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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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Background:
Excellent videos explain the history of stem cell rescue, when
it's needed, what it is, and how it's improved over time.
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
 About
mini allogeneic transplant This is
an allogeneic transplants with reduced intensity conditioning,
using less toxic doses of chemotherapy to prepare for the
transplant.
It
relies instead on the killing action of the donor’s immune cells to
eradicate the remaining disease. This is sometimes called the Graft vs. Disease
(GVD) effect. Click image for an overview of this
treatment.
A mini transplant has many names:
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Reduced
intensity Transplant |
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non-ablative or non-myeloablative
transplant, |
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Adoptive
immunotherapy.
"Non-myeloablative",
because the conditioning therapy does not fully ablate (kill off) the bone marrow
myeloid cells prior to the engraftment or transplant phase of
therapy. |
...."adoptive
immunotherapy", because the donor immune cells act against the
disease - a graft versus lymphoma affect.
Concept of graft versus lymphoma
effect
"The concept of utilizing enhanced immunosuppression rather than
myeloablative cytotoxic conditioning has allowed the engraftment
(acceptance) of allogeneic stem cells from related and unrelated donors with
lower early transplant-related mortality (TRM) and morbidity.
This approach shifts tumor eradication to the graft-vs-host immune
response directed against minor histocompatibility antigens expressed
on tumor cells.
This is not without risk, as the long-term effects
of graft-versus-host disease (GVHD), it’s treatment, or
resulting complications and immunodeficiency may be life threatening.
However, this approach does allow the application of a
potentially curative procedure to elderly or medically infirm
patients who would not tolerate high-dose conditioning regimens."
-
Asheducationbook.org
Chimerism,
a term used often in connection with mini-transplants, means the coexistence
of donor and recipient cells.
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 and Research News:
This study compares outcome of reduced-intensity conditioned transplant
(RIT) with outcome of conventional non-transplant therapy in patients with
Hodgkin's lymphoma relapsing following autograft.
There were 72 patients in two groups who had relapsed, and received salvage
therapy with chemotherapy radiotherapy.
One group (n=38) then underwent alemtuzumab-containing RIT. The second
group-historical controls (n=34), relapsing before the advent of RIT-had no
further high-dose therapy.
This group was required to respond to salvage therapy and live for over 12
months post-relapse, demonstrating potential eligibility for RIT, had this
been available.
Overall survival (OS) from diagnosis was superior following RIT
(48% at 10 years versus 15% ; P=0.0014),
as was survival from autograft
(65% at 5 years versus 15% ; P0.0001).
For the RIT group, OS at 5 years from allograft was 51% , and in chemoresponsive patients was 58% , with current progression-free survival of
42% .
Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions
(DLI) for relapse/progression, with durable remission in five patients at
median follow-up from DLI of 45 months (28-55).
These data demonstrate the potential efficacy of RIT in heavily pre-treated
patients whose outlook with conventional therapy is dismal, and provide
evidence of a clinically relevant graft-versus-lymphoma effect.
full text:
www.nature.com
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Expert Background: Reduced-Intensity Regimens in Allogeneic
Stem-Cell Transplantation for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
asheducationbook
2006 pdf |
Summary: The current data collectively suggest that addition of anti-CD20 monoclonal antibodies significantly improves the
outcome of autologous SCT in patients with NHL who have chemosensitive disease (Table 3). It is recommended for
patients with DLCL or Follicular Lymphoma undergoing their first relapse
and MCL during first remission, but not in patients with CLL.
[Lay comment: But not necessarily the standard of care for any
histology.]
A significant Graft versus Lymphoma effect can be achieved clinically through the use of non-myeloablative transplantation in
patients with chemo-sensitive advanced disease. Yet the applicability
of non-myeloablative SCT appears dependent on disease histologic type, individual patient, and disease
characteristics. The current data suggest an increased risk of relapse with the use of alemtuzumab.
Randomized studies may allow the comparison of various non-myeloablative transplantation strategies. High-dose conditioning regimens
should be considered for patients with chemo-refractory (resistant)
disease who are young and have a good performance status. The field offers significant opportunity for clinical research,
and we strongly encourage participation in clinical trials whenever possible.
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Outcomes:
"Mini"
Allogeneic stem cell transplantation can induce durable clinical
and molecular remissions in relapsed lymphomas: pre-transplant
disease status and histotype heavily influence outcome.
Abstract
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The results show that frequencies were as follows: cumulative
NRM at 3 years, 14%; acute and chronic graft-versus-host disease
(GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69%
for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058);
and 3-year relapse incidence, 29, 31, 35 and 81%, respectively
(P<0.001). Relapse risk differed significantly at 3 years
between follicular lymphoma (FL) and chronic lymphocytic leukemia
(CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94
and 40% (P=0.002) of patients with FL and CLL, respectively. On
multivariate analysis, OS was influenced by chemorefractory
disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and
acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and
effective salvage strategy in both indolent and aggressive NHL.
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Cure word used:
Mini-BMT:
follicular Non-Hodgkin's Lymphoma Cure?
www.webmd.com
83% in Complete Remission 5 to 9 Years After Mini-BMT for
Follicular Lymphoma |
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Reduced-Intensity Conditioning Regimens for Hematologic
Malignancies:
asheducationbook.org
What Have We Learned over the Last 10 Years? (2005) , Sergio
Giralt |
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Non-Myeloablative Transplantation (2002)
asheducationbook.org
David G. Maloney, Brenda M. Sandmaier, Stephen Mackinnon and
Judith A. Shizuru |
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According to a recent article published in the Journal
of Clinical Oncology, "mini"
allogeneic stem cell transplants may provide a chance for a cure for
patients over 60 years of
age with poor-prognosis myeloid (blood) malignancies.
cancerconsultants.com
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Nonmyeloablative (mini) Allogeneic Stem-Cell Transplantation for Hematologic Malignancies: A Systematic Review
from Cancer Control: Journal of the Moffitt Cancer Center
Medscape (free login req.) 3_5_03
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Mini transplants - A good readable description
BMT
infoNet
This type of transplant relies on graft vs disease and uses lower doses
of chemo than other transplant regimes.
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Non-Myeloablative Transplantation (Posted Nov_28_02)
David G. Maloney, Brenda M. Sandmaier, Stephen
Mackinnon and Judith A. Shizuru
asheducationbook.org
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Nonmyeloablative Allogeneic Stem-Cell Transplantation for Hematologic Malignancies:
A Systematic Review
from Cancer Control: Journal of the Moffitt Cancer Center - Posted 03/05/2003
Medscape
Benjamin Djulbegovic, MD, PhD, Jerome Seidenfeld, PhD, Claudia Bonnell, BSN, MLS,
Ambuj Kumar, MD, MPH
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Transplant May Help Incurable Lymphomas - Less Toxic Treatment Appears to Cure Some Patients
ACS 01_22_03
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Non-Myeloablative Transplantation (Posted Nov_28_02),
by
David G. Maloney, Brenda M. Sandmaier,
Stephen
Mackinnon and Judith A. Shizuru
asheducationbook.org
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Patient SCT Stories -
Cyberfamily
| What to take to Hospital
Cyberfamily
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Less toxic bone marrow transplant technique may have more powerful anti-cancer effect
Researchers induce "chimeric" immune system in lymphoma patients
harvard.edu
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Re-immunization
after SCT |
Research News:
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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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Allogeneic stem cell transplantation following
reduced-intensity conditioning (RIC) can induce durable clinical
and molecular remissions in relapsed lymphomas: pre-transplant
disease status and histotype heavily influence outcome
nature.com
Relapse risk differed significantly at 3 years between
follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)
(14 versus 46%, P=0.04). Molecular remission occurred in 94 and
40% (P=0.002) of patients with FL and CLL, respectively.
On multivariate analysis, OS was influenced by chemorefractory
disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and
acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and
effective salvage strategy in both indolent and aggressive NHL
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Reduced Intensity Conditioning Regimens
nature.com
Low transplant-related mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant
With a median follow-up of 358 days (450 in 29 survivors), the
1-year incidence of TRM was 24%, and the 1-year overall (OS) and
progression-free survival were 63% and 57%, respectively.
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Review article:
Reduced-intensity transplantation for lymphoma.
Curr
Treat Options Oncol. 2006 Jul;7(4):295-305. Review.
PMID:
16916490
transplant-related morbidity and mortality and
graft-versus-host disease remain major obstacles, and future
efforts should focus on minimizing risks and more clearly
identifying patient-specific and disease-specific predictors of
outcome. |
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Outcome report (2007):
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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Optimization of allogeneic
transplant conditioning: not the time for dogma
nature.com
H J Deeg1,2,
M B Maris1,2,
B L Scott1,2
and E H Warren1,2
"As patients age, their
biologic reserve declines, and the capacity to repair tissue and
organ damage decreases. At the same time, however, the probability
of developing malignancies increases (although recent research
suggests that the senescence of cells, which underlies the reduced
repair capacity, may provide protection against cancer).
Nevertheless, older patients are more likely to suffer from
comorbid conditions, which will affect the candidacy for
transplantation.5,
22,
23
Reduced-intensity regimens are better tolerated ..."
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Outcome
report (2006): Stem cell transplantation with
reduced-intensity conditioning regimens: a review of ten years
experience with new transplant concepts and new therapeutic agents
nature.com
Leukemia (2006)
20,
1661–1672. doi:10.1038/sj.leu.2404334; published online 27 July
2006
A J Barrett1
and B N Savani1
The realization in the 1990s
that allogeneic stem cell transplants (SCT) have a potentially
curative graft-versus-leukemia (GVL) effect in addition to the
antileukemic action of myeloablative conditioning regimens was a
major stimulus for the development of reduced-intensity
conditioning (RIC) regimens, aimed primarily at securing
engraftment to provide the GVL effect, while minimizing
regimen-related toxicity. It is now over 10 years since RIC
regimens were heralded as a new direction in the field of SCT.
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Non-Myeloablative Allogeneic
Hematopoietic Transplantation in Relapsed/Primary Refractory
Follicular Lymphoma. Session Type: Poster Session 522-II
ASH
2004
"non-myeloablative" means pretreatment (conditioning
phase of treatment) that has lower toxicity and does not ablate
(kill off) the myeloid cells in the marrow. Often called a
mini-transplant. "Allogeneic" means from a donor,
in this case an HLA-identical sibling.
"Hematopoietic" means the process of forming blood cells
from stem cells in the bone marrow. |
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Nonmyeloablative Allogeneic Hematopoietic
Transplantation [mini]: A Promising Salvage Therapy for Patients
With Non-Hodgkin's Lymphoma Whose Disease Has Failed a Prior
Autologous Transplantation.
J Clin Oncol. 2004 Jun 15;22(12):2419-23.
PMID:
15197204 |
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HLA-matched unrelated donor hematopoietic cell
transplantation after nonmyeloablative conditioning for patients
with hematologic malignancies. Blood. 2003 Sep 15;102(6):2021-30.
Epub 2003 Jun 05.
PMID:
12791654 |
More
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Tandem Transplants: Patients with mantle-cell
lymphoma relapsing after autologous stem cell transplantation may be
rescued by allogeneic transplantation. Bone Marrow Transplant. 2000
Sep;26(6):677-9. PMID: 11035375
PubMed
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Nonablative allogeneic hematopoietic transplantation
as adoptive immunotherapy for indolent lymphoma: low incidence of
toxicity, acute graft-versus-host disease, and treatment-related
mortality. Blood. 2001 Dec 15;98(13):3595-9. PubMed
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