepted norms of Accreditation
BMT Unit:
The Considerations….
 BMT Unit: Components
Structure Linen

Water Pantry

Air Irradiation facility

Sterilization Cryopreservation facility

Ancillary units Bio-safety cabinet

Nursing station Pharmacy

CSSD 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 room
Automatic Doors
Outside view
Design

Flooring/ walls ceiling

Smooth surface
Washable
 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 room
Central line( Hickman, PICC) dressing
Medication room
 Attendants’ Area
Rest room

Eating area

Counseling room

Pre transplant visit/work up room

Hence, for a good outcome
BMT program, the Quality of
BMT unit
1. Should be perfect
2. Standardized
3. 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 Therapy

JACIE: Joint Accreditation Committee of ISCT & EBMT
ISCT : International Society for Cellular Therapy
EBMT: 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 difficult
Can be sorted out

Increases “red tape” hurdles.

More of a fear

Delays establishing of new BMT units

Language barrier internationally

 Conclusions
BMT 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.