HLA Typing | Phases
Relapse after allogeneic transplant | Donor Lymphocyte
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Excellent videos explain the history of stem cell rescue, when it's
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The Donor Selection & Transplant Process
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
A stem cell transplant is sometimes called a bone
*The terms stem cell transplant,
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:
blood cells, which fight
blood cells, which carry oxygen; and
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.]
The different types of stem cell
transplants are named from the origin of the stem cells:
autologous - stem cells harvested from self
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
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
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.
cells can be obtained from a related or unrelated donor. The cells may
from the donor's bone marrow through a surgical procedure, or acquired
* 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
The stem cells are of a type that can develop into the full range of
blood and immune cells.
LymphoMom (on the
forum) describes the reduce-intensity allogeneic transplant
The mini-allo is sometimes also
referred to as non-myeloablative, or reduced intensity. Just like
Andy, it's what my son had as well. In fact it's becoming
increasingly more common based on the type of lymphoma.
A traditional Bone Marrow Transplant
(BMT) was myeloablative, meaning the conditioning chemo totally
destroys the cells in the patient's bone marrow, and the new donor
stem cells are infused (engrafted) in later. The advantage of
the myeloablative type is that it destroys the diseased bone marrow,
and the chemo is typically strong enough to destroy any residual
disease. The downside is that it has a high treatment related
mortality (somewhere around 30-35%), and usually reserved for young,
(also called Reduced Intensity)
doesn't completely destroy the bone marrow. It prepares it for the
new stem cell graft, and then the patient goes through an extended
period of time in what is called mixed chimerism. It means the bone
marrow is part donor, part patient. It slowly converts over time to
full donor....or at least that is the intent. Why it can work well
is that the transplant works with what is called a Graft vs Lymphoma
effect. That means transplant works not just from the chemo blowing
away the old disease, but the new bone marrow actually fights the
disease. The advantage of the mini is that it has less treatment
related mortality (about 15% vs the 35%). The disadvantage is that
it comes with a higher rate of relapse.
A Haploidentical (haplo) means half
identical. When talked about donor matching, there are usually 8 or
10 factors the doctors look at in matching. For example my son had a
10/10 match. For people with less than a perfect match, a haplo
takes a half identical match. It's a first degree relative, like
parent, sibling or child. If the first degree relative isn't a
perfect match (25% chance it will be), the next best thing is a half
match. Haplos are becoming more safe and popular and are opening up
transplants to people who wouldn't otherwise have a donor. I asked
our doctor his opinion on Haplos and he said he would first prefer a
10/10 match, but he would prefer a haplo over a 9/10 match. So just
to reiterate, a haplo isn't the same thing as a mini transplant.
Haplo refers to the donor matching type, and mini or reduced refers
to the type of conditioning used.
The doctors carefully choose which transplant is best for the
patient. A lot depends on the underlying health of the patient, the
disease status, and of course the disease itself. Some types of
lymphoma have a better proven Graft vs Lymphoma (GVL) effect than
others. For example with my son's PTCL, even though it has a poor
rate of response to chemo in general, it does have an excellent GVL
effect making a mini transplant a really good option.
Also, a mini isn't black and white - it's more of a spectrum of
conditioning. The doctors can choose to make it more or less
ablative depending on what they think is best.
I also want to emphasize that even
though the transplant is called "mini", there's nothing mini about
it. Having gone through it (and we are on day 88), it's the most
difficult medical treatment I've seen. Manageable, doable, but
serious stuff. I think the term mini sounds misleading, it's
anything but, IMHO.
Typically allogeneic transplants have
donor matching, conditioning, and engraftment
matching phase - in this phase the cells from potential donors are tested
* MUD is- a common abbreviation used. It means Matched
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
"Risks for donors are minimal, and serious
complications are rare. Problems such as sore throat or nausea may
be caused by anesthesia."
See for details
Harvesting Stem Cells
phase - use of high dose therapies to eradicate the disease.
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:
NOTE: A reduced
intensity (or mini) transplant is also called a non-ablative or
the conditioning treatment is less intense and does not ablate
all of the cells in the bone marrow.
How to make stem cell transplantation less toxic
"In the protocol, published in the Lancet journal, TBI and
standard chemotherapeutic doses were replaced by monoclonal
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
Potential Advantages of Allo
Tumor free graft
Undamaged Stem Cells
Avoidance of MDS/secondary AML
Graft versus lymphoma effect
Potential Problems with Allo
Lack of suitable donors
High Treatment Related Mortality
Regimen related toxicity
versus Host Disease (See GVHD for
(not a risk for auto SCT type)
Adapted from: Allogeneic
Transplantation in Lymphoma
File Format: Microsoft Powerpoint 97 View
Relapse after allogeneic transplant
Therapeutic options for patients with lymphoma who
relapse after allogeneic stem cell transplantation are expanding.
Delay in relapse and age can influence the opportunity to benefit
from subsequent therapy.
Testing protocols after allogeneic transplant
for relapsed lymphoma OR CLL
Testing immunotherapy - CART 19 in Chemotherapy relapsed/
refractory cd19 Lymphoma - prior transplant may be eligible
Relapse after allogeneic stem cell transplantation
Relapse of lymphoma after allogeneic hematopoietic cell
Management strategies and outcome
can control lymphoma with acceptable morbidity. Particularly for
patients with later relapse, ongoing treatment after relapse can
yield meaningful benefit and prolonged survival.
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.
About HLA Typing
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
Graft versus Host Disease or the graft
could be rejected (Graft rejection) by the patient’s immune
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
These factors may be considered when
donors are selected
(CMV)—negative serology (for patients with CMV-negative
(blood type) compatibility
Bone Marrow Transplantation
(BMT) and Peripheral Blood Stem Cell (PBS) Transplantation
Questions and Answers cancer.gov
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
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
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
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
Bone Marrow Transplant (BMT)
National marrow donor program HLA-matching guidelines for
unrelated marrow transplants bbmt.org
Advances in HLA Typing (for physicians) marrow.org
Searching for a Donor Through the NMDP bmtinfonet.org
The donor experience ASC
Infections Post-Transplant: Antibiotic prophylaxis with
meropenem after allogeneic stem cell transplantation nature.com
Resources on Allogeneic Transplantation
Comprehensive Checklist: Before, During, After Allo SCT: uwhealth.org
Allogeneic vs Autologous Transplantation for Indolent Non
Hodgkin's Lymphoma, Bruce Cheson, MD National Cancer Institute John G. Gribben, MD Harvard Medical School
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)
Highly recommended: Search
for Stem cell Transplant Centers BMTinfoNet
Also provides: background, Number of Transplants
Minimum Donor Match Criteria, Contacts, Support Groups Available
Support group for SCT: ACOR BMT-Talk Support
Patient SCT Stories - Cyberfamily
| What to take to Hospital Cyberfamily
* BMT 2014: “Allogeneic
hematopoietic cell transplantation for diffuse large B cell lymphoma: who,
when and how?” http://bit.ly/1eyiWiF
Speaks to an urgent unmet need and novel
approaches. Encouraging that pd-1 antibody was noted as a possible advance
- as I wasn't sure if I was overestimating the significance of the recent
report by Leo Gordon's group on pd1 consolidation after transplant. No
mention of CART 19 ... which is another very promising approach for patients
with lymphoma refractory to chemo. (Karl)
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
Allogeneic stem cell
transplantation in follicular lymphoma: recent progress and
"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
SCT for relapsed DLBC Lymphoma: a multicentre experience
How to make stem cell transplantation less toxic
"In the protocol, published in the Lancet journal, TBI
and standard chemotherapeutic doses were replaced by monoclonal
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
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.
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:
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.
Review: T cell therapies
following hematopoietic stem cell transplantation: surely
there must be a better way than Donor Lymphocyte Infusion (DLI) ?
Advances in the past few years have significantly improved
adoptive immunotherapy strategies available following autologous
and allogeneic hematopoietic stem cell transplantation (HSCT).
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
Safer Allos? The Immune "Character" of Allogeneic Hematopoietic Transplants CME
(free login req.)
New marrow transplant method developed at Stanford may
eliminate fatal side effects [of GVHD] eurekalert.org
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.
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
The allogeneic effect in non-Hodgkin's lymphoma.
Leuk Lymphoma. 2003;44 Suppl 3:S91-7. Review PMID:
15202531 | Related
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
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
Outcome report: Allogeneic hematopoietic stem cell
transplantation for progressive follicular lymphoma.
Bone Marrow Transplant. 2002 Jun;29(12):973-8. PMID: 12098065 PubMed
Outcome report: Allogeneic stem-cell transplantation for
lymphoproliferative disorders using BEAM-CAMPATH (+/- fludarabine)
conditioning combined with post-transplant donor-lymphocyte infusion.
PMID: 12171727 PubMed
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
In the News
ASCO 2014: Allo
SCT in a cohort of 314 advanced lymphoma patients.
Cancer Biol Med.
Reduced-intensity conditioning allogeneic stem
cell transplantation in
malignant lymphoma: current status
DLBL, relapsed - BjH, 2007:
Non-myeloablative (mini) allogeneic stem
for relapsed diffuse large B-cell lymphoma: a multicentre
"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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