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

Infection is the major factor determining the outcome in Stem Cell Transplantation

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

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-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.

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” 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.

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 perfect2. Standardized3. Validated by Accepted norms of Accreditation

BMT Unit:The Considerations….

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

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 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.