19 chronic%20 gvhd[1]

© 2012 APHON 1

APHON/PBMTC’s Foundations of Pediatric Hematopoietic Progenitor Cell Transplantation: A Core Curriculum, 2nd Edition

© 2012 APHON

Hematopoietic Progenitor Hematopoietic Progenitor Cell Transplantation: Cell Transplantation: Chronic Graft-Versus-Host Chronic Graft-Versus-Host DiseaseDisease

Kimberly Thormann Powers, MA RN CPNPKimberly Thormann Powers, MA RN CPNP

© 2012 APHON 2

ObjectivesObjectives

• Define chronic graft versus host disease (cGVHD).

• Identify risk factors for cGVHD.• Discuss cGVHD diagnosis and evaluation. • List the factors associated with poor prognosis in

cGVHD.• Describe cGVHD management and treatment.

© 2012 APHON 3

cGVHD: ProcesscGVHD: Process

• Donor T lymphocytes (graft) attack the immunologically incompetent recipient (host)Damage of host tissues

• Often resembles an autoimmune collagen vascular disease

• Poorly understood

© 2012 APHON 4

cGVHD: TypescGVHD: Types

• Progressive cGVHDExtension of acute GVHD (aGVHD)

• De novo cGVHDWithout preceding GVHD

• Quiescent cGVHDAfter resolution of aGVHD

© 2012 APHON 5

cGVHD: Target OrganscGVHD: Target Organs

• Skin• Oral• Ocular• Hepatic

• Pulmonary• Gastrointestinal (GI)• Gynecological• Musculoskeletal• Immunologic

© 2012 APHON 6

Spectrum of manifestations in cGVHD

© 2012 APHON 7

cGVHD ComplicationscGVHD Complications

© 2012 APHON 8

cGVHD: Risk FactorscGVHD: Risk Factors

• Hematopoietic progenitor cell transplantation (HPCT) related aGVHD Human leukocyte antigen (HLA)

disparity Older donor age Peripheral blood stem cells

(PBSCs) as hematopoietic progenitor cell source

Short-course cyclosporine Donor lymphocyte infusion Female-to-male bone marrow

transplantation (BMT) Unrelated HPCT

• Recipient related Older age Viral infection Number of post-HPCT

transfusions Splenectomy Prolonged steroid

treatment

© 2012 APHON 9

cGVHD: Poor Prognostic SignscGVHD: Poor Prognostic Signs

• Persistent severe thrombocytopenia

• Lichenoid changes on skin histology

• Serum bilirubin >1.2 mg/dl• Progressive onset from

acute to chronic • Karnofsky performance <70%

© 2012 APHON 10

Who Is at Higher Risk of Developing Who Is at Higher Risk of Developing cGVHD?cGVHD?

• Case study1. A 12-year-old boy with AML s/p matched

unrelated donor (45-year-old woman) bone marrow with nonmyeloablative HPCT who has a viral infection after being treated for aGVHD.

2. A 4-year-old boy with MDS s/p matched unrelated donor (30-year-old woman) peripheral blood HPCT with myeloablative conditioning who has never had aGVHD.

© 2012 APHON 11

cGVHD: Incidence cGVHD: Incidence

• 40% in patients receiving HLA-identical sibling HPCT

• >50% in HLA-mismatched related sibling HPCT

• 40% to 60% unrelated HPCT, 70% in patients >50 years

• Greater incidence of cGVHD with PBSCs

© 2012 APHON 12

Skin cGVHDSkin cGVHD

• Most commonly involved organ• Inflammatory changes cause

Sclerodermatous presentationoFibrotic thickeningoLeads to contractures and nerve compression

Lichenoid changes oErythematous raised papular skin rashoMay present with only dryness,

hypo- or hyperpigmentation

© 2012 APHON 13

Skin cGVHD: Clinical ManifestationsSkin cGVHD: Clinical Manifestations

• Itching• Burning• Ulcerations• Erythema• Hyperpigmentation• Hypopigmentation• Atrophy• Loss of sweating

• Pain• Flakiness• Shiny appearance• Vertical ridging and

splitting of the nail beds• Alopecia• Graying hair

© 2012 APHON 14

cGVHD: Sclerodermatous Skin cGVHD: Sclerodermatous Skin InvolvementInvolvement

© 2012 APHON 15

© 2012 APHON 16

cGVHD: Lichenoid Skin ChangescGVHD: Lichenoid Skin Changes

© 2012 APHON 17

© 2012 APHON 18

Healthy Skin Biopsy

cGVHD Skin Biopsy

Skin cGVHD: Diagnostic BiopsySkin cGVHD: Diagnostic Biopsy

© 2012 APHON 19

Skin cGVHD: Nursing AssessmentSkin cGVHD: Nursing Assessment

• Assess forAltered integrityAltered body imageNail integrityMonitor for infection

© 2012 APHON 20

Skin cGVHD: Nursing ManagementSkin cGVHD: Nursing Management

• Promote skin care• Administer hydrating lotions, pain medications,

antibiotics, and topical medications• Give immunosuppressant therapy and obtain

drug levels as indicated• Use clear nail polish to strengthen nails and

prevent breakage• Encourage frequent nail care• Consult dermatology• Educate on sun damage and use of sunscreen • Promote range of motion (ROM) exercises• Support the altered body image and give

multidisciplinary team support

© 2012 APHON 21

Oral Mucosa cGVHDOral Mucosa cGVHD

• Changes range from erythema to lichenoid eruption to ulceration

• Xerostomia • Associated infection is frequent• Commonly misdiagnosed as oral candidiasis

© 2012 APHON 22

Oral Mucosa cGVHDOral Mucosa cGVHD

Oral cavity 1 Oral cavity 2

Oral cavity 3 Oral cavity 4

© 2012 APHON 23

Oral Mucosa: Nursing Oral Mucosa: Nursing AssessmentAssessment• Assess for

IntakeAltered tasteAnorexiaIncreased sensitivity to

acidic or spicy foodsOral painOral infections Ability to open the mouth

© 2012 APHON 24

Oral Mucosa cGVHD: Nursing Oral Mucosa cGVHD: Nursing ManagementManagement

• Provide steroid rinses as indicated

• Instruct patient and family on dental hygiene

• Assist with mouth care• Educate regarding dietary

recommendations• Consult dental and nutrition

© 2012 APHON 25

Ocular cGVHD: Clinical ManifestationsOcular cGVHD: Clinical Manifestations

• Incidence of ocular cGVHD in those with cGVHD: 65% to 80%

• PresentationInitially, may have

excessive tearingBurning or gritty sensationSicca syndromePhotophobiaCorneal abrasionsPseudomembrane formation

may lead to blindnessKeratitis and scarring may occur

© 2012 APHON 26

Ocular cGVHD Ocular cGVHD

Lymphoplasmacytic infiltrates around ductal structures of lacrimal glands

© 2012 APHON 27

Schirmer’s TestSchirmer’s Test

© 2012 APHON 28

Ocular cGVHD: Nursing AssessmentOcular cGVHD: Nursing Assessment

• AssessAbility for eyes to tearNeed for preservative-free

artificial tearsVision changesPain or gritty sensation

© 2012 APHON 29

Ocular cGVHD: Nursing ManagementOcular cGVHD: Nursing Management

• Assist and instruct family with ophthalmic medication

• Give immunosuppressants Obtain indicated levels

• Prepare patient and family for Schirmer’s test

• Educate the patient and family• Discuss therapeutic treatment

: drops/ lubricationsPunctal plugsSuturesProtective lenses

© 2012 APHON 30

• May have few relatively mild symptoms until cGVHD hepatic disease becomes severe Jaundice Mild hepatomegaly Abnormal coagulation Elevated alkaline phosphatase Elevated transaminases Elevated bilirubin• Rule out infectious etiology

Hepatic cGVHDHepatic cGVHD

© 2012 APHON 31

Liver: Diagnostic BiopsyLiver: Diagnostic Biopsy

Healthy Hepatic Biopsy

cGVHD Hepatic Biopsy

© 2012 APHON 32

Hepatic cGVHD: Nursing Hepatic cGVHD: Nursing AssessmentAssessment• Assess

JaundiceHepatic sizeRight upper quadrant painSkin irritation associated with hyperbilirubinemia

© 2012 APHON 33

Hepatic cGVHD: Nursing ManagementHepatic cGVHD: Nursing Management

• Administer immunosuppressants.

• Avoid hepatotoxic agents.• Send necessary laboratory

tests.• Prepare for diagnostic

testing.• Provide skin care.

© 2012 APHON 34

Pulmonary cGVHD: Clinical Pulmonary cGVHD: Clinical ManifestationsManifestations

• 5% to 10% incidence• Range of clinical manifestations and

presentations of pulmonary cGVHDSinusitis Bronchiolitis Obliterans (BO)

syndromeBronchiolitis Obliterans organizing

pneumonia (BOOP)Restrictive pulmonary disease

© 2012 APHON 35

cGVHD: Sinopulmonary cGVHD: Sinopulmonary ComplicationsComplications• Sinusitis

Sicca syndrome• Bronchiolitis Obliterans (BO)

Fibrotic processDyspnea, cough, and/or exercise intoleranceComputed tomograpy (CT) scan:

patchy hyperaeration, bronchial dilation, increased density

• Bronchiolitis Obliterans organizing pneumonia (BOOP)Shortness of breath (SOB), cough, and feverCT scan: peripheral patchy airspace consolidation,

nodular opacities

© 2012 APHON 36

Pulmonary Function Test Pulmonary Function Test (PFT)(PFT)• Ideally obtained at Day 100 and at 3-month intervals with

any new significant air-flow obstruction• Significant airflow obstruction

Defined as a decrease in forced expiratory volume in 1 second (FEV1) by > 10% compared to pretransplant values and the FEV1 is < 80%, with an FEV1/forced vital capacity ratio < 0.7 without response to bronchodilators

• Obtain full PFT when the FEV1 is < 80% of the predicted normal value

• Significant air trapping: a residual volume > 120% or air trapping noted on high-resolution CT scan

• Pulmonary consultation for significant obstructive pulmonary changes

© 2012 APHON 37

Pulmonary cGVHD: Nursing Pulmonary cGVHD: Nursing AssessmentAssessment

• Assess Breath soundsColorDyspneaCoughOxygen saturationActivity intolerance and fatigueInability to complete activities

of daily living (ADL)Infection

© 2012 APHON 38

Pulmonary cGVHD: Nursing Pulmonary cGVHD: Nursing ManagementManagement

• Encourage breathing exercises• Perform pulmonary toilet

as necessary• Prepare for follow-up scans and PFTs• Administer immunosuppressants and

draw appropriate levels

© 2012 APHON 39

Case StudyCase Study

• 13-year-old girl who underwent matched related sibling donor peripheral blood HPCT for AML. She has falling chimerism, and the immune suppression was manipulated. She developed cGVHD of the skin. During the next few months she noticed some SOB with activity and was treated with steroids. Symptoms resolved, and 3 months after all immune suppression stopped, she again had an increase in her SOB and new lichenoid skin findings.

© 2012 APHON 40

Pre-HPCT PFT

PFT evaluation for SOB

FEV1 % predicted 93%

FEV1 % predicted ↓ to 34%

© 2012 APHON 41

Case Study: Radiographic FindingsCase Study: Radiographic Findings

High-resolution chest CT

CXR: Opacities seen in both lung bases and bilateral pleural effusions greater on the left than the right

© 2012 APHON 42

Gut cGVHD: Clinical ManifestationsGut cGVHD: Clinical Manifestations

• Diarrhea• Anorexia• Nausea and vomiting• Abdominal pain and cramping• Wasting syndrome

MalabsorptionWeight lossPoor performance statusProgressive GI symptoms

(early satiety, dysphagia)• Infection

© 2012 APHON 43

Normal Gut Biopsy

cGVHD Gut Biopsy

Gut: Diagnostic BiopsyGut: Diagnostic Biopsy

© 2012 APHON 44

Gut cGVHD: Nursing AssessmentGut cGVHD: Nursing Assessment

• AssessNausea and vomitingDiarrheaPainDysphagiaWeight lossBleedingFluid statusCaloric intake

© 2012 APHON 45

Gut cGVHD: Nursing Gut cGVHD: Nursing ManagementManagement• Test stools for blood• Measure stool output• Administer fluids• Provide nutritional support

EnteralParenteral

• Administer medications ImmunosuppressantsSupportive care agents

• Prepare for diagnostic procedures• Consult nutrition• Educate regarding diet, immunosuppression, and

associated infection

© 2012 APHON 46

Gynecological cGVHD: Gynecological cGVHD: Clinical Manifestations Clinical Manifestations • Vaginal epithelial damage occurs due to cGVHD

InflammationStricture formationNarrowing

• Vaginal sicca• Vaginal atrophy

Leads to painful sexual intercourse• Symptoms may include

InflammationDry vaginaObstruction of menstrual flow

because of strictures

© 2012 APHON 47

Gynecology: Nursing Assessment Gynecology: Nursing Assessment and Managementand Management

• Assess (within the context of normal growth and development)Sexual dysfunctionPainAltered body image Infection

• ManagementConsult gynecologistEncourage use of

lubricantsEncourage discussion of

sexual issuesEncourage

interdisciplinary team management/specialty referral

Administer medications

© 2012 APHON 48

Musculoskeletal cGVHD: Musculoskeletal cGVHD: Clinical Manifestations Clinical Manifestations • The severe damage done by sclerodermatous

skin cGVHD can cause significant musculoskeletal involvement StiffnessContracturesJoint painLimited ROMMuscle crampsCarpal spasmSwellingArthralgias

© 2012 APHON 49

cGVHD: Contractures cGVHD: Contractures

© 2012 APHON 50

Physical Therapy EvaluationPhysical Therapy Evaluation

Therapist objective findings:2-minute walk test: 7 laps (patient not out of breath after test, limited by shoes, wearing sandals with heel)(1 lap = 50 feet)

Grip Strength

Trial Left Right

1 18 kg/40 lb 19 kg/42 lb

2 21 kg/45 lb 20 kg/45 lb

3 20 kg/43 lb 22 kg/52 lb

Dominant hand: rightDynamometer position: 2

© 2012 APHON 51

Physical Therapy Clinician EvaluationPhysical Therapy Clinician Evaluation

ROM is measured for all the joints by physical therapy, but the MD /APN can do a basic evaluation: 1- poor mobility to 7= full mobility

Shoulder2 3 6

Elbow2 4 7

Wrist and Fingers6

Foot Dorsiflexion

2 341

© 2012 APHON 52

cGVHD: Fasciitis and MyositiscGVHD: Fasciitis and Myositis

• Fasciitis Diagnostic sign of cGVHD Skin swelling: skin taut, bound down,

and irregularly thickened, with small depressed areas (orange peel)

Contractures, joint stiffness Pathology: lymphocytic infiltrates,

increase of collagen fibers

• Myositis Distinctive sign of cGVHD Moderate to severe proximal muscle

weakness, myalgia, fever, contracture, and skin induration

Elevated creatinine phosphokinase and aldolase enzyme

Pathology: degeneration, necrosis, and regeneration of muscle fibers

© 2012 APHON 53

Musculoskeletal: Nursing Musculoskeletal: Nursing Assessment and ManagementAssessment and Management

• AssessPerformance scoreAbility to perform ADLPainROMMonitor for signs and

symptoms of physiologic dysfunction

Monitor for bone damage

Nutritional status

• ManagementPrepare for diagnostic

testsConsult rehabilitation

services Consult orthopedicsAdminister

medicationsCollaborate with

interdisciplinary team

© 2012 APHON 54

Physical Therapy: Evaluation Report Physical Therapy: Evaluation Report

Summary: patient reports functionally ↑ endurance. Low 2-minute walk test d/t patient’s choice of footwear and self-selected pace. Educated patient on gastroc stretch and reviewed importance of hydration to prevent cramping.

GOAL TIME FRAME MET COMMENTS

Will report no cramps with activity

Goal to be met 1 session from 7/9/2010

No New goal

Will increase 2-minute walk to 8

Goal to be met 1 session from 7/9/2010

No New goal

Follow-up: continue to see patient at each clinic visit, every 2 weeks

© 2012 APHON 55

Immune System: Clinical Immune System: Clinical ManifestationsManifestations• cGVHD is immunosuppressive,

and cGVHD treatment is further immunosuppressive, resulting inFunctional asplenia Variable immunoglobulin G (IgG) levelsOpportunistic infectionsCytopenia (thrombocytopenia)

© 2012 APHON 56

cGVHD: Infection RiskcGVHD: Infection Risk

• AssessSigns and symptoms

of infectionRelative risk of

infectionHome environmentSchool reentry

• ManagementAdminister medicationsPrepare for diagnostic

testsObtain laboratory workEducate patient and

familyo Immunosuppressive

treatmentAdminister appropriate

vaccines

© 2012 APHON 57

cGVHD: NIH Consensus cGVHD: NIH Consensus Scoring CriteriaScoring Criteria

• cGVHD is defined by the presence of at least one distinctive

manifestation with support by histologic, radiologic, or laboratory

evidence or diagnostic clinical sign of cGVHD without the features of

aGVHD overlap syndrome where there are features of aGVHD and

cGVHD present

• There is no time limit after stem cell transplant for the diagnosis of any

clinical features

• The differential diagnosis must be ruled out for each system affected

• Clinical score of 0 to 3 for involved sites/organs

© 2012 APHON 58

NIH Consensus: Scoring NIH Consensus: Scoring CriteriaCriteria• Clinically based• Organs/sites assessed/scored

SkinMouthEyesGI tractLiverLungsJoints and fasciaGenitourinary tract

© 2012 APHON 59

NIH cGVHD organ-specific staging From Filipovich, A. H., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 11(12), 945-956. Reprinted with permission of Elsevier.

© 2012 APHON 60

Classification of GVHDClassification of GVHD

Site or Organ Diagnostic Distinctive Other

Skin PoikilodermaLichen planus

ScleroticMorphea like

Lichen sclerosus

Depigmentation Keratosis pilarisHyperpigmentationHypopigmentationSweat impairment

Ichthyosis

GI Esophageal webEsophageal strictureEsophageal stenosis

Exocrine pancreatic insufficiency

Lung BO on biopsy BO by PFT and radiology

Muscles, joints, fascia FasciitisStiff joints

Contractures

MyositisPolymyositis

EdemaMuscle cramps

Arthralgias/arthritis

Mouth Lichen typeHyperkeratosis plaques

Mouth opens less

XerostomiaMucocele

UlcersPseudomembranes

From Filipovich, A. H. et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11(12), 948. Reprinted with permission of Elsevier.

© 2012 APHON 61

NIH Consensus: Scoring CriteriaNIH Consensus: Scoring Criteria

• Scoring0: no manifestations or symptoms1: no significant impairment of function2: significant impairment of ADL and

no major disability3: significant impairment of ADL and

major disability

www.asbmt.org

© 2012 APHON 62

cGVHD: NIH Global cGVHD: NIH Global ScoringScoring• Mild

No significant impairment of functionOnly 1 or 2 organs (except lung)Maximum organ score of 1

• ModerateSignificant impairment but no major disability3 or more organs with maximum score of 1One organ with maximum score of 2Lung score of 1

• SevereMajor disabilityScore of 3 in any organ or siteLung score >2

© 2012 APHON 63

cGVHD: Primary cGVHD: Primary TreatmentTreatment• Systemic treatment

Multiple organs sites affected >3Pulmonary involvementOnset of cGVHD while on steroid therapyProgressive onset Thrombocytopenia

• Initial treatment often employs corticosteroidsSingle agentCombination with calcineurin inhibitor

© 2012 APHON 64

cGVHD: Salvage TherapycGVHD: Salvage Therapy

• Refractory cGVHD treatmentMonoclonal antibodies

o InfliximaboEtanerceptoAlemtuzumab

Polyclonal antibodiesoAntithymocyte globulin

Other agents and modalitiesoThalidomideoHydroxychloroquineoPentostatino Imatinib mesylate (GLEEVEC®)oUltraviolet (UV) radiation

Extracorporeal photopheresis (ECP)

© 2012 APHON 65

Treatment Side EffectsTreatment Side Effects

Agent Class Side effect

Pentostatin Nucleoside analogue Nausea, vomiting, infections, anemia

Etanercept TNF receptor Infections

Imatinib Tyrosine kinase inhibitor, PDGF inhibitor

Myelosuppression, weight gain, hepatitis

Montelukast Leukotriene inhibitor Nausea, headache

Infliximab Anti-TNF-a Hypersensitivity, infections

ECP UV irradiation, 8-MOP Skin hypersensitivity, nausea, bleeding

Sirolimus Macrocyclic lactone Myelosuppression, hyperlipidemia, HUS, TTP, renal impairment, fluid accumulation

© 2012 APHON 66

Extracorporeal Extracorporeal photopheresis (ECP)photopheresis (ECP)

© 2012 APHON 67

What Is Extracorporeal What Is Extracorporeal photopheresis?photopheresis?

The photoactivated white blood cells are returned to the patient

Photoactivation with UVA light

Methoxsalen

White blood cells are treated with methoxsalen and exposed to UVA lightBlood is

separated by centrifugation and red blood cells are returned

The UVAR XTS Instrument draws blood from the patient

© 2012 APHON 68

Extracorporeal photopheresis: Extracorporeal photopheresis: Procedure Procedure

• Procedure 150-300 ml of buffy coat (white cells)

is collected by apheresis Methoxypsoralen (photosensitizing

agent) is added to collection bag Cells are exposed to UV light Infused into the patient Well tolerated

o Hypo- or hypertension may occur

o Fluid shifts

• Research Ongoing to determine length,

regularity, and timing of ECP

© 2012 APHON 69

Before ECP

Before ECP

After ECP

After ECP

© 2012 APHON 70

cGVHD: Pediatric Poor cGVHD: Pediatric Poor Prognostic Signs Prognostic Signs • Recipient age• aGVHD Grade II-IV• Female donor to male recipient• Diagnosis of malignancy• TBI in conditioning

© 2012 APHON 71

cGVHD: The TeamcGVHD: The Team

Family/CaregiversBMT Team

Pharmacy

Medical Consultants

Psychology

Nutrition

Social WorkReferring

Team

Insurance

Child Life

Home Care Company

Nursing Staff

Physical Therapy

© 2012 APHON 72

Quality of Life Issues Facing HPCT Quality of Life Issues Facing HPCT RecipientsRecipients

• Fatigue

• Depression

• Sleep disturbance

• Stress

• Nutrition: weight loss or gain

• Activity and exercise

• Friendships

• Growth and development

• School or work

© 2012 APHON 73

FatigueFatigue

• Symptoms Tired, unable to do what peers

are doing General weakness Unable to concentrate Irritability Lasting months to years

• Management Create schedule with quiet time Encourage routine exercise Get 10 to 12 hours of sleep a night Consider stimulant medication

© 2012 APHON 74

NutritionNutrition

• Symptoms cGVHD increases your calorie needs Encourage well-balanced meals Give healthy snacks throughout the day Increase the protein in the child’s diet Increase fluids to keep well hydrated

• Management Follow up with HPCT team Check dietary restrictions d/t medications May need supplements if diet is not

well balanced May need help creating a diet plan with the nutritionist Follow up with diabetic educator if diabetes from long-term

steroid use

© 2012 APHON 75

DepressionDepression

• Symptoms Sleeping moreLack of energyBody image alteredNoncomplianceEasily agitatedWithdrawnLack of interest in activities

• ManagementPlanned activitiesSchedule breaksTalk to specialistMedications

© 2012 APHON 76

Transitions Transitions

• Transition to schoolSharing information with schoolPreparing student for the transitionPlanning curriculum, educational supportEstablishing connections

• After schoolVocational planning in high schoolGuidance counselor assistance for planning

postsecondary educationSeek colleges and technical schools with learning

support programs

© 2012 APHON 77

Health Maintenance GuidelinesHealth Maintenance Guidelines

• Physical examination with labs• Eye examination• Dental examination • Pulmonary evaluation• Gynecological examination

(if of age)• Physical therapy evaluation with ROM testing• Endocrine evaluation

© 2012 APHON 78

cGVHD: ConclusioncGVHD: Conclusion

• Major cause of morbidity and mortality• Nurse’s role is vital

AssessmentMedicationsTreatmentsEducationProvide comprehensive multidisciplinary

continuity of careoChallenge

© 2012 APHON 79

ResourcesResources

• American Society for Blood and Marrow Transplantation www.asbmt.org

• BMT InfoNet www.bmtinfonet.org

• Candlelighters Childhood Cancer Foundation www.candlelighters.org

• Children and Adults with Attention-Deficit/ Hyperactivity Disorder (CHADD) www.chadd.org

• Children’s Oncology Group www.childrensoncologygroup.org

• CureSearch www.curesearch.org

• Chronic GVHD Learning www.asbmt.org/policystat/policy.htm

• Lance Armstrong Foundation www.laf.org

© 2012 APHON 80

cGVHD: ResourcescGVHD: Resources

• Learning Disabilities Association of America www.ldanatl.org

• Leukemia & Lymphoma Society www.lls.org

• Leukemia Research Foundation www.leukemia-research.org

• National Cancer Institute www.cancer.gov/cancertopics/eatinghint

• National Marrow Donor Program www.nmdp.org

• National Sleep Foundation www.centers.sleepfoundation.org/insomnia/children

• Pediatric Oncology Resource Center www.acor.org/ped-onc/

© 2012 APHON 81

cGVHD: ResourcescGVHD: Resources

• Pediatric Blood and Marrow Transplant Consortium www.pbmtc.org

• Schwab Learning www.schwablearning.org

• Supplementary information and updates www.marrow.org

• Books Educating the Child with Cancer, A Guide for Parents and

Teachers, edited by Nancy Keene. 2003, Candlelighters Foundation

Childhood Cancer Survivors, A Practical Guide to Your Future, Keene, Hobbie, Ruccione. 2000, O’Reilly and Associates

© 2012 APHON 82

QuestionsQuestions

1. What is the most frequently involved organ for cGVHD?

A. Gut

B. Lungs

C. Skin

D. Eyes

E. Liver

© 2012 APHON 83

QuestionsQuestions

2. What treatments would you think of using for cGVHD of the skin?

A. ECP

B. Pentostatin

C. GLEEVEC®

D. Hydroxychloroquine

E. Thalidomide

© 2012 APHON 84

QuestionsQuestions

3. A child with some cGVHD of the skin that is resolving and a lung score of 1 would be rated per the cGVHD global scoring as?

A. Mild

B. Moderate

C. Severe

© 2012 APHON 85

QuestionsQuestions

4. A child with a diagnostic clinical sign of cGVHD with no signs of aGVHD would be rated per the cGVHD global scoring as?

A. Mild

B. Moderate

C. Severe

© 2012 APHON 86

QuestionsQuestions

5. What type of cGVHD comes after a resolution of aGVHD?

A. De novo

B. Progressive

C. Quiescent

© 2012 APHON 87

ReferencesReferences

• Akhtari, M., Langston, A. A., Waller, E. K., & Gal, A. A. (2009). Eosinophilic pulmonary syndrome as a manifestation of GVHD following hematopoietic stem cell transplantation in three patients. Bone Marrow Transplant, 43(2), 155-158.

• Andree, H., Hilgendorf, I., Leithaeuser, M., Junghanss, C., Holzhueter, S., Loddenkemper, C., et al. (2008). Enteral budesonide in treatment for mild and moderate gastrointestinal chronic GVHD. Bone Marrow Transplant, 42(8), 541-546.

• Arora, M., Nagaraj, S., Witte, J., DeFor, T. E., MacMillan, M., Burns, L. J., et al. (2009). New classification of chronic GVHD: added clarity from the consensus diagnoses. Bone Marrow Transplant, 43(2), 149-153.

• Barkholt, L. (2009). Importance of CsA drug monitoring in SCT recipients to minimize GVHD and maximize graft vs. leukemia. Pediatr Transplant, 13(4), 400-403.

• Benson, D. M., Jr., Smith, M. K., Krugh, D., & Devine, S. M. (2008). Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab. Bone Marrow Transplant, 41(6), 595-596.

• Berger, M., Pessolano, R., Albiani, R., Asaftei, S., Barat, V., Carraro, F., et al. (2007). Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report. J Pediatr Hematol Oncol, 29(10), 678-687.

© 2012 APHON 88


• Chiang, C. C., Lin, J. M., Chen, W. L., & Tsai, Y. Y. (2007). Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea, 26(7), 861-863.

• Couriel, D., Carpenter, P. A., Cutler, C., Bolanos-Meade, J., Treister, N. S., Gea-Banacloche, J., et al. (2006). Ancillary therapy and supportive care of chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transplant, 12(4), 375-396.

• Daguindau, E., Lioure, B., Buzyn, A., Robin, M., Faucher, C., Kuentz, M., et al. (2009). Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment. Bone Marrow Transplant.

• Drew, D. Z., Donohue, T., Ramos, C., Cook, L., Goodwin, R., Patronas, N., et al. (2009). Chronic GVHD manifesting as parotitis after allogeneic hematopoietic SCT. Bone Marrow Transplant.

• Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant, 11(12), 945-956.

• Fry, T. J. (2009). Is a little GVHD a good thing? Blood, 113(25), 6274-6275.

© 2012 APHON 89


• Furlong, T., Martin, P., Flowers, M. E., Carnevale-Schianca, F., Yatscoff, R., Chauncey, T., et al. (2009). Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant, 44(11), 739-748.

• Garland, P., Dazzi, F., & Marin, D. (2009). Dasatinib may not suppress the GVL effect of donor lymphocyte infusions for CML. Bone Marrow Transplant.

• Gassas, A., Sung, L., Saunders, E. F., & Doyle, J. (2007). Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia: significantly lower relapse rate in unrelated transplantations. Bone Marrow Transplant, 40(10), 951-955.

• Hausermann, P., Walter, R. B., Halter, J., Biedermann, B. C., Tichelli, A., Itin, P., et al. (2008). Cutaneous graft-versus-host disease: a guide for the dermatologist. Dermatology, 216(4), 287-304.

• Hidaka, M., Iwasaki, S., Matsui, T., Kawakita, T., Inoue, Y., Sakai, T., et al. (2009). Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant.

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• Hovi, L., Kurimo, M., Taskinen, M., Vettenranta, J., Vettenranta, K., & Saarinen-Pihkala, U. M. (2009). Suboptimal long-term physical performance in children and young adults after pediatric allo-SCT. Bone Marrow Transplant.

• Ishaqi, M. K., Afzal, S., Dupuis, A., Doyle, J., & Gassas, A. (2008). Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant, 41(3), 245-252.

• Jacobsohn, D. A. (2008). Shedding some LIGHT on chronic GVHD. Blood, 112(7), 2593-2594.

• Jacobsohn, D. A., Rademaker, A., Kaup, M., & Vogelsang, G. B. (2009). Skin response using NIH consensus criteria vs Hopkins scale in a phase II study for steroid-refractory chronic GVHD. Bone Marrow Transplant.

• Kamble, R. T., Selby, G. B., Mims, M., Kharfan-Dabaja, M. A., Ozer, H., & George, J. N. (2006). Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant, 12(5), 506-510.

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• Kew, A. K., Macaulay, R., Burrell, S., Rubin, S., Dow, G., & Couban, S. (2007). Central nervous system graft-versus-host disease presenting with granulomatous encephalitis. Bone Marrow Transplant, 40(2), 183-184.

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• Magro, L., Catteau, B., Coiteux, V., Bruno, B., Jouet, J. P., & Yakoub-Agha, I. (2008). Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD. Bone Marrow Transplant, 42(11), 757-760.

• Martin, P. J., Weisdorf, D., Przepiorka, D., Hirschfeld, S., Farrell, A., Rizzo, J. D., et al. (2006). National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant, 12(5), 491-505.

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• Mohty, M., Marchetti, N., El-Cheikh, J., Faucher, C., Furst, S., & Blaise, D. (2008). Rituximab as salvage therapy for refractory chronic GVHD. Bone Marrow Transplant, 41(10), 909-911.

• Nakasone, H., Ito, A., Endo, H., Kida, M., Koji, I., & Usuki, K. (2009). Pancreatic atrophy is associated with gastrointestinal chronic GVHD following allogeneic PBSC transplantation. Bone Marrow Transplant.

• Nishio, N., Yagasaki, H., Takahashi, Y., Muramatsu, H., Hama, A., Tanaka, M., et al. (2009). Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transplant, 44(5), 303-308.

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• Nozzoli, C., Guidi, S., Paglierani, M., Wnekowicz, E., Saccardi, R., Bosi, A., et al. (2008). Immunohistochemical and FISH analyses identify synovitis associated with chronic GVHD after allogeneic hematopoietic SCT. Bone Marrow Transplant, 42(4), 289-291.

• Oda, K., Nakaseko, C., Ozawa, S., Nishimura, M., Saito, Y., Yoshiba, F., et al. (2009). Fasciitis and myositis: an analysis of muscle-related complications caused by chronic GVHD after allo-SCT. Bone Marrow Transplant, 43(2), 159-167.

• Ogawa, Y., Dogru, M., Uchino, M., Tatematsu, Y., Kamoi, M., Yamamoto, Y., et al. (2009). Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD. Bone Marrow Transplant.

• Oh, S. J., Cho, S. B., Park, S. H., Piao, C. Z., Kwon, S. M., Kim, I., et al. (2008). Cell cycle and immune-related processes are significantly altered in chronic GVHD. Bone Marrow Transplant, 41(12), 1047-1057.

• Palmer, J. M., Chen, B. J., Deoliveira, D., Le, N. D., & Chao, N. J. (2009). Novel mechanism of Rapamycin in GVHD: increase in interstitial regulatory T cells. Bone Marrow Transplant.

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• Pulanic, D., Lozier, J. N., & Pavletic, S. Z. (2009). Thrombocytopenia and hemostatic disorders in chronic graft versus host disease. Bone Marrow Transplant, 44(7), 393-403.

• Rackley, C., Schultz, K. R., Goldman, F. D., Chan, K. W., Serrano, A., Hulse, J. E., et al. (2005). Cardiac manifestations of graft-versus-host disease. Biol Blood Marrow Transplant, 11(10), 773-780.

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• Ruck, S., Hilgendorf, I., Muller-Hilke, B., Kiefel, V., Junghanss, C., Freund, M., et al. (2008). Autoantibody-mediated agranulocytosis in association with chronic GVHD. Bone Marrow Transplant, 42(5), 359-360.

• Sato, K., Eizumi, K., Fukaya, T., Fujita, S., Sato, Y., Takagi, H., et al. (2009). Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. Blood, 113(19), 4780-4789.

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• Shapira, M. Y., Abdul-Hai, A., Resnick, I. B., Bitan, M., Tsirigotis, P., Aker, M., et al. (2009). Alefacept treatment for refractory chronic extensive GVHD. Bone Marrow Transplant, 43(4), 339-343.

• Shelton, M. L., Lee, J. Q., Morris, G. S., Massey, P. R., Kendall, D. G., Munsell, M. F., et al. (2009). A randomized control trial of a supervised versus a self-directed exercise program for allogeneic stem cell transplant patients. Psychooncology, 18(4), 353-359.

• Skert, C., Damiani, D., Michelutti, A., Patriarca, F., Arpinati, M., Fili, C., et al. (2009). Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study. Bone Marrow Transplant, 44(11), 729-737.

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• Tam, P. M., Young, A. L., Cheng, L. L., & Lam, P. T. (2009). Topical 0.03% tacrolimus ointment in the management of ocular surface inflammation in chronic GVHD. Bone Marrow Transplant.

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• Thompson, B., Salzman, D., Steinhauer, J., Lazenby, A. J., & Wilcox, C. M. (2006). Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant, 38(5), 371-376.

• Tomblyn, M., Chiller, T., E.insele, H., Gress, R., Sepkowitz, K., Storek, J., Wingard, J., Young, J. and Boeckh, M. (2009). Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol Blood Marrow Transplant 15: 1143-1238.

• Veeraputhiran, M., & Mangan, K. (2009). Sudden loss of the GVL effect following use of the TNF inhibitor infliximab in a chronic myelogenous leukemia patient with chronic GVHD. Bone Marrow Transplant.

• Zaja, F., Bacigalupo, A., Patriarca, F., Stanzani, M., Van Lint, M. T., Fili, C., et al. (2007). Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant, 40(3), 273-277.

• Zhang, P. L., Wilkerson, M. L., & Schworer, C. M. (2008). C4d staining is a valuable marker in identifying chronic GVHD in colonic biopsies following BMT. Bone Marrow Transplant, 42(3), 209-211.

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