Optimizing the Treatment of Hematologic Malignancies With HSCT

Optimizing the Treatment of

Hematologic Malignancies With HSCT

Sergio A. Giralt, MD

Melvin Berlin Family Chair in Myeloma Research

Professor of Medicine

Weill Cornell Medical College

Chief Attending, Adult BMT Service

Memorial Sloan Kettering Cancer Center

Disclosures

Dr. Giralt discloses the following commercial

relationships:

Advisory Board: Amgen, Celgene, Jazz Pharmaceuticals, Kite

Pharma, Novartis, Sanofi, Takeda

Research Support: Amgen, Celgene, Janssen Pharmaceuticals,

Miltenyi Biotec, Sanofi, Takeda

Learning Objectives

Differentiate patient selection criteria for younger

versus older HSCT candidates

Apply emerging and evolving data on HSCT in

treatment planning for patients with hematologic

malignancies

Assess strategies to manage transplant-related

complications so that patients may achieve the

optimal HSCT outcomes

HSCT = hematopoietic stem cell transplant.

Indications for HSCT

PCD = primary ciliary dyskinesia; NHL = non-Hodgkin’s lymphoma; AML = acute myeloid

leukemia; HD = hemodialysis; ALL = acute lymphocytic leukemia; MDS = myelodysplastic

syndromes; MPN = myeloproliferative neoplasms; CLL = chronic lymphocytic leukemia; CML =

chronic myelogenous leukemia.

D'Souza & Zhu, 2016.

Annual Number of Auto vs Allo

Transplant Recipients


There Is a Significant Unmet Need for

HSCT Across All Indications

Besse et al, 2015.

Autologous Hematopoietic

Progenitor Cell Transplant

AHPCT = autologous hematopoietic progenitor cell transplant.

Costa et al, 2015.

# of Newly

Diagnosed Cases # of First AHPCTs

0

5000

10000

15000

20000

25000

18-49 50-64 65+

0

0.1

0.2

0.3

0.4

0.5

0.6

40 45 50 55 60 65 70 75 80 85 90

AHPCT “Utilization Rate”

0

5000

10000

15000

20000

25000

18-49 50-64 65+

Black man

Blackwomen

White man

Whitewomen

men

men

Barriers to HSCT Access

Majhail et al, 2010.

Access to Transplant

Donor Availability

Economic

Socioeconomic status

Education

Number of wage earners

Employment status

Insurance coverage

Place of residence

Transportation

Health Care System

Limited number of HSCT centers

Workforce shortage

Capacity limitations

Infrastructure issues

Provider

Physician referral

Provider attitudes/biases

Provider expertise

Provider diversity

Social

Age

Ethnicity and race

Language

Culture

Health literacy

Patient/family attitudes

Caregiver availability

HSCT Volume by Center

Based on 2010 total HSCT volume (N=84 centers)

Majhail, Mau et al, 2015.

Donor Availability No Longer the

Greatest Barrier to HSCT

Estey et al, 2007

2001-2003

99 AML/MDS patients in CR1

53 received HSCT consulto Donor identified in 49% of

patients

o 14 underwent allo HSCT in CR1

Most common stated reason for

not proceeding to HSCT:

o No donor

CR1 = first complete remission.

Estey et al, 2007; Mawad et al, 2013.

Mawad et al, 2013

2008-2011

116 AML patients in CR1

78 (67%) underwent HSCT

Reasons for not proceeding to

HSCT: o Early relapse (32%)

o Poor performance status

(21%)

o Financial or psychosocial

issues (21%)

Trends in Allogeneic HSCT by Agea

aTransplants for AML, ALL, NHL, Hodgkin lymphoma, and multiple myeloma.


100-Day Mortality by HCT-CI After Auto

HSCT: KPS and Malignancy

KPS = Karnofsky performance score; HCT-CI = Hematopoietic Cell Transplant Comorbidity Index.

Farina et al, 2009.

10

0-D

ay M

ort

alit

y (

%)

P<0.001 P<0.001P<0.001 P<0.001

0

5

10

15

KPS <80 KPS>80 Myeloma Lymphoma

HCT CI 0

HCT CI 1-2

HCT CI >3

KPS <80 KPS >80 Myeloma Lymphoma

2-Year Mortality Rate for

Patients Aged ≥70 Years

8% if fully independent

14% if dependent in IADL

27% if dependent in ADL

40% if institutionalized

IADL = instrumental activities of daily living; ADL = activities of daily living.

Reuben et al, 1992.

Geriatric Assessment Predicts

Survival and Toxicities

HR = hazard ratio; CI = confidence interval; CCI = Charlson Comorbidity Index; ISS = International Staging System; OS

= overall survival; PFS = progression-free survival; AEs = adverse events.

Palumbo et al, 2015.

OS and PFS by Risk Group

Palumbo et al, 2015.

Who Is Transplant Ineligible?

BiologicFrail and poor PS

Active uncontrolled

comorbidities

PsychosocialPoor caregiver support

Patient refusal

PS = performance status.

Majhail, Farnia et al, 2015.

Low-risk disease with

major responseRisk/benefit ratio

Progressive disease

Patients >85 years for

auto

Patients >80 years for

allo

Absolute Relative

HLA Matters and So Does Timing

Patients transplanted earlier in their disease have superior outcomes vs those with

advanced disease, regardless of the degree of match

HLA = human leukocyte antigen.

Lee et al, 2007.

8/8 Match 7/8 Match 6/8 Match

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

Surv

ival

Early Disease Stage Intermediate Disease Stage Advanced Disease Stage

Su

rviv

al

Su

rviv

al

Months After Transplant Months After Transplant Months After Transplant

Barriers to Referral

Late referral or lack of referralReferring physician’s unfamiliarity with the evolving indications

for HSCT

Financial disincentives

Different perspectives between oncologists and transplant

physicians regarding appropriate transplant candidates

Poor communication and coordination between referring

physician and transplant center

Costa et al, 2015.

HSCT Referral Guidelines

HSCT consultation timing for

15+ diseases

Recommended posttransplant

screening and preventive

practices

Clinical screening and diagnostic

tools for chronic GVHD

Recommended vaccination

schedule

GVHD = graft-versus-host disease.

Available via mobile app, print, and online

BeTheMatchClinical.org/guidelines

Case Study

67-year-old woman with history of NHL 5 years ago,

successfully treated with 6 cycles of CHOP-rituximab

Presents with progressive fatigue and is found to be

pancytopenic

Bone marrow aspiration reveals 28% myeloid blasts

with complex cytogenetic abnormalities

Diagnosed with AML

Has no HLA-compatible donors in the family. Two sons:

ages 30 and 32 years

Achieves a CR after induction therapy with cytarabine

and daunorubicin (“7+3” regimen)

NHL = non-Hodgkin lymphoma; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CR =

complete response.

Go or No Go?

Determinants of the Decision Process

Current

Expectation of cure with standard

chemo

Risk of death from transplant-

related complications

Risk of relapse post-HSCT

Future

Molecular classification that

separates standard risk groups

into subgroups with different risk

ratios

Novel treatment strategies that

may result in improved outcomes

(FLT3 inhibitors)

Improved donor selection

Better supportive care

Improved GVHD prophylaxis

Better conditioning regimens

Post-HSCT maintenance


Allo HSCT for High-Risk AML

Stelljes et al, 2011.

Transplant patients

Non-transplant patients

AML Revised Risk Stratification

Patel et al, 2012.

Favorable

Any

Favorable

Normal

karyotype or

intermediate-

risk

cytogenetic

lesions

Intermediate

Unfavorable

Unfavorable

FLT3-ITD-negative

FLT3-ITD-negative

FLT3-ITD-positive

FLT3-ITD-negative

FLT3-ITD-positive

FLT3-ITD-negative

or positive

Mutant NPM1 and IDH1 or IDH2

Wild-type ASXL1, MLL-PTD,

PHF6, and TET2

Mutant CEBPA

Wild-type MLL-PTD, TET2, and

DNMT3A and trisomy 8-negative

Mutant TET2, MLL-PTD, ASXL1,

or PHF6

Mutant TET2, MLL-PTD,

DNMT3A, or trisomy 8, without

mutant CEBPA

Any

Cytogenetic

Classification

Mutations Overall Risk

Profile

AML Revised Risk Stratification:

Integrated Genetic Analysis

Patel et al, 2012.

Prognostic Factors for Allo

HSCT-Related Nonrelapse Mortality

Cornelissen et al, 2012.

Pretransplant Peritransplant Posttransplant

Favorable prognostic factors

Sibling donor Nonmyeloablative conditioning

Shorter time from diagnosis to transplantStem-cell source (bone marrow

or peripheral blood)

White ethnicity

Adverse prognostic factors

Increased age Myeloablative conditioning Acute GVHD - Grade III-IV

Recipient and donor sex Alternative donorsChronic GVHD - Persistent,

extensive

Comorbidities

Cytomegalovirus status

Cytokine polymorphism

Unrelated donor

HLA-mismatched

Performance score

Refractory leukemia

Therapy-related AML

Recommendation for Allogeneic HSCT

for AML in CR1

NRM = nonrelapse mortality; WBC = white blood cell count.


Risk Assessment

Risk of Relapse

Prognostic Scores for NRM That

Would Indicate Allogeneic

HSCT as Preferred Consolidation

Chemotherapy or

Auto HSCT (%)

Allo

HSCT (%)

Prognostic

ScoreNRM (%)

Good

t(8;21) with WBC ≤20

inv(16)/t(16;16)

Mutated CEBPA (bi-allelic)

Mutated NPM1 (no FTL3-ITD

mutation)

Early first CR and no MRD

35-40 15-20 1 > 10-15

Intermediate

t(8;21) with WBC >20

Cytogenetically normal (or with

loss of X and Y chromosomes)

WBC ≤100 and early first CR

50-55 20-25 2≥ <20-25

Poor

No CR after first cycle of

chemotherapy

Cytogenetically normal and WBC

>100

Cytogenetically abnormal

70-80 30-40 ≥3-4 <30

Very poor Monosomal karyotype

Abn3q26

Enhanced Evi-1 expression

>90 40-50 ≥5 <40

Outcomes of Allo HSCT in

Elderly Patients With AML

RFS = relapse-free survival; CIR = cumulative incidence of relapse.

Rashidi et al, 2016.

CALGB 100103/BMT CTN 0502:

Outcomes by Donor Type

BMT CTN = The Blood and Marrow Transplant Clinical Trials Network.

Devine et al, 2015.

Nonrelapse Mortality by

Donor Type

Relapse by

Donor Type

HSCT in MDS: The Problem

Getta et al, 2016.

Components of the HSCT

PatientIndication

Comorbidity

Cell sourceAutologous vs allogeneic

Related vs unrelated

Bone marrow vs peripheral blood vs cord blood

Manipulated vs unmanipulated

Conditioning regimenChemical and physical agents to eliminate malignant disorder

and “open space” for donor cells

Components of the HSCT (cont.)

Supportive careProtocols and SOPs required to maintain organ function and

prevent serious fatal complications in severely immune-

compromised patients recovering from the effects of high-dose

therapy○ Hydration and electrolytes

○ Antibiotics

○ Graft-versus-host disease prevention

○ Nutrition

○ Symptom management

Post-HSCT therapies Prevent relapse

Monitor and treat long-term complications

SOPs = standard operating procedures.

Allo-HSCT Recipients in US

by Donor Type

URD = unrelated donor; BM = bone marrow; PB = peripheral blood; UCB = umbilical cord blood.


Relative Risks and Benefits of Different

Cell Sources


Unrelated Donor Cord Haplo

Engraftment Fast Slow Fast

Graft failure Rare More commonRare with new

techniques

GVHDHigh (esp with

mismatch)

Lower than

expected with

mismatch

Low due to

techniques

RelapsePossibly lower than

sibling

Possibly lower

than siblingHigher

Overall survival Many recent studies show equivalence

Haploidentical vs Unrelated Donor:

Overall Survival

Ciurea et al, 2015.

Haploidentical vs Unrelated Donor:

Nonrelapse Mortality

Ciurea et al, 2015.

Minnesota-Fred Hutchinson

Experience: Leukemia-Free Survival

MM URD = mismatched unrelated donor; DUCB = double umbilical cord blood.

Brunstein et al, 2010.

Cu

mu

lative

Pro

po

rtio

n

MRD

P = 0.19

MM URD

MUDDUCB

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5

II I I II I I I IIIIIIIIIII

II

IIIII

I II II I

I I I I I II I I I I I I I II I I I III II I I I I IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII

III

II IIIIIIIII I

II I II IIIIIIIIIIIIIII IIIII II I I I I I I I I I I I I I IIII I I IIIIII

III

I

IIIIIIIIII II I I II I IIIII II I III III I I

IIII IIII II I I II II I III IIII I II I IIIIIIIIIIIIII

Years Posttransplant

Minnesota-Fred Hutchinson

Experience: Relapse by Donor Type

Brunstein et al, 2010.

Cu

mu

lative

In

cid

en

ce

MRD

P < 0.01

MMUD

MUD

DUCB0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5Years Posttransplant

Donor Selection: Current Status

With the increasing availability of alternative donors,

donor availability should no longer be the most common

barrier to HSCT

In 2017, the algorithm remains the same:1st choice: 10/10 sibling donor

2nd choice: 10/10 unrelated donor

3rd choice: Alternative donor of preference

This algorithm is much more flexible and should

considerNeed for rapid HSCT

Donor age and comorbidities

Donor-specific antibodies

Other HLA disparities

Autologous Stem Cell Sources by

Recipient Age

Pasquini & Wang, 2013.

Disease-Free Survival From Transplant

Anasetti et al, 2012.

Cumulative Incidence of Chronic GVHD

From Time of Transplant

Anasetti et al, 2012.

Treatment Arm

Bone Marrow Peripheral Blood

N (%) N (%)

None 160 (60.6%) 128 (48.9%)

Limited 23 (8.7%) 13 (5.0%)

Extensive 81 (30.7%) 121 (46.2%)

Total 264 (100.0%) 262 (100.0%)

TRM and LFS in Patients With Acute and Chronic

Leukemia After BM and PBSC Transplant

TRM = transplant-related mortality; LFS = leukemia-free survival; PBSC = peripheral blood stem cell.

Schmitz et al, 2006.

Conditioning Regimen Effects

Gyurkocza & Sandmaier, 2014.

Conditioning Regimen Spectrum

High

Intensity

Low

Intensity

Increase immediate antitumor effect

Increase toxicity

Rely on later graft-versus-disease effect

Decreased regimen-related toxicity

Number of

candidates for

HSCT

Common Conditioning Regimens in

AML or MDS Allo HSCT: 2000-2015

MAC = myeloablative conditioning; RIC = reduced-intensity conditioning; TBI = total body irradiation.


Nonrelapse Mortality in AML:

Myeloablative Conditioning

EBMT = European Group for Blood and Marrow Transplantation.


100

80

60

40

20

1 2 3 4 5

No

nre

lap

se

Mo

rtality

(%)

0

Years

EBMT Data

0 (n=598): 5% (4–8%)

1 (n=2,378): 12% (10–13%)

2 (n=3,482): 19% (18–21%)

3 (n=1,900): 27% (24–29%)

4–5 (n=300): 34% (28–40%)EBMT Factors:

Age >50

Disease not in CR1

Donor not 10/10 sib

Time to transplant >1 yr

Female donor/male patient

Nonrelapse Mortality in AML: Reduced-

Intensity Conditioning


100

80

60

40

20

1 2 3 4 5

No

nre

lap

se

Mo

rtality

(%)

0

Years

EBMT Risk Score

1 (n=164): 12% (7–19%)

2 (n=1,413): 14% (12–16%)

3 (n=1,410): 24% (21–26%)

4–5 (n=239): 25% (19–32%)

Causes of HSCT Morbidity and Mortality

EBV = Epstein-Barr virus; PTLD = posttransplant lymphoproliferative disorder.

ACS, 2016.

→ Mucositis

→ Infection due to neutropenia

→ Hemorrhagic cystitis

→ Cardiomyopathy

→ Sinusoidal obstruction disease

→ Graft rejection

→ Graft-versus-host disease

→ Opportunistic infection

→ EBV - PTLD

→ Disease recurrence

→ Endocrine: growth, infertility, cataracts, caries

→ Secondary malignancies

Early Late

Risk Factors for Regimen Toxicity

Patient relatedComorbiditiesPrior therapyDisease statePolymorphismsSocioeconomic status

Regimen relatedIntensityAgents used○ Gemtuzumab

ozogamicin○ Inotuzumab○ Radiation○ Busulfan○ Myeloablative

MTX = methotrexate.

Bacigalupo et al, 2009.

Transplant relatedStem cell source○ Auto

○ Allo

○ Cord

○ Matched/mismatched

GVHD prophylaxis○ MTX

○ Posttransplant

cyclophosphamide

○ CD34 selection

Prognostic Tools for HSCT

Several prognostic risk scores predict mortality risk

after HSCTHCT-CI

EBMT risk assessment score for allogeneic HSCT

Pretransplant Assessment of Mortality (PAM) score

CIBMTR 1-year survival calculator

As patient selection, conditioning regimens, and

supportive care strategies evolve, these scores will

need to be revalidated

CIBMTR = Center for International Blood and Marrow Transplant Research.

Sorror et al, 2005; Gratwohl et al, 1998; Parimon et al, 2006.

Impact of Charlson Comorbidities

Sorror et al, 2005.

Nonrelapse Mortality and

Overall Survival by HCT-CI

Sorror et al, 2005.

BMT CTN 0901:

Randomized Phase III Design

Scott et al, 2017.

MDS/AML

BM <5% Blasts

Randomization

RIC Regimens:

Flu/Bu

Flu/Mel

MAC Regimens:

Bu/Flu

Bu/Cy

Cy/TBI

18-Month Overall Survival

GVHD Prophylaxis

T-cell Replete per

Institutional

Guidelines

MAC vs RIC Regimen Choices

Regimen was prespecified by center before randomization

Scott et al, 2017.

Prespecified Regimen Pair Patients n (%)

MAC RIC Total

Flu/Bu4 vs Flu/Bu2 79 (58.5) 78 (56.9) 157 (57.7)

Flu/Bu4 vs Flu/Mel 8 (5.9) 10 (7.3) 18 (6.6)

Bu4/Cy vs Flu/Bu2 20 (14.8) 22 (16.1) 42 (15.4)

Bu4/Cy vs Flu/Mel 20 (14.8) 16 (11.7) 36 (13.2)

Cy/TBI vs Flu/Bu2 7 (5.2) 10 (7.3) 17 (6.3)

Cy/TBI vs Flu/Mel 1 (0.7) 1 (0.7) 2 (0.7)

Total 135 137 272

Overall Survival by Disease Group

Scott et al, 2017.

Relapse-Free Survival by

Treatment Arm

Scott et al, 2017.

P<0.01 (18 mo pointwise)

Difference of MAC and RIC, 20.4%

(95% CI: 8.8%, 31.9%)

Relapse/Progression by

Disease and Treatment Arm

Scott et al, 2017.

Treatment-Related Mortality

Scott et al, 2017.

P = 0.002

Selecting the Conditioning Regimen

No longer does “one size fit all”Patient and disease characteristics should guide choice of

conditioning regimen

For autografts, intensity is important but

melphalan 140 vs 200 mg/m2 preferred for older patients

In myeloid leukemias, dose intensity may be

important but TBI may not be beneficial

PK-directed busulfan should be standard of carePotential role for PK-directed therapy for other agents

PK = pharmacokinetic.


Case Study (cont):

Planning the Transplant

Because of patient’s age and disease status she

receives fludarabine/busulfan for 3 days with PK

monitoring

Her donor is a young 30-year-old man who is

matched at 10/10 alleles

You discuss various GVHD prophylactic strategies

and because of a history of recurrent CMV infection

during her induction therapy you opt for the

standard tacrolimus and methotrexate with donor

bone marrow support

CMV = cytomegalovirus.

5 Phases of Transplant

HSV = herpes simplex virus; IP = interstitial pneumonitis; PCP = pneumocystis; QoL = quality of life; VOD = veno-occlusive disease;

VZV = varicella zoster virus.

Bredeson, 2006.

Transplant Complications

TPN = total parenteral nutrition.

Apperley et al, 2012.

Complication Comment

Marrow toxicity

Common complication

Management

o Neutropenia: Growth factor support

o Anemia and thrombocytopenia: Transfusional support

Mucositis

Common complication

Incidence and severity associated with regimen intensity and patient

characteristics

Pain and compromised nutritional intake common

Management: Palifermin, oral care, pain control, TPN

Diffuse alveolar

hemorrhage

Rare complication (incidence <1%) but with high mortality (>80%)

Associated with infection, diffuse alveolar damage

Clinical presentation: Dyspnea, tachypnea, and hypoxia;

hemoptysis rare

Management: High-dose steroids + transfusion support

Transplant Complications (cont.)

TLS = tumor lysis syndrome.

Apperley et al, 2012; Dalle & Giralt, 2016.

Complication Comment

Cardiac toxicity

Preexisting conditions (eg, coronary artery disease, prior regimen-

related toxicity, disease-related amyloidosis)

Cardiomyopathy

Arrhythmias

Hypertension

Acute renal toxicity

Most common causes: acute tubular necrosis, calcineurin inhibitors,

amphotericin B, aminoglycosides, sinusoidal obstruction syndrome

Less common cause: TLS, thrombotic microangiopathy, emolysis due

to ABO incompatibility

Often multifactorial

Sinusoidal

obstruction syndrome

(veno-occlusive

disease)

Risk factors: preexisting liver conditions (eg, hepatitis, cirrhosis) prior

therapy (eg, second transplant), conditioning regimen (eg, busulfan,

high-dose radiation)

Diagnosis based on clinical suspicion, ultrasound (ascites, abnormal

portal vein waveform, reversal of flow in the portal vein, increased

hepatic artery resistance index), and liver biopsy

Defibrotide for SOS:

Survival Up to Day +100

SOS = sinusoidal obstruction syndrome.

Richardson et al, 2016.

Su

rviv

al

(%)

No. at risk:

Defibrotide 102 101 93 86 71 65 55 50 46 42 39

Controls 32 32 27 23 17 12 11 10 9 9 8

Time Since Transplant (d)

Defibrotide (n=102)

Controls (n=32)

P = 0.0499

Graft-Versus-Host Disease

AcuteMaculopapular rash, persistent nausea/vomiting, abdominal cramps with diarrhea, rising bilirubin○ Within <100 days: Classic acute GVHD○ After 100 days: Late acute GVHD

Incidence○ Up to 40% of sibling donor recipients○ Up to 70% of unrelated donor recipients

Prophylaxis○ Cyclosporine/methotrexate

Treatment○ Grade 1: Topical steroid○ Grade ≥2: Corticosteroid○ Steroid-refractory: ATG, monoclonal antibodies, MSC, ECP, ruxolitinib

Supportive care○ Antimicrobial prophylaxis, antibody replacement, manage

hyperglycemia and cytopenia

ATG = antithrombocyte globulin; MSC = mesenchymal stromal cells; ECP = extracorporeal photochemotherapy.

Socié & Ritz, 2014.

Graft-Versus-Host Disease (cont.)

ChronicSkin involvement resembling lichen planus or scleroderma, dry

oral mucosa with ulcerations, sclerosis of GI tract, rising

bilirubin○ With signs of acute GVHD: Overlap syndrome

Occurs in 40-70% of allo HSCT patients

Prophylaxis○ ATG

○ Other preventive agents for acute GVHD have no effect on chronic

GVHD

Treatment○ Corticosteroid

○ Ibrutinib (approved 2017) after corticosteroid failure

GI = gastrointestinal.

Socié & Ritz, 2014; Palmer et al, 2012; Miklos et al, 2017.

Opportunistic Infection

HHV = human herpesvirus.

Tomblyn et al, 2009.

Patients must be carefully

monitored and receive early

intervention for signs or symptoms

of infection

Immunocompetence improves

progressively with increasing time

after transplant in most patients

Many remain

immunocompromised >2 years

posttransplant, especially those

with chronic GVHD

Causes of Death After HLA-Matched

Sibling HSCT: 2013-2014


Causes of Death After Unrelated Donor

HSCT: 2013-2014


Key Takeaways

Donor availability is no longer the most common barrier

to HSCT

Patient and disease characteristics should guide choice

of conditioning regimen

Patients transplanted earlier in their disease have better

outcomes than patients with advanced disease,

regardless of the degree of match

As patient selection, conditioning regimens, and

supportive care strategies evolve, prognostic tools will

need to be revalidated

Questions?

References

American Cancer Society (2016). Stem cell transplant side effects. Available at: https://www.cancer.org

Anasetti C, Logan BR, Lee SJ, et al (2012). Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med,

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Apperley J, Carreras E, Gluckman E & Masszi T, Eds. (2012). The 2012 revised edition of the EBMT-ESH Handbook on Haematopoietic Stem

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Bacigalupo A, Ballen K, Rizzo D, et al (2009). Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant,

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Ciurea S, Zhang MJ, Bacigalupo AA, et al (2015). Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor

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Cornelissen JJ, Gratwohl A, Schlenk RF, et al (2012). The European LeukemiaNet AML Working Party consensus statement on allogeneic

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DOI:10.1038/nrclinonc.2012.150

Costa LJ, Kumar S, Stowell SA, et al (2015). Mobilization and transplantation patterns of autologous hematopoietic stem cells in multiple

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D'Souza A & Zhu X (2016). Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR summary slides. Available

at: http://www.cibmtr.org

Dalle JH & Giralt SA (2016). Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification,

prophylaxis, and treatment. Biol Blood Marrow Transplant, 22(3):400-409. DOI:10.1016/j.bbmt.2015.09.024

References

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