Reporting Autoimmune Diseases

in Hematopoietic Stem Cell

Transplantation

Marcelo C. Pasquini, MD, MSc

HVD05_1.ppt

Outline

 Review of autoimmune diseases

(AID).
 Role of transplantation for AID
 Data collection: points to consider.
 AID when present as a comorbidity.

HVD05_2.ppt

Introduction

 AID is a heterogenous group of diseases

that have a link between the immune
system and specific organ damage.
 Spectrum of disease intensities great
impact on quality of life.
 Treatment:
 Immunosuppressive agents:
Ž MMF, CSA, tacrolimus, MTX, Cy
 Immunomodulatory
 Disease Modifying Antirheumatic
Drugs (DMARDs)

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 Classification
 Connective tissue diseases:
 Systemic Sclerosis (SSc)
 Systemic Lupus Erythematous (SLE)
 Rheumatoid Arthritis (RA)
 Juvenile Idiopathic Arthritis (JIA)
 Neurologic
 Multiple Sclerosis (MS)
 Hematologic
 Idiopathic Thrombocytopenic Purpura (ITP)
 Hemolytic Anemia (HA)
 Gastrointestinal
 Inflammatory Bowel Diseases
 Vasculitis
 Wegner Granulomatosis
 Poyarteritis nodosa
 Endocrine
 Diabetes type I
 Thyroiditis

Multiple Sclerosis

 Neurologic AID
 Direct myelin destruction and secondary
oligodendrocytes and axonal damage.
 Symptoms start in early adulthood.
 Variable disease course but most often
progressive
 Estimate that 50% of patients with MS
will not able to walk within 15 years of
onset.

MS Clinical Course

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 MS Clinical
Evaluation

 Diagnosis:
“Dissemination of
time and space”
 Performance of
activities
 MRI evaluation
 CSF:
 Oligoclonal
banding

Multiple Sclerosis

 Diagnosis Criteria (Poser)

 Two attacks and clinical evidence
of two separate lesions or one
lesion and other clinical sign of
the disease
 Symptoms:
 Multifocal neurologic deficits
 Treatment:
 Interferon, antibodies,
corticosteroids.

Systemic Sclerosis (Scleroderma)

 Chronic multisystem disorder of

unknown etiology, characterized by
skin thickening and several visceral
organs.
 Target organs:
 Skin, heart, lungs, GI, blood
vessels, kidneys.
 Two subsets:
 Diffuse cutaneous
 Limited cutaneous

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 SSc Disease Evaluation

 Clinical features
 Skin thickness
 Raynaud’s
 Sclerodactily
 CREST
 Disease markers:
 ANA, Scl-70, ACA
 Evaluation of organ involvement:
 Echo, PFTs, creatinine clearance,
right heart cath, endoscopy

Raynaud’
Raynaud’s Phenomenon

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 Systemic Lupus Erythematous

 Collagen vascular disease with organ

damage by autoantibodies or immune
complexes.
 Women are affected in 90% of cases
 Clinical Manifestation:
 Fever
 Skin rash
 Muskoskeletal (myalgias and arthritis)
 Kidney disease
 Cardiopulmonary
 Hematologic, Neurologic, GI, others

SLE Evaluation

Symptoms and signs

of organ involvement
Presence of autoantibodies or low
complement levels:
ANA, dsDNA, C3, C4

Rheumatoid Arthritis (RA)

 Chronic multisystem disease with

persistent synovitis as the main
characterisitic features
 Women are 3 more affected than
men.
 Symmetric joint involvement
 Other manifestations:
 Rheumatoid nodules
 Vasculitis
 Pleural effusion and lung
nodules
 Neutropenia

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 RA Evaluation

 Number of inflammed
joints
 Rheumatoid Factor
 Radiologic evaluation

Transplantations for AID

 Objective:
 Halt the autoimmunity
process
 Allogeneic
 Graft versus autoimmunity
 Patient population: severe
disease and refractory to
previous therapies

Transplant Indications

 MS:
 Except for primary progressive
 Scleroderma:
 SCOT trial and CTN 0602
 SLE:
 Reduced intensity auto (?)
 RA:
 Frequent post transplant relapses

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 Most Common Diseases Reported to
the CIBMTR
Allogeneic Autologous
N N
Multiple Sclerosis - 74
Systemic Sclerosis 6 56
Systemic Lupus Erythematous 2 14
Idiopathic Thromobocytopenic
Purpura - 4
Rheumatoid Arthritis - 5
Juvenile idiopathic arthritis - 2
Evan’s Syndrome 2 -
Hemolytic Anemia 1 -
Other Autoimmune Diseases 13 7

Data from North and South American Centers

Points in Data Collection

 Similar time points:

 Diagnosis, pre-mobilization, pre-
stem cell infusion, post
transplant follow up.
 Diagnostic Criteria
 Prior Therapies
 Markers of disease activity
 Laboratory and imaging
evaluation
 Evaluation of organ involvement:
Ž PFT, echocardiogram.
 Disease specific scales

Pre-
Pre-TED

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 CIBMTR Disease Inserts

 Recipient Baseline data and

Post-HSCT Data
 MS
 SSc
 SLE
 RA
 JIA

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 Scales and Criteria
 MS
 Expanded Disability Severity Scale
(EDSS)
 Scripps neurological rating scale
 Timed 25-foot walk
 9-hole peg test
 Paced Auditory Serial Addition Test
(PASAT)
 SSc
 Modified Rodnan Skin Score

HVD05_3.ppt

EDSS

 Scale from 0-10 according to the

degree of disability
 O no disability
 3 moderate disability
 5 severe disability but ambulatory
 7 unable to walk beyond 5 meters
 9 bedridden with little interaction
 10 death due to MS

Scales and Criteria

 American College of Rheumatology
diagnostic criteria (RA, SSc and SLE)
 RA:
 EULAR Joint count
 SLE:
 SLE Disease Activity Index (SLEDAI)
 Quality of life and functional Assessments
 SF36
 Health Assessment Questionnaire

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 SLEDAI

Difficulties in Reporting

 Evaluations are less objective

than evaluation of malignant
diseases.
 Different diagnostic criteria
 Several data points for
collection
 Disease status evaluation
relies on different scales

AID as a Comorbidity

 Patients with minimally active

disease at time of
transplantation.
 How the transplant affects the
disease.

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 Case Reports

 Diseases:
 RA, SLE, psoriasis,
myasthenia gravis, MS,
ulcerative colitis, ITP,
Sjogren’s Sydrome
 Most patient received an
autologous HCT
 The majority experience long
lasting remissions.

Recipient Baseline Data

Reporting AID as a Coexisting diseases

 What is relevant collect?

 Patients with active disease
 Patients requiring active
antirheumatic medications
 Why collect?
 Understand the effect of HCT in early
AID
 Understand whether the presence of
AID affects post transplant
outcomes.

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 AID and Transplantation: summary

 Primary indication
 Transplant is the main therapy.
 Patients with more advanced AID
 Coexisting
 Presence as a comorbidity
 Donor with autoimmune diseases
 Adoptive transfer of autoimmunity
 Post transplant chimerism and AID

Conclusion

 HCT for AID is mainly

investigational.
 Reporting data on AID is more
laborious and requires
subspecialties outside the transplant
unit.
 It is important to recognize AID
when present as a comorbidity.

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