Children’s Memorial Health Children’s Memorial Health Institute’s experience in Institute’s experience in

management of PID patients management of PID patients qualified for haematological stem qualified for haematological stem

cell transplantationcell transplantation

Beata Wolska – KuśnierzBeata Wolska – KuśnierzDepartment of ImmunologyDepartment of Immunology

CMHI, Warsaw, PolandCMHI, Warsaw, Poland

Prague May 2006

Complement deficiencies

2%

Others4%

Humoral deficiencies

58%

T cell and combined

deficiencies26%Phagocytic

deficiencies10%

Primary Immunodeficiencies Primary Immunodeficiencies in CMHI registry in CMHI registry

19801980 –– 20020066n n == 912 912

2005- Polish National Registry within ESID Online Registry

Absolute indications for HSCT:Absolute indications for HSCT:

severe combined immunodeficiencies severe combined immunodeficiencies

death before 2nd year of age in natural course death before 2nd year of age in natural course of PIDof PID

Realtive indications for HSCTRealtive indications for HSCT : :

increasing PID number for HSCT as alternative increasing PID number for HSCT as alternative

treatmenttreatment

individual qualification based on:individual qualification based on:

PID typePID type

clinical courseclinical course

HSCT donor availabilityHSCT donor availability

age of patientage of patient

social and psychological aspectssocial and psychological aspects

Realtive indications for HSCTRealtive indications for HSCT

Wiskott-Aldrich syndromeWiskott-Aldrich syndrome ( trombocytopenia, infections, risk of ( trombocytopenia, infections, risk of

malignancies )malignancies )

Hiper IgM syndromeHiper IgM syndrome ( infections, liver insufficieniency – ( infections, liver insufficieniency –

Cryptosporidial Cryptosporidial infection – cholangitis scleroticans, high risk of infection – cholangitis scleroticans, high risk of malignancy )malignancy )

Chronic granulomatous diseaseChronic granulomatous disease ( infections, chronic pulmonary disease )( infections, chronic pulmonary disease )

Others PID :..... DNA breakage disorders.....?????Others PID :..... DNA breakage disorders.....?????

1968 – HLA discovery1968 – HLA discovery

1968 – first bone marrow 1968 – first bone marrow transplantation transplantation

from sibling donors in SCID from sibling donors in SCID

and WAS patientsand WAS patients

1997 – first haploidentical BMT in SCID 1997 – first haploidentical BMT in SCID

patient in Poland – BMT Unit patient in Poland – BMT Unit

WroclawWroclaw

HSCT in PID’sHSCT in PID’s - 29 patients - 29 patients

65%

SCIDCIDCD4limfHIMWASCGDagran

41%59%

BM- 12

PBPC - 17

28%

24%35%

MRD - 7

haplo- 8

MUD - 14

PID typePID type Number of patients

Severe combined immunodeficiencies Severe combined immunodeficiencies ( SCID )( SCID )

18

Combined immunodeficiency ( CID )Combined immunodeficiency ( CID ) 1

Primary CD4 lymphopenia ( CD4 limf )Primary CD4 lymphopenia ( CD4 limf ) 1

Hiper IgM syndrome ( HIMS)Hiper IgM syndrome ( HIMS) 3

Wiskott – Aldricha syndrome ( WAS )Wiskott – Aldricha syndrome ( WAS ) 4

Chronic granulomatous disease ( CGD)Chronic granulomatous disease ( CGD) 1

Severe agranulocytosisSevere agranulocytosis 1

79%

25% boys - 23

girls - 6

Age of patients on HSCTAge of patients on HSCT

11%

37%

52%

< 2 r.ż. - 20

2 - 5 r.ż. - 7

> 5 r.ż. - 2

age of patients in months

024487296

120

mediana 14 months 3 months12 months

InitialsInitials SexSex Date of birthDate of birth Year of diagnosisYear of diagnosis DiagnosisDiagnosis HSCTHSCT OutcomeOutcome

MLML FF 1985-11-031985-11-03 19861986 SCIDSCID NoNo DiedDied

SESE FF 1986-11-241986-11-24 19871987 SCIDSCID NoNo DiedDied

MKMK FF 1994-11-091994-11-09 19951995 SCIDSCID NoNo DiedDied

PM M 1995-07-18 1996 SCID 1997 Alive

MJMJ MM 1996-04-281996-04-28 19961996 SCIDSCID NoNo DiedDied

EBEB FF 1997-03-071997-03-07 19971997 OSOS NoNo DiedDied

KK KK MM 1997-10-241997-10-24 19981998 SCIDSCID YesYes AliveAlive

SUSU MM 1997-12-251997-12-25 19981998 SCIDSCID YesYes AliveAlive

DSDS MM 1998-09-231998-09-23 19981998 SCIDSCID YesYes AliveAlive

MTMT FF 1998-11-191998-11-19 19981998 OSOS NoNo DiedDied

KKKK FF 1999-03-081999-03-08 19991999 OSOS YesYes DiedDied

MDMD MM 1999-07-041999-07-04 20002000 SCIDSCID NoNo DiedDied

LWLW FF 2000-03-142000-03-14 20002000 SCID SCID YesYes AliveAlive

MKMK MM 2000-11-062000-11-06 20012001 SCID SCID YesYes AliveAlive

DSDS FF 2001-01-252001-01-25 20012001 SCID SCID YesYes DiedDied

SKSK MM 2001-04-012001-04-01 20012001 OSOS YesYes Alive Alive

ASAS MM 2001-04-162001-04-16 20012001 SCIDSCID NoNo DiedDied

KJKJ MM 2002-01-092002-01-09 20022002 SCID SCID YesYes AliveAlive

GSGS FF 2002-01-082002-01-08 20022002 SCID SCID YesYes AliveAlive

FWFW MM 2002-07-262002-07-26 20032003 SCIDSCID YesYes AliveAlive

MSMS MM 2002-12-302002-12-30 20032003 SCID SCID YesYes AliveAlive

SDSD MM 2003-06-072003-06-07 20032003 SCIDSCID YesYes Alive Alive

JPJP FF 2004-09-132004-09-13 20042004 SCIDSCID YesYes Alive Alive

MNMN FF 2004-07-012004-07-01 20042004 OSOS YesYes AliveAlive

DWDW MM 2004-03-032004-03-03 20042004 SCIDSCID NoNo DiedDied

WWWW FF 2004-03-252004-03-25 20042004 SCIDSCID YesYes AliveAlive

GNGN MM 2005-10-212005-10-21 20052005 OSOS YesYes Died Died

27 patients:27 patients:

21 SCID / 6 OS21 SCID / 6 OS

OUTCOMEOUTCOME

9 died before HSCT9 died before HSCT

3 died after HSCT3 died after HSCT

15 alive after HSCT15 alive after HSCT

Causes of Causes of deaths deaths

before HSCT:before HSCT:BCG itis – 3BCG itis – 3

CMV – 3CMV – 3

P.carini - 1P.carini - 1

Aspergillosis - 2Aspergillosis - 2

SCID

Follow up of 18 SCID patients after Follow up of 18 SCID patients after HSCTHSCT

315

follow up > 6months

deaths

0

24

48

72

96

120

mo

nth

s af

ter

HS

CT

Causes of deaths Number of patients

GvHD IVst.GvHD IVst. 11

SepsisSepsis 11

Renal insufficiencyRenal insufficiency 11

median 35,9 monthsmedian 35,9 months

Follow up of patients other than SCID after Follow up of patients other than SCID after HCSTHCST

Combined immunodeficiency Combined immunodeficiency ( CID )( CID )

1 patient1 patient

1 -died 2 weeks afer HSCT liver insufficiency

Primary CD4 lymphopenia ( CD4 Primary CD4 lymphopenia ( CD4 limf )limf )

1 patient1 patient

1 - alive and well

Hiper IgM syndrome ( HIMS)Hiper IgM syndrome ( HIMS)

3 patient3 patient1 - alive and well1 - died 2 weeks after HSCT –GvHD1 - graft rejection, expecting second procedure

Wiskott – Aldricha syndrome Wiskott – Aldricha syndrome ( WAS )( WAS )

4 patient4 patient

2 - full PID correction 1 - partial PID correction, neurological sequelae1- gratf rejection, expecting second transplant

Chronic granulomatous disease Chronic granulomatous disease ( CGD)( CGD)

1 patient1 patient

1- graft rejection

Severe agranulocytosisSevere agranulocytosis

1 patient1 patient1 - died 3 weeks after HSCT – GvHD

Immunological reconstitution Immunological reconstitution in 23 patients in 23 patients

13%

17%

70%full

partial

none

PID PID correctioncorrection

Number Number

of of patientspatients

Donor Donor chimerismchimerism

CCCC MCMC ARAR

fullfull 1616 1010 66

partial partial 44 44

none none 33 33

Thank you very much for Thank you very much for your attentionyour attention