Indications for High-Dose Cytotoxic
Therapy with Stem Cell Transplantation
Evidence-Based Reviews
ASBMT Evidence-Based Reviews
“The practice of evidence-based
medicine means integrating individual
clinical expertise with the best available
external clinical evidence from
systematic research.”
Sackett, D.L. et al. Evidence-based
medicine: what it is and what it isn't. BMJ
1996;312:71-72.
ASBMT Evidence-Based Reviews
Goals
Define accepted medical practice
Promote evidence-based decisions
Improve treatment outcomes
Determine areas of needed research
ASBMT Evidence-Based Reviews
Steps
 Assemble evidence for selected diseases
 Evaluate strength and quality of the evidence
 Identify discrepancies in study design or
methodology
 Make treatment recommendations
 Recommend areas of needed research
 Advocate best treatment for all patients
 Improve access/reimbursement
 Inform patients, providers, and payers
ASBMT Evidence-Based Reviews
Benefits of Evidence-Based Medicine
Improved Patient Care
 Aid treatment decisions of referral physicians and their
patients
 Assist in reimbursement policies and decisions
 Enhance technology assessment
 Identify areas of needed research
 Foster quality of study design/methodology
 Document best practices/standards of care
ASBMT Evidence-Based Reviews
The Review Process
ASBMT Steering Committee
 Establishes criteria for grading evidence and
inclusion/exclusion criteria for evidence
 Maintains standards of evidence-based
medicine
 Identifies diseases for review
 Nominates expert panelists for each review
ASBMT Evidence-Based Reviews
The Review Process
Expert Panel for Each Disease
 Transplant specialists
 Disease-specific experts for non-transplant
therapies
 Third-party payer
 Patient advocate
ASBMT Evidence-Based Reviews
The Review Process
Expert Panel for Each Disease
 Identifies areas of inquiry/parameters of review
 Guides and advises literature search, writing
 Evaluates strength/quality of evidence
 Reaches consensus on treatment
recommendations
 Recommends areas for further study
ASBMT Evidence-Based Reviews
Completed Evidence-Based Reviews
• Acute Lymphoblastic Leukemia in Children
(2005, updated 2012)
• Acute Lymphoblastic Leukemia in Adults (2006,
updated 2012)
• Diffuse Large B-Cell Non-Hodgkin Lymphoma
(2001, updated 2011)
• Follicular Lymphoma (2010)
• Myelodysplastic Syndromes (2009)
• Acute Myeloid Leukemia in Adults (2008)
• Acute Myeloid Leukemia in Children (2007)
• Multiple Myeloma (2003)
ASBMT Evidence-Based Reviews
Future Directions
• Periodic updating of completed reviews based on
evolving standards and new scientific evidence.
• Acute Myeloid Leukemia in adults - update
in 2012
• Acute Myeloid Leukemia in children update in 2012
ASBMT Evidence-Based Reviews
EBR Update Process
• Updates occur in the same order as the publication of original
EBRs, unless there is a substantial reason to change the order of
a specific review
• The original expert panel is invited to participate in the update
• New evidence is presented in summary tables along with high
level evidence from the original EBR
• Updated Treatment Recommendations indicate whether new
evidence strengthens, weakens, or does not change the
original recommendations
ASBMT Policy Statement on updating published EBRs:
Biology of Blood and Marrow Transplantation
(Vol. 15:761-762) June 2009
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell Transplantation
in the Therapy of Pediatric Acute
Lymphoblastic Leukemia (ALL): Update of
the 2005 Evidence-Based Review”
Biology of Blood and Marrow Transplantation
2012, in press.
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT is recommended for pediatric
ALL patients who experience primary induction
failure, but subsequently achieve a first
complete remission (CR1); new evidence has
changed the original recommendation
• Allogeneic SCT is recommended for pediatric
patients with precursor-B ALL in CR2 after an
early marrow relapse; new evidence has
changed the original recommendation
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT is recommended for pediatric Tlienage ALL patients in CR2 after a marrow
relapse; this is a new recommendation based
on evidence in the original review and expert
opinion
• Allogeneic SCT is recommended for pediatric
patients with ALL in CR3 or greater; this is a new
recommendation based on new evidence
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT may be considered for some
patients with T-lineage ALL in CR1; this is a new
recommendation based on new limited
evidence and expert opinion.
• Allogeneic SCT may be considered for children
with hypodiploid ALL (<44 chromosomes) in CR1;
this is a new recommendation based on expert
opinion
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT may be considered for patients
with ALL in CR1 or CR2 who have minimal
residual disease detected by a validated assay;
this is a new recommendation based on expert
opinion
• Allogeneic SCT may be considered for patients
with ALL who are not in morphologic CR; this is a
new recommendation based on expert opinion
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT and chemotherapy provide
equivalent outcomes for pediatric precursor-B
ALL patients in CR2 after experiencing a later
marrow relapse; new data have changed the
original recommendation
• Allogeneic SCT and intensive chemotherapy
with imatinib have equivalent early outcomes
for Ph+ ALL in CR1; new evidence changed the
original recommendation. Further study is
needed in this area
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT is not recommended for an
isolated CNS relapse in precursor-B pediatric ALL
patients; this is a new recommendation based
on new evidence
• Autologous SCT is not recommended in CR1; this
is a new recommendation based on new
evidence
ASBMT Evidence-Based Reviews
ALL in Children
RECOMMENDATIONS
• Allogeneic SCT is not recommended when MLL+
ALL is the sole adverse risk factor; this is a new
recommendation based on new evidence. The
presence of MLL+ along with other adverse risk
factors (older age, high WBC, prednisone
response, other cytogenetic abnormalities) has
been used to define very high risk subgroups for
which allogeneic SCT may be recommended
ASBMT Evidence-Based Reviews
ALL in Children
ALLOGENEIC SCT TECHNIQUES
• Myeloablative Total Body Irradiation (TBI)
containing conditioning regimens are
recommended; new data have strengthened
the original recommendation
• HLA-matched related and unrelated donors
provide equivalent outcomes. In the absence of
an HLA-matched related donor, an HLAmatched unrelated donor (using marrow,
peripheral blood or cord blood ) is acceptable
for allogeneic SCT; this is a new
recommendation based on new evidence
ASBMT Evidence-Based Reviews
ALL in Children
ALLOGENEIC SCT TECHNIQUES
• Allogeneic SCT using the best possible HLAmatched unrelated donor is recommended.
HLA-mismatched unrelated donor allogeneic
SCT may result in higher morbidity and mortality
than an HLA-matched unrelated donor, but this
does not preclude use of HLA-mismatched
unrelated donors; this is a new recommendation
based on new evidence
ASBMT Evidence-Based Reviews
ALL in Children
INCONCLUSIVE EVIDENCE
There is insufficient evidence to support a
recommendation regarding:
• Allogeneic SCT for treatment of an isolated CNS
relapse in pediatric patients with T-lineage ALL
• Allogeneic SCT for treatment of an isolated
testicular relapse in pediatric ALL patients
• Use of a maternal vs a paternal donor for
allogeneic SCT in pediatric ALL patients
• Use of imatinib therapy along with allogeneic
SCT in pediatric Ph+ ALL patients
ASBMT Evidence-Based Reviews
ALL in Children
AREAS OF NEEDED RESEARCH
• Re-evaluate allogeneic SCT versus intensive
chemotherapy regimens in the current era, as
both approaches have changed
• Investigate the role and potential benefit of
maternal antigen microchimerism to reduce the
risk of graft-versus-host disease and enhance the
graft- versus-leukemia effect after allogeneic
BMT
• Identify and address the treatment of high risk Tlineage ALL subsets
ASBMT Evidence-Based Reviews
ALL in Children
AREAS OF NEEDED RESEARCH
• Re-evaluate the promising early studies of
imatinib in combination with chemotherapy or
SCT for Ph+ ALL in larger studies
• Investigate the optimal treatment for patients
who are persistently positive for minimal residual
disease
• Improve the detection and monitoring of MRD
during initial treatment to guide individual
patient eligibility and timing of allogeneic SCT
• Monitoring MRD after SCT to detect early postSCT relapse in need of pre-emptive therapy
ASBMT Evidence-Based Reviews
ALL in Children
AREAS OF NEEDED RESEARCH
• Investigate the indications for using reduced
intensity versus myeloablative conditioning
regimens for allogeneic SCT
• Determine conditioning regimens which reduce
or eliminate the need for TBI while maintaining
effectiveness for ALL
• Investigate the prognostic role of initial risk
classification (NCI SR/HR assignment) on
outcomes after relapse
ASBMT Evidence-Based Reviews
ALL in Children
AREAS OF NEEDED RESEARCH
• Investigate whether allogeneic SCT performed in
CR1 patients identified as very high risk for
relapse by molecular methods (i.e., specific
gene mutations, gene expression profiles, etc.)
improves outcome compared to chemotherapy
• Investigate the impact of psychosocial support
and shared decision-making models to assist
families in weighing the risks versus benefits of
SCT for their children with ALL
ASBMT Evidence-Based Reviews
ALL in Children
THE EXPERT PANEL MEMBERS
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Denise Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY
Bruce Camitta, Midwest Center for Cancer and Blood Disorders, Medical
College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, WI
Paul Gaynon, Children’s Hospital of Los Angeles, Los Angeles, CA
Michael L. Nieder, All Children’s Hospital, St Petersburg, FL
Susan K Parsons, Tufts Medical Center, Boston, MA
Michael A Pulsipher, University of Utah, Huntsman Cancer Institute, Salt
Lake City, UT
Hildy Dillon, The Leukemia and Lymphoma Society, White Plains, NY
Thomas A Ratko, Blue Cross and Blue Shield Technology Evaluation
Center, Chicago, IL
Donna Wall, University of Manitoba, Cancer-Care Manitoba, Winnipeg,
Manitoba, Canada
Philip L. McCarthy, Jr., RPCI, Buffalo, NY
Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell Transplantation
in the Treatment of Adult Acute
Lymphoblastic Leukemia: Update of the
2006 Evidence-Based Review”
Biology of Blood and Marrow Transplantation
(Vol. 18:18-36) 2012
ASBMT Evidence-Based Reviews
ALL in Adults
RECOMMENDATIONS
• Myeloablative allogeneic SCT is recommended
for adult ALL in CR1 for all disease risk subgroups;
this is a new recommendation based on new
evidence
• Allogeneic SCT is recommended for adult ALL in
CR2; new evidence strengthens the original
recommendation
• Imatinib therapy before and/or after allogeneic
SCT is recommended for adult Ph+ ALL; this is a
new recommendation based on new evidence
ASBMT Evidence-Based Reviews
ALL in Adults
SCT TECHNIQUES
• Allogeneic SCT is recommended over
autologous SCT for adult ALL; new evidence
strengthens the original recommendation
• In the absence of a suitable allogeneic SCT
donor, autologous SCT may be considered for
adult ALL in CR1; this is a new recommendation
based on new evidence
ASBMT Evidence-Based Reviews
ALL in Adults
ALLOGENEIC SCT TECHNIQUES
• HLA-matched related and unrelated donor
allogeneic SCT produces equivalent survival
outcomes, but post-SCT complications may
differ; new evidence strengthens the original
recommendation
• In the absence of an HLA-matched donor, a
cord blood transplant may be considered; this is
a new recommendation based on new
evidence
ASBMT Evidence-Based Reviews
ALL in Adults
ALLOGENEIC SCT TECHNIQUES
• Myeloablative TBI-containing regimens in
preparation of allogeneic SCT are
recommended; new evidence strengthens the
original recommendation
• Reduced intensity conditioning regimens
produce similar outcomes to myeloablative
regimens, but are recommended only for
patients with adult ALL in remission who are
unsuited for myeloablative conditioning
regimens
ASBMT Evidence-Based Reviews
ALL in Adults
INCONCLUSIVE EVIDENCE
There is insufficient evidence to make a
recommendation regarding:
• The superiority of one conditioning regimen over
another
• The benefit of any one induction regimen
before allogeneic SCT
ASBMT Evidence-Based Reviews
ALL in Adults
AREAS OF NEEDED RESEARCH
• Re-evaluate allogeneic SCT versus more
intensive chemotherapy regimens, especially in
younger (<35 yrs) adults, and in the context of
biologic therapies and TKIs (for Ph+ ALL)
• Assess the ability of TKIs to reduce the leukemia
burden pre- or post-SCT in Ph+ ALL patients and
evaluate whether this can improve survival
outcomes after autologous and allogeneic SCT.
Studies of different TKIs, dose and schedule will
be important
ASBMT Evidence-Based Reviews
ALL in Adults
AREAS OF NEEDED RESEARCH
• Improvement in the detection and monitoring of
minimal residual disease (MRD) during initial
treatment to guide individual patient eligibility
and timing of allogeneic SCT
• Monitoring of MRD after SCT to detect early
post-SCT relapse in need of pre-emptive
therapy. This may indicate patients at higher risk
of early recurrence, but effective therapy will
also need to be developed
• Indications for using reduced intensity versus
myeloablative conditioning regimens for
allogeneic SCT
ASBMT Evidence-Based Reviews
ALL in Adults
AREAS OF NEEDED RESEARCH
• Evaluation of cord blood transplantation
techniques, such as single unit, double unit, and
ex vivo expansion, to improve survival outcomes
and reduce TRM
• Assessment of patient quality of life and
functional status after successful SCT
• Assess the impact of management plans and
follow-up care to facilitate better quality of life
for ALL patients, regardless of treatment
ASBMT Evidence-Based Reviews
ALL in Adults
THE EXPERT PANEL MEMBERS
• Denise M. Oliansky, Roswell Park Cancer Institute (RPCI),
Buffalo, NY
• Richard A. Larson, University of Chicago, Chicago, IL
• Daniel Weisdorf, University of Minnesota, Minneapolis, MN
• Hildy Dillon, The Leukemia & Lymphoma Society, White
Plains, NY
• Thomas A. Ratko, Blue Cross Blue Shield Association
Technology Evaluation Center, Chicago, IL
• Donna Wall, University of Manitoba/CancerCare
Manitoba, Winnipeg, Manitoba, Canada
• Philip L. McCarthy Jr., RPCI, Buffalo NY
• Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell
Transplantation in the Treatment
of Diffuse Large B Cell Lymphoma:
Update of the 2001 EvidenceBased Review”
Biology of Blood and Marrow Transplantation
2011, 17:20-47.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
RECOMMENDATIONS
AUTOLOGOUS SCT VS. NON-TRANSPLANT THERAPY
• Autologous SCT provides a significant survival benefit and
is recommended as part of salvage therapy for patients
with chemosensitive relapsed DLBCL. This original
recommendation is unchanged with no new data
published since the original EBR.
• Autologous SCT is not recommended for patients who
achieve only a partial response to an abbreviated (3
cycles) induction regimen. This original recommendation is
unchanged with no new data published since the original
EBR.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AUTOLOGOUS SCT VS. NON-TRANSPLANT THERAPY
• Autologous SCT provides a significant survival benefit and is
recommended as part of salvage therapy for patients with
chemosensitive relapsed DLBCL. This original
recommendation is unchanged with no new data
published since the original EBR.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AUTOLOGOUS SCT TIMING AND PROTOCOL
•
Based on new data published since the original EBR, older
age (> 60 years is not a contraindication for autologous
SCT as long as other SCT eligibility criteria are met.
However, SCT outcomes (transplant-related mortality,
relapse, survival) in older adults are not as good as in
younger adults.
•
Based on new data published since the original EBR,
autologous SCT using peripheral blood, compared to bone
marrow, provides no survival benefit or improved tumor
control. However, autologous SCT using peripheral blood is
safer and easier to use with faster engraftment and lower
rate of death due to infection, hence peripheral blood is
the standard autologous stem cell source.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AUTOLOGOUS SCT TIMING AND PROTOCOL
• Based on new data published since the original EBR,
planned tandem or multiple sequential autologous SCTs
are not recommended.
• The new data published since the original EBR are
insufficient to recommend routine post-autologous SCT
maintenance with rituximab outside of a clinical trial.
• The new data published since the original EBR are
insufficient to make a treatment recommendation
regarding fewer versus more cycles of induction therapy
prior to first-line autologous SCT.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AUTOLOGOUS VERSUS ALLOGENEIC SCT
• Based on new data published since the original EBR, there
are equivalent survival outcomes after autologous and
allogeneic SCT. Neither donor option is recommended
over the other since they have competing risks with
regard to relapse and transplant-related mortality.
Comparison of these two techniques is biased by different
patient selection criteria.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
ALLOGENEIC SCT CONDITIONING
• The new data published since the original EBR are
insufficient to recommend reduced intensity versus
myeloablative conditioning for allogeneic SCT. Based on
one study and expert opinion, reduced intensity
conditioning appears to be an acceptable alternative
approach for selected patients who cannot tolerate a
myeloablative allogeneic SCT. Longer follow-up is needed
to clarify the competing risks of relapse and chronic
GVHD and their impact on overall survival and quality-oflife. Comparison of these regimen intensities is biased by
patient selection criteria which have changed over time.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AREAS OF NEEDED RESEARCH
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Identify more effective induction regimens to optimize disease
response and reduce the need for autologous SCT.
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Identify and examine the efficacy of predictive tests (i.e.,
Positron Emission Tomography scans) to classify patients who are
at high risk for early treatment failure (those who are primary
refractory to initial therapies and those who respond but quickly
relapse) and candidates for autologous SCT.
•
Update the International Prognostic Index to include molecular
markers and/or gene expression profiling to better discriminate
prognostic groups that would benefit from SCT.
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Determine the potential benefit of first-line autologous SCT for
patients with central nervous system involvement.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
AREAS OF NEEDED RESEARCH
• Identify effective salvage regimens to optimize disease
response prior to autologous SCT.
• Identify effective high dose therapy regimens to optimize
complete response, improve hematopoietic recovery,
and reduce transplant-related mortality and incidence of
secondary malignancies.
• Identify effective maintenance regimens to optimize
disease control post-autologous SCT.
• Examine the efficacy of reduced intensity allogeneic SCT
as rescue after a failed autologous SCT.
ASBMT Evidence-Based Reviews
Diffuse Large B Cell Lymphoma
THE EXPERT PANEL
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Denise M. Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY
Myron Czuczman, RPCI, Buffalo, NY
Richard I. Fisher, University of Rochester, James P. Wilmot Cancer Center,
Rochester, NY
Frank D. Irwin, Optum Health Care Solutions, Minneapolis, MN
Hillard M. Lazarus, Case Comprehensive Cancer Center, University
Hospitals Case Medical Center, Case Western Reserve University,
Cleveland, OH
James Omel, Independent Patient Advocate, Grand Island, NE
Julie Vose, University of Nebraska Medical Center, Omaha, NE
Steven N. Wolff, Meharry Medical College and Vanderbilt University,
Nashville, TN
Roy B. Jones, MD Anderson Cancer Center, Houston, TX
Philip L. McCarthy Jr., RPCI, Buffalo NY
Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy
with Hematopoietic Stem Cell
Transplantation in the Therapy of
Follicular Lymphoma:
An Evidence-Based Review”
Biology of Blood and Marrow Transplantation
(Vol. 16:443-468) April 2010
ASBMT Evidence-Based Reviews
Follicular Lymphoma
RECOMMENDATIONS
AUTOLOGOUS SCT VS. NON-TRANSPLANT THERAPY
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Based on pre-rituximab data, there is a statistically
significant improvement in overall survival (OS) and
progression-free survival (PFS) using autologous stem cell
transplantation (SCT) as salvage therapy.
With only one retrospective study, there are insufficient
data to make a recommendation on the use of
autologous SCT versus non-transplantation therapy as
salvage treatment for patients who have had rituximab as
part of their salvage therapy.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AUTOLOGOUS SCT VS. NON-TRANSPLANT THERAPY
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Autologous SCT is recommended for transformed follicular
lymphoma patients, based on expert opinion and
accepted clinical practice.
Although there is consistent improvement in PFS and
event-free survival (EFS) with autologous SCT, it is not
recommended as first-line treatment for most patients
because of no significant improvement in OS, a higher
incidence of secondary myelodysplastic syndrome (MDS)
and acute myeloid leukemia (AML), and a lack of
comparative data with rituximab-containing regimens.
Longer follow-up may be needed to identify differences
in OS.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AUTOLOGOUS SCT TIMING AND PROTOCOL
 There are insufficient data to make a
recommendation on the efficacy of autologous
SCT as first-line versus salvage therapy.
 Due to conflicting data, a recommendation
cannot be made on the use of rituximab as part
of first-line or salvage regimens prior to
autologous SCT.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AUTOLOGOUS SCT TIMING AND PROTOCOL
 There are insufficient data to make a
recommendation regarding purging in
autologous SCT.
 There are insufficient data to recommend one
high dose regimen over another. Total body
irradiation (TBI)-containing regimens are usually
avoided because of a concern for the risk of
secondary MDS or AML.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AUTOLOGOUS VERSUS ALLOGENEIC SCT
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There are insufficient data comparing autologous SCT and
myeloablative allogeneic SCT to recommend one option
over the other; both appear to have a survival benefit,
but have competing risks. Comparison of these two
techniques is biased by different patient selection criteria.
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There are currently no data available to make a
recommendation regarding the use of reduced
intensity/nonmyeloalative allogeneic SCT versus
autologous SCT. Comparison of these two techniques is
biased by different patient selection criteria.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
ALLOGENEIC SCT CONDITIONING AND DONOR SOURCE
 Reduced intensity conditioning appears to be an
acceptable alternative approach in allogeneic SCT,
based on one study and expert opinion.
 There are insufficient data to recommend one
conditioning regimen over another for allogeneic SCT.
 In allogeneic SCT, an HLA-matched unrelated donor
appears to be as effective as an HLA-matched related
donor using reduced intensity conditioning, based on
expert opinion.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AREAS OF NEEDED RESEARCH
 Rituximab-based therapy followed by
autologous SCT versus rituximab-based therapy
without SCT.
 Post-autologous SCT rituximab maintenance
therapy versus no post-autologous SCT
maintenance rituximab.
 Ex vivo purged autologous SCT.
 T cell-depleted allogeneic SCT.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AREAS OF NEEDED RESEARCH
 Comparison of matched-related versus
matched-unrelated or other alternative donor
for allogeneic SCT.
 The efficacy and toxicity of reduced intensity
regimens before autologous and allogeneic SCT.
 Reduced intensity allogeneic SCT as salvage
therapy after failed autologous SCT.
 Radioimmunotherapy as part of the preparatory
regimen for autologous SCT or reduced intensity
allogeneic SCT.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
AREAS OF NEEDED RESEARCH
 The impact of radioimmunotherapy and newer
agents (i.e., bendamustine, rituximab,
alemtuzumab, fludarabine, etc.) on stem cell
quality.
 Identification of surrogate molecular markers
pre-SCT that are predictive of long-term survival
in follicular lymphoma patients.
 The association of FLIPI score at diagnosis and at
SCT with prognosis in follicular lymphoma
patients.
ASBMT Evidence-Based Reviews
Follicular Lymphoma
THE EXPERT PANEL:
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Denise M. Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY.
Leo I. Gordon, Northwestern University Feinberg School of Medicine and
the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL.
Jerry King, Blue Cross and Blue Shield of Illinois, Chicago, IL.
Ginna Laport, Stanford University Medical Center, Stanford, CA.
John P. Leonard, Cornell University, Weill Medical College, New York, NY.
Peter McLaughlin, MD Anderson Cancer Center, Houston, TX.
Robert J. Soiffer, Dana Farber Cancer Institute, Boston, MA.
Koen W. van Besien, University of Chicago, Department of Medicine,
Chicago, IL.
Michael Werner, Lymphoma Research Foundation, Chicago, IL.
Roy B. Jones, MD Anderson Cancer Center, Houston, TX.
Philip L. McCarthy, Jr., RPCI, Buffalo, NY.
Theresa Hahn, RPCI, Buffalo, NY.
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy
with Hematopoietic Stem Cell
Transplantation in the Therapy of
Myelodysplastic Syndromes:
An Evidence-Based Review”
Biology of Blood and Marrow Transplantation
(Vol. 15:137-172) January 2009
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
RECOMMENDATIONS
TIMING OF TRANSPLANTATION
Early SCT is recommended for patients who:
 have an IPSS score of INT-2 or high risk
 are considered high risk based on other factors
besides IPSS (i.e., older age, refractory
cytopenias)
 have a suitable donor
 meet the transplant center’s eligibility
requirements
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
PRE-SCT INDUCTION CHEMOTHERAPY
 Insufficient data are available to make a
treatment recommendation for or against
induction chemotherapy
 Decision to use pre-SCT induction therapy
should be made on an individual basis
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
DONOR SELECTION
 Data demonstrate a long-term curative
outcome for related & unrelated allogeneic SCT
 No evidence of a survival advantage based on
donor relation in allogeneic SCT
 An allogeneic HLA-matched donor is
recommended
 Autologous SCT can be considered in the
context of a clinical trial, if an allogeneic donor
is not available
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
TRANSPLANTATION TECHNIQUES
 For low-risk disease, allogeneic BMT and PBSCT
from related donors have equivalent outcomes
 For high-risk disease, there may be a survival
advantage with related donor allogeneic PBSCT
 There is insufficient evidence to recommend
BMT versus PBSCT for unrelated donor allogeneic
SCT
 No evidence of a survival advantage for BMT
versus PBSCT for autologous SCT
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
TRANSPLANTATION TECHNIQUES
 There are insufficient data to:
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Make a recommendation for an optimal
conditioning regimen intensity
 Make a recommendation for any one highdose conditioning regimen over another
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
AREAS OF NEEDED RESEARCH
Important areas of needed research are:
 Benefit of alternative donor sources for patients
without HLA-matched related or unrelated
allogeneic donors
 Role and timing of allogeneic SCT in combination
with hypomethylating and immunomodulatory
regimens
 Randomized trials comparing various novel
agents
 Influence of treatment modalities on quality of life
ASBMT Evidence-Based Reviews
Myelodysplastic Syndromes
EXPERT PANEL MEMBERS:
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Denise M. Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY
Joseph H. Antin, Dana Farber Cancer Institute, Boston, MA
John M. Bennett, University of Rochester, James P. Wilmot Cancer Center,
Rochester, NY
H. Joachim Deeg, Fred Hutchinson Cancer Research Center, Seattle, WA
Christin Engelhardt, Aplastic Anemia and MDS International Foundation,
Churchton, MD
Kathleen V. Heptinstall, The MDS Foundation, Crosswick, NJ
Marcos de Lima, MD Anderson Cancer Center, Houston, TX
Steven D. Gore, Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins, Baltimore, MD
Ronald G. Potts, INTERLINK Health Services, Hillsboro, OR
Lewis R. Silverman, Mt. Sinai School of Medicine, New York, NY
Roy B. Jones, MD Anderson Cancer Center, Houston, TX
Philip L. McCarthy, Jr., RPCI, Buffalo, NY
Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell
Transplantation in the Therapy of Acute
Myeloid Leukemia (AML) in Adults:
An Evidence-Based Review”
Biology of Blood and Marrow Transplantation
(Vol. 14:137-180) January 2008
ASBMT Evidence-Based Reviews
AML in Adults
RECOMMENDATIONS
Transplantation versus Chemotherapy
•
•
•
•
•
A survival advantage for allogeneic SCT for patients under
age 55 with high risk cytogenetics
No survival advantage in patients over age 55 with low risk
cytogenetics
In 2nd complete remission, allogeneic SCT is
recommended
In 2nd complete remission autologous SCT is
recommended if no available allogeneic donor
No significant advantage of autologous SCT over
chemotherapy (studies using modern technologies may
affect this recommendation)
ASBMT Evidence-Based Reviews
AML in Adults
INCONCLUSIVE EVIDENCE
There is insufficient evidence to:
• Routinely recommend allogeneic SCT for
patients with intermediate risk cytogenetics
(although it is a reasonable strategy)
• Recommend reduced intensity conditioning
allogeneic SCT vs. chemotherapy
• Recommend the use of myeloablative regimens
for patients over age 55
ASBMT Evidence-Based Reviews
AML in Adults
RECOMMENDED TECHNIQUES
• Allogeneic SCT with a matched related donor is
recommended if available
• Matched unrelated donor allogeneic SCT using
reduced intensity conditioning may provide equivalent
outcomes to related donor allogeneic SCT
• For high risk disease, allogeneic PBSCT is recommended
over BMT; For low risk disease, allogeneic PBSCT and
BMT have equivalent outcomes
• An HLA-matched related donor SCT is recommended
over autologous SCT
• Autologous PBSCT is recommended over autologous
BMT
ASBMT Evidence-Based Reviews
AML in Adults
INCONCLUSIVE EVIDENCE
There is insufficient evidence to:
• Recommend matched unrelated donor allogeneic
SCT over autologous SCT (ongoing studies reflecting
modern techniques may provide this evidence)
• Recommend purged BMT or PBSCT
• Recommend tandem versus single autologous SCT
• Recommend T cell-depleted grafts from allogeneic
donors
• Recommend PBSCT versus BMT in matched unrelated
donor allogeneic SCT
ASBMT Evidence-Based Reviews
AML in Adults
THERAPY REGIMEN
• Fractionated rather than single dose total body
irradiation is recommended in allogeneic SCT
ASBMT Evidence-Based Reviews
AML in Adults
TECHNIQUES WITH INCONCLUSIVE EVIDENCE
• No difference or preference for any one high
dose therapy conditioning regimen in
autologous SCT
• No difference or preference for any one
myeloablative conditioning regimen in
allogeneic SCT; Studies of late effects may
change this recommendation
• No data on the benefit of reduced intensity
conditioning for allogeneic SCT; regimen
intensity is dependent on patient characteristics
ASBMT Evidence-Based Reviews
AML in Adults
AREAS OF NEEDED RESEARCH
• The role of SCT in treating patients with specific molecular
markers (e.g., FLT3, NPM1, CEBPA, BAALC, MLL, NRAS, etc.)
especially in patients with normal cytogenetics
• The benefit of using SCT to treat different cytogenetic
subgroups
• The impact on survival outcomes of reduced intensity or
nonmyeloablative versus conventional conditioning in
older (> 60 years) and intermediate (40-60 years) aged
adults
• The impact on survival outcomes of unrelated donor SCT
versus chemotherapy in younger (< 40 years) adults with
high-risk disease
ASBMT Evidence-Based Reviews
AML in Adults
THE EXPERT PANEL MEMBERS
•
•
•
•
•
•
•
•
•
•
•
Denise M. Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY
Frederick Appelbaum, Fred Hutchinson Cancer Institute, Seattle, WA
Peter A. Cassileth, University of Miami Sylvester Cancer Center, Miami, FL
Armand Keating, University of Toronto, Toronto, Ontario, Canada
Jamie Kerr, Excellus Blue Cross/Blue Shield, Rochester, NY
Yago Nieto, MD Anderson Cancer Center, Houston, TX
Susan Stewart, BMT Infonet, Chicago, IL
Richard M. Stone, Dana Farber Cancer Institute, Boston, MA
Martin Tallman, Northwestern University Feinberg School of Medicine,
Robert H. Lurie Comprehensive Cancer Center, Chicago, IL
Philip L. McCarthy, Jr., RPCI, Buffalo, NY
Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell
Transplantation in the Therapy of
Acute Myeloid Leukemia (AML) in
Children: An Evidence-Based
Review”
Biology of Blood and Marrow Transplantation
(Vol. 13:1-25) January 2007
ASBMT Evidence-Based Reviews
AML in Children
RECOMMENDATIONS
Transplantation versus Chemotherapy:
• Allogeneic SCT is recommended in 1st complete
remission
• Autologous SCT and chemotherapy in 1st complete
remission are equivalent in outcomes
• In 2nd complete remission, allogeneic SCT is
recommended if a suitable HLA-matched related
donor is available
• An HLA-matched unrelated donor is
recommended in the context of a clinical trial
ASBMT Evidence-Based Reviews
AML in Children
RECOMMENDED TECHNIQUES
• HLA-matched related donor allogeneic SCT
superior to autologous SCT in 1st complete
remission
• In 2nd complete remission, HLA-matched related
or unrelated donor allogeneic SCT is
recommended over autologous SCT
• Purging is not recommended using currently
available purging agents
ASBMT Evidence-Based Reviews
AML in Children
INDICATIONS FOR SCT
•
•
•
•
•
HLA-matched related donor allogeneic SCT is preferred in
1st or 2nd complete remission
In 2nd complete remission, alternative donors could be
considered if an HLA-matched related allogeneic donor is
not available
No evidence of a benefit of SCT for Acute Promyelocytic
Leukemia (APL) in 1st complete remission
Allogeneic SCT is preferred for APL in 2nd complete
remission
Autologous SCT is recommended for APL in 2nd complete
remission if no suitable HLA-matched related, unrelated, or
alternative allogeneic donor is available
ASBMT Evidence-Based Reviews
AML in Children
TECHNIQUES WITH INCONCLUSIVE EVIDENCE
• No data to recommend related versus unrelated
allogeneic SCT
• No recommendation can be made for preferred
techniques for unrelated SCT
• No difference or preference for one
myeloablative conditioning regimen over
another
ASBMT Evidence-Based Reviews
AML in Children
AREAS OF NEEDED RESEARCH
• The role of risk group stratification, including the role of
cytogenetics, in selection of patients for allogeneic SCT,
especially those in 1st complete remission
• The appropriate timing and use of alternative donor SCT,
given that matched unrelated donor SCT appears to yield
outcomes equivalent to matched related donor SCT
• The role of reduced intensity SCT and/or other
immunomodulatory approaches to maximize the graftversus-leukemia effect
• The role of biologically targeted agents in the treatment
of AML, including induction, consolidation, conditioning
regimen, and post-SCT
ASBMT Evidence-Based Reviews
AML in Children
THE EXPERT PANEL MEMBERS
Denise M. Oliansky, Roswell Park Cancer Institute (RPCI), Buffalo, NY
J. Douglas Rizzo, Medical College of Wisconsin, Milwaukee, WI
Peter D. Aplan, NIH, NCI, CCR, Genetics Branch, Bethesda, MD
Robert J. Arceci, Kimmel Comprehensive Cancer Center, Baltimore, MD
Louis Leone, Children’s Oncology Group, Arcadia, CA
Yaddanapudi Ravindranath, Children’s Hospital of Michigan and Wayne
State University School of Medicine, Detroit, MI
Jean E. Sanders, Fred Hutchinson Cancer Research Center, University of
Washington, Seattle, WA
Franklin O. Smith III, Cincinnati Children’s Hospital and Medical Center and
University of Cincinnati College of Medicine, Cincinnati, OH
Fiona Wilmot, Blue Shield of California, San Francisco, CA
Philip M. McCarthy Jr., RPCI, Buffalo, NY
Theresa Hahn, RPCI, Buffalo, NY
ASBMT Evidence-Based Reviews
“The Role of Cytotoxic Therapy with
Hematopoietic Stem Cell
Transplantation in the Therapy of
Multiple Myeloma: an EvidenceBased Review.”
Biology of Blood and Marrow Transplantation
(Vol. 9:4-37) January 2003
ASBMT Evidence-Based Reviews
Multiple Myeloma
RECOMMENDATIONS
Transplant is:
 Recommended as de novo therapy
 Equivalent as de novo or salvage, but de novo
is preferred
ASBMT Evidence-Based Reviews
Multiple Myeloma
RECOMMENDED TECHNIQUES
 Autologous SCT is preferred over allogeneic SCT
 Autologous PBSCT is preferred over autologous
BMT
 Melphalan conditioning regimen is preferred to
melphalan combined with total body irradiation
Studies are ongoing to evaluate allogeneic transplant
ASBMT Evidence-Based Reviews
Multiple Myeloma
RECOMMENDED TECHNIQUES
 Autologous PBSCT using CD34+ selected or
unselected stem cells are equivalent in
efficacy
ASBMT Evidence-Based Reviews
Multiple Myeloma
TECHNIQUE NOT RECOMMENDED
 Autologous purged bone marrow transplantation
is not recommended
ASBMT Evidence-Based Reviews
Multiple Myeloma
TECHNIQUES WITH INCONCLUSIVE EVIDENCE
Recommended for comparative study:
 Transplant versus chemotherapy as salvage
therapy
 Preferred conditioning regimen for allogeneic
myeloablative and non-myeloablative
transplants
 Maintenance therapy post-autologous
transplant
ASBMT Evidence-Based Reviews
Multiple Myeloma
TECHNIQUES WITH INCONCLUSIVE EVIDENCE
Not recommended for comparative study:
 Tandem autologous transplant – studies are
ongoing
 Transplant as a high-dose sequential regimen
 Allogeneic BMT versus PBSCT
ASBMT Evidence-Based Reviews
Multiple Myeloma
AREAS OF NEEDED RESEARCH
• Maintenance therapy post-transplantation with
nothing vs. interferon alpha vs. other agents
such as corticosteroids, thalidomide or its
derivatives
ASBMT Evidence-Based Reviews
Multiple Myeloma
THE EXPERT PANEL MEMBERS
 Theresa Hahn, PhD, Roswell Park Cancer Institute, Buffalo, N.Y.
 John Wingard, MD, University of Florida College of Medicine, Gainesville
 Kenneth C. Anderson, MD, Dana-Farber Cancer Institute, Harvard Medical
School, Boston
 William I. Bensinger, MD, Fred Hutchinson Cancer Research Center, Seattle
 James R. Berenson, MD, Cedars Sinai Medical Center, Los Angeles
 Greg Brozeit, International Myeloma Foundation, Hollywood, Calif.
 Joseph R. Carver, MD, Abramson Cancer Research Institute, University of
Pennsylvania, Philadelphia
 Robert A. Kyle, MD, Mayo Clinic, Rochester, Minn.
 Philip L. McCarthy, MD, Roswell Park Cancer Institute, Buffalo, N.Y.
ASBMT Evidence-Based Reviews
Steering Committee Members
 Chair, Roy Jones, MD, MD Anderson Cancer Center,
University of Texas, Houston
 Vice Chair, Bipin Savani, MD, Vanderbilt University,
Nashville, TN
 Yago Nieto, MD, MD Anderson Cancer Center,
University of Texas, Houston
 Douglas Rizzo, MD, Medical College of Wisconsin,
Milwaukee
 Donna Wall, MD, University of Manitoba/CancerCare
Manitoba, Winnipeg, Canada
 John Wingard, MD, University of Florida College of
Medicine, Gainesville
ASBMT Evidence-Based Reviews
More Information
Reviews and
ASBMT Position Statements
available at
www.asbmt.org
ASBMT Evidence-Based Reviews
The American Society for
Blood and Marrow
Transplantation
A national professional association
of clinicians and researchers
promoting advancement of the
field of blood and bone marrow
transplantation and the highest
standards of patient care.