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In the News
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DLBL, relapsed - BjH, 2007:
Non-myeloablative (mini) allogeneic stem
cell transplantation
for relapsed diffuse large B-cell lymphoma: a multicentre
experience
"Patients with DLBCL who relapse
after, or are ineligible for, autologous HCT have a poor
prognosis with conventional therapy. This study provides
evidence that non-myeloablative allogeneic HCT is an effective
salvage therapy which can produce long-term disease-free
survival in a subset of these patients. Given that virtually
none of these patients would be expected to achieve durable
disease-free survival with conventional therapy, the rate of PFS
seen after non-myeloablative allogeneic HCT is encouraging and
provides proof of the principle that immunological GVL effects
alone can control DLBCL in some cases."
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Be The Match -
Patients Connect Facebook Page
People can join the Be The Match
Registry® – the world’s largest listing
of potential marrow donors and donated cord blood units –
contribute financially and volunteer.
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Overview
Excellent videos explain the history of stem cell rescue, when it's
needed, what it is, and how it's improved over time.
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NEW: Be the Match
The Donor Selection & Transplant Process
marrow.org
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A
stem cell transplant* may sometimes be medically necessary
for patients with lymphomas.
With a stem cell transplant, the
stem cells** obtained from bone marrow,
peripheral blood, or umbilical cord blood are given back to the
patient following high dose treatment, which can damage or ablate
(kill off) these vital cells. The engrafted stem cells
can then restore bone marrow
function** impaired or destroyed by the high dose conditioning
therapy.
A stem cell transplant is sometimes called a bone
marrow transplant.
*The terms stem cell transplant,
infusion,
rescue, engraftment, or support may be used
interchangeably and essentially have the same meaning.
** Stem cells are "immature cells
known as hematopoietic or blood-forming stem cells.
Hematopoietic stem cells divide to form more blood-forming stem
cells, or they mature into one of three types of blood cells:
white
blood cells, which fight
infection;
red
blood cells, which carry oxygen; and
platelets,
which help the blood to clot.
Most hematopoietic stem cells are
found in the bone marrow, but some cells, called peripheral
blood stem cells (PBSCs), are found in the bloodstream. Blood in
the umbilical cord also contains hematopoietic stem cells. Cells
from any of these sources can be used in transplants" [in
order to restore bone marrow function.]
Cancer.gov
The different types of stem cell
transplants are named from the origin of the stem cells:
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autologous - stem cells harvested from self
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allogeneic - stem cells harvested from donor
(following reduced for full intensity therapy)
syngeneic - stem cells harvested from identical twin
cord blood - stem cells from saved cord
blood, from self or donor |
Notes:
allogeneic and autologous are the two main types of stem
cell transplantation (or rescue). Allogeneic stem cells are
derived from a matched donor (such as a sibling); in the autologous
type, stem cells are derived from the patient. Each type has
unique risks and benefits, and which is preferred can depend on the
clinical details. See for example, Comparing
SCT types
About
conventional allogeneic stem cell transplant
In this therapy stem cells from an HLA compatible donor are
harvested, stored and then engrafted into the patient after the patient receives high
doses of chemotherapy and/or radiotherapy conditioning therapy.
The stem
cells can be obtained from a related or unrelated donor. The cells may
be 'harvested"
from the donor's bone marrow through a surgical procedure, or acquired
from the
donor's peripheral
blood.*
* The latter
method of obtain stem cells has become more common. peripheral blood stem cell transplant, PBSCT
The goal of transplant therapy is to
restore or rescue hematologic and immunologic function following high
dose therapy.
The stem cells are of a type that can develop into the full range of
blood and immune cells.
Typically allogeneic transplants have
three phases:
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Donor
matching phase - cells from potential donors are tested
for compatibility.
* MUD is- a common abbreviation used. It means Matched
Unrelated Donor.
The donor experience?
Potential donors are asked a
series of questions to make sure they are healthy enough to donate
and don’t pose an unacceptable risk of infection to the
recipient.
"Risks for donors are minimal, and serious
complications are rare. Problems such as sore throat or nausea may
be caused by anesthesia."
ASC
See for details
Harvesting Stem Cells
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Conditioning
phase - use of high dose therapies to eradicate the disease.
Myeloablative
means that the treatment kills (ablates) the myeloid stem cells in
the bone marrow - the cells that produce new blood cells.
"Once you are ready to begin the transplant protocol, you are admitted to the hospital for high doses of chemotherapy and/or radiation therapy for what is called “conditioning.” This conditioning phase can take
five to 10 days and is completed a day or two before the infusion of the stem cell product.
The purpose of conditioning is to give high enough doses of chemotherapy and/or radiation to eliminate any
cancerous cells that are present, to make room for the new cells, and to destroy your immune system. This is done to prevent rejection of the new donor cells. Please refer to the transplant section for further discussion of the conditioning
regimen." 7 Source:
cancer.med.umich.edu
NOTE: A mini transplant is often called a non-ablative or
non-myeloablative
transplant,
because
the conditioning treatment is less intense and does not ablate stem cells in the bone marrow.
How to make stem cell transplantation less toxic
http://bit.ly/8SL7qD
"In the protocol, published in the Lancet journal, TBI and
standard chemotherapeutic doses were replaced by monoclonal
antibodies"
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Engraftment
phase - the stem cells from a donor are given back to the patient
to reconstitute the immune system. Sometimes purging techniques
are used to clean the stem cells of residual tumor cells prior to
engraftment, or shortly after.
Approximately two to four weeks after your transplant you can
expect to see signs of your bone marrow “engrafting” or
beginning to grow. The first sign of this is the production of
white blood cells. Platelets often take a little longer to begin
developing. Once you have “engrafted” and your condition is
stable, you will be discharged from the hospital. 7
Source: cancer.med.umich.edu
Potential Advantages of Allo
Transplants
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Tumor free graft |
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Undamaged Stem Cells |
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Avoidance of MDS/secondary AML |
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Graft versus lymphoma effect |
Potential Problems with Allo
Transplants
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Lack of suitable donors |
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High Treatment Related Mortality
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Regimen related toxicity |
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Infection |
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Graft
versus Host Disease (See GVHD for
details)
(not a risk for auto SCT type) |
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Adapted from: Allogeneic
Transplantation in Lymphoma
File Format: Microsoft Powerpoint 97 View
as HTML
About Donor Lymphocyte Infusions
Patients with lymphoma in relapse after allogeneic
stem cell transplantation can be treated by infusing leukocytes from
the original stem cell donor with the goal of enhancing the graft
versus lymphoma effect.
Resources:
About HLA Typing
TOPIC
SEARCH: PubMed
| Web
HLA stands for Human Leukocyte
Antigens. These proteins are unique markers found on the
surface of nearly every cell in the body, and are in especially high
concentrations in white blood cells.
Like a fingerprint, HLA proteins enable
your immune system to distinguish between cells that belong in our
body and cells that do not.
HLA typing is important because finding
a matched donor reduces the risk of developing graft rejection
and acute
Graft versus Host Disease or the graft
could be rejected (Graft rejection) by the patient’s immune
system.
So the goal is to obtain as close a
donor-recipient match of HLA as possible, without undue delay.
The ideal candidates for a match are siblings, perhaps of the same sex
and blood type. Blood is drawn and white blood cells are
isolated from the sample.
"The odds of finding
“matches” between siblings greatly increases compared to the
general population because we have a 1-in-4 chance of being
identical to each sibling."6
Two tests are available to determine a person's
HLA type: serological typing and molecular (DNA) typing. Although
serological typing is usually sufficient to determine if a patient
and a sibling have the same HLA type, molecular typing gives more
detailed results. Thus, when searching for an unrelated donor,
molecular typing is recommended. Molecular typing enables the
NMDP to more quickly and accurately identify matches.
Note: transplants can be successful with a less than
perfect match. If there is no perfect match, the doctor may want to do
a mismatched donor transplant, depending on the patient's age, disease
and other factors. 1
Six HLA-factors (alleles)
Alleles are variant forms of
the same gene that determine our characteristics.
A, B, C,
DRB1, DRB3-5, DQB1
Five most important: A, B, C, DRB1, and HLA-DQB1
The minimum acceptable match was
originally required at least 5 matches, ie, a 5 of 6 match.
Although the required level of resolution has evolved over the years,
the basic minimum requirement for a 5 of 6 match has not changed.
This is because there are abundant data to show that HLA matching at
this minimum level can lead to successful transplantation outcomes.
However, it is also clear that transplantation outcomes can be
improved by matching strategies that increase the degree of HLA
compatibility above the minimum. 1
Non-HLA Factors
These factors may be considered when
donors are selected
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cytomegalovirus
(CMV)—negative serology (for patients with CMV-negative
serology) |
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male
sex |
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younger
age |
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ABO
(blood type) compatibility |
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larger
body weight |
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matched
race 1
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Bone Marrow Transplantation
(BMT) and Peripheral Blood Stem Cell (PBS) Transplantation
Questions and Answers cancer.gov
1)
What are bone marrow and hematopoietic stem cells? Cancer.gov
2) What are bone marrow transplantation and peripheral
blood stem cell transplantation? Cancer.gov
3) Why are transplants used in cancer treatment? Cancer.gov
4) What types of cancer are treated? Cancer.gov
5) How are the donor’s stem cells matched to the
patient’s stem cells in allogeneic or syngeneic transplantation? Cancer.gov
6) How is bone marrow obtained for transplantation? Cancer.gov
7) How are peripheral
blood stem cells (PBSCs) obtained for transplantation? Cancer.gov
8) How are umbilical cord stem cells obtained for
transplantation? Cancer.gov
9) Are any risks associated with donating bone marrow? Cancer.gov
10) Are any risks associated with donating PBSCs? Cancer.gov
11) How does the patient receive the stem cells during the
transplant? Cancer.gov
12) Are any special measures taken when the cancer patient is also the
donor (autologous transplant)? Cancer.gov
13) What happens after the stem cells have been transplanted to the
patient? Cancer.gov
14) What are the possible side effects of BMT and PBSCT? Cancer.gov
15) What is a “mini-transplant”? Cancer.gov
16) What is a “tandem transplant”? Cancer.gov
17) How do patients cover the cost of BMT or PBSCT? Cancer.gov
18) What are the costs of donating bone marrow, PBSCs, or umbilical
cord blood? Cancer.gov
19) Where can people get more information about potential donors and
transplant centers? Cancer.gov
Resources
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Bone Marrow Transplant (BMT)
makna.org
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National marrow donor program HLA-matching guidelines for
unrelated marrow transplants bbmt.org
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Advances in HLA Typing (for physicians) marrow.org
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Searching for a Donor Through the NMDP bmtinfonet.org
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The donor experience ASC
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Infections Post-Transplant: Antibiotic prophylaxis with
meropenem after allogeneic stem cell transplantation nature.com
(2003)
Resources on Allogeneic Transplantation
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Comprehensive Checklist: Before, During, After Allo SCT: uwhealth.org
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Allogeneic vs Autologous Transplantation for Indolent Non
Hodgkin's Lymphoma, Bruce Cheson, MD National Cancer Institute John G. Gribben, MD Harvard Medical School
PAL/Healthology
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Allogeneic Bone Marrow Transplantation in Patients With
Sensitive Low-Grade Lymphoma or
Mantle Cell Lymphoma Biology of
Blood and Marrow Transplantation 7:561-567 (2001)
Abstract-WEB
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Highly recommended: Search
for Stem cell Transplant Centers BMTinfoNet
Also provides: background, Number of Transplants
done,
Minimum Donor Match Criteria, Contacts, Support Groups Available
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Support group for SCT: ACOR BMT-Talk Support
Groups
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Patient SCT Stories - Cyberfamily
| What to take to Hospital Cyberfamily
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Research News
Scholar Search
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An allo SCT (from a donor) is
thought to have very good curative
potential, even for indolent lymphoma –
but sometimes the lymphoma returns.
A discovery provides a
potential way to improve the result
http://bit.ly/9gYdMq
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Allogeneic stem cell
transplantation in follicular lymphoma: recent progress and
controversy
http://bit.ly/9QY8aa
"Allogeneic stem cell transplantation (allo HCT)
is a curative treatment for follicular lymphoma, but is hampered
by a relatively high treatment-related mortality and by
difficulties in identifying high-risk groups for whom transplant
is warranted." |
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Mini-allo
SCT for relapsed DLBC Lymphoma: a multicentre experience
http://bit.ly/a8hDdq
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How to make stem cell transplantation less toxic
http://bit.ly/8SL7qD
"In the protocol, published in the Lancet journal, TBI
and standard chemotherapeutic doses were replaced by monoclonal
antibodies"
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GVHD: Prochymal, no better than a
placebo in two final trials. http://bit.ly/BkDo9
Osiris said Tuesday preliminary results for two
Phase III trials evaluating Prochymal for the treatment of acute
graft versus host disease showed no statistical difference between
the drug and a placebo in either trial. Osiris said Prochymal did
show significant improvements in response rates in
difficult-to-treat liver and gastrointestinal graft versus host
disease even as it failed to meet its primary endpoint in both
trials.
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Outcome report: 8-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide and rituximab.
Blood. 2008 Apr 14; PMID: 18411419
Forty-seven patients were included. All patients experienced
complete remission, with only 2 relapses. With a median follow-up
time of 60 months (range, 19-94), the estimated survival and
progression-free survival rates were 85% and 83%, respectively.
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Outcome report: Long-term
outcomes after reduced-intensity conditioning allogeneic stem cell
transplantation for low-grade lymphoma: a survey by the French
Society of Bone Marrow Graft Transplantation and Cellular Therapy
(SFGM-TC). Haematologica. 2007 May;92(5):627-34 PMID:
17488686
In patients in CR, PR and chemoresistant disease, the 3-year
overall survival rates were 66%, 64% and 32%, respectively, while
the 3-year event-free survival rates were 66%, 52% and 32%,
respectively. The 3-year cumulative incidences of TRM were 32%,
28% and 63%, respectively. The incidence of relapse was 9.6%.
INTERPRETATION AND CONCLUSIONS: Although associated with
significant TRM, RIC allogeneic SCT in advanced chemosensitive
disease leads to long-term survival.
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Review: T cell therapies
following hematopoietic stem cell transplantation: surely
there must be a better way than Donor Lymphocyte Infusion (DLI) ?
nature.com
pdf
Advances in the past few years have significantly improved
adoptive immunotherapy strategies available following autologous
and allogeneic hematopoietic stem cell transplantation (HSCT).
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Chimera: from bane to blessing bloodjournal.org
"New data suggest that a mild preparative regimen of
antibodies that block CD40 ligand and deplete host NK
cells may make allogeneic hematopoietic stem cell
transplants safe, establish long-term immunologic
tolerance, and broaden the applicability of cord blood
as a source of stem cells by making engraftment more
efficient."
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Safer Allos? The Immune "Character" of Allogeneic Hematopoietic Transplants CME
Medscape
(free login req.)
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New marrow transplant method developed at Stanford may
eliminate fatal side effects [of GVHD] eurekalert.org
Dec 2004
By increasing the relative amount of these cells
[regulatory t-cells], he found that he could retain the desired
effect of killing cancerous cells following bone marrow
transplantation, but eliminate the attack on host tissues.
"It allows you to throw out the one effect but not the
other," he said.
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Long-term disease-free survival of patients with advanced
follicular lymphoma after allogeneic bone marrow transplantation.
Br J Haematol. 2004 Nov;127(3):311-21 PMID:
15491292 | Related
articles
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The allogeneic effect in non-Hodgkin's lymphoma.
Leuk Lymphoma. 2003;44 Suppl 3:S91-7. Review PMID:
15202531 | Related
articles
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Allo SCT & GVHD: Impact of transplanted CD34+ cell dose in
allogeneic unmanipulated peripheral blood stem cell
transplantation. Bone Marrow Transplant. 2003 Jun; 31(11):
967-72 PMID: 12774046
| Related articles
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Treatment of advanced
mycosis fungoides by allogeneic stem-cell transplantation with a
nonmyeloablative regimen. Bone Marrow Transplant. 2003
Apr;31(8):663-6. PMID: 12692606 PubMed
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Outcome report: Allogeneic hematopoietic stem cell
transplantation for progressive follicular lymphoma.
Bone Marrow Transplant. 2002 Jun;29(12):973-8. PMID: 12098065 PubMed
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Outcome report: Allogeneic stem-cell transplantation for
lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine)
conditioning combined with post-transplant donor-lymphocyte infusion.
Cytotherapy. 2001;3(3):203-10.
PMID: 12171727 PubMed
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OPTIMIZING: The clinical significance of human
leukocyte antigen (HLA) allele compatibility in patients receiving a
marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched
unrelated donors. Blood. 2002 Jun 1;99(11):4200-6.
PMID: 12010826 PubMed
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