A CONTINUACIÓN PRESENTAMOS UNA SELECCIÓN DE LOS ARTICULOS
PUBLICADOS EN LAS PRINCIPALES REVISTAS CIENTIFICAS DONDE SE ANUNCIAN
LOS DIVERSOS AVANCES Y APLICACIONES ACTUALES DE LAS CELULAS MADRE
Combination of high-dose chemotherapy with stem cell transplant
from the patients themselves shows good response in treatment of
1. Dunkel, IJ; "High-dose chemotherapy
with autologous stem cell rescue for malignant brain tumors"; Cancer
Invest. 18, 492-493; 2000.
"Patients with recurrent medulloblastoma
had a significant improvement in long-term survival (median: 34
months) as compared with historical reports; two patients with glioblastoma
survive beyond four years without progression."
2. Abrey, LE et al.; "High
dose chemotherapy with autologous stem cell rescue in adults with
malignant primary brain tumors"; J. Neurooncol. 44, 147-153; Sept.,
"Review of HDCT and stem cell transplant
for children with brain tumors. Studies demonstrating durable disease-free
survival for a proportion of patients with recurrent malignant gliomas
and medulloblastomas/PNET, as well as encouraging data in some of
those patients with newly diagnosed brain tumors."
3. Finlay, JL; "The role of high-dose
chemotherapy and stem cell rescue in the treatment of malignant
brain tumors: a reappraisal"; Pediatr. Transplant 3 Suppl. 1, 87-95;
A localized retinoblastoma of the left
eye in a 7-year-old girl, was treated by enucleation. She received
no additional therapy. Four months later, metastases of retinoblastoma
in the lymph nodes, bone and bone marrow were diagnosed. Relapse
chemotherapy consisting of three courses of vincristine, cyclophosphamide,
etoposide and carboplatin led to a second complete remission.
Subsequent high-dose chemotherapy with
thiotepa, etoposide and carboplatin and autologous stem cell transplantation
with CD34-selected stem cells were successful, with no adverse effects.
No radiotherapy was given and the girl remains in continuous second
remission with a follow-up of more than 4 years.
4. Hertzberg H et al.;
"Recurrent disseminated retinoblastoma in a 7-year-old girl treated
successfully by high-dose chemotherapy and CD34-selected autologous
peripheral blood stem cell transplantation"; Bone Marrow Transplant
27(6), 653-655; March 2001
Patients with metastatic retinoblastoma
have a poor prognosis with conventional treatments. This study used
intensive conventional chemotherapy, high-dose chemotherapy, with
autologous stem cell rescue, and radiation therapy. The treatment
strategy was effective for all four patients with metastatic retinoblatoma
that does not involve the central nervous system, surviving event
free from 46-80 months after diagnosis.
5. Dunkel IJ et al.; "Successful
treatment of metastatic retinoblastoma"; Cancer 89, 2117-2121; Nov
15 2000.Updated June 25, 2001 Cancer
Treatments with Adult Stem Cells David A. Prentice 2
Report studying whether patients benefit
more from autologous stem cell transplantation. "Some patients with
ovarian cancer seem to have good outcomes after autotransplantation".
6. Stiff PJ et al.; "High-dose
chemotherapy and autologous stem-cell transplantation for ovarian
cancer: An autologous blood and marrow transplant registry report";
Ann. Intern. Med. 133, 504-515; Oct. 3, 2000
"Developing data suggest that this approach
in both of these settings merit further evaluation for the treatment
of epithelial ovarian carcinoma." Used autologous, purified peripheral
blood stem cells
7. Schilder, RJ and Shea, TC;
"Multiple cycles of high-dose chemotherapy for ovarian cancer";
Semin. Oncol. 25, 349-355; June 1998
**Merkel cell carcinoma is a rare cutaneous
tumor with neuroendocrine differentiation; there is no standard
protocol for treatment of the metastatic disease. This study used
high-dose chemotherapy and autologous peripheral blood stem cell
transplantation to achieve complete remission that lasted for 6
8. Waldmann V et al.;
"Transient complete remission of metastasized merkel cell carcinoma
by high-dose polychemotherapy and autologous peripheral blood stem
cell transplantation"; Br. J. Dermatol. 143, 837-839; Oct 2000
**Patients with metastatic or locally
advanced, unresectable soft tissue sarcoma are seldom curable, with
5-year survival rates of less than 10%. Used high-dose chemotherapy
with autologous hematopoietic stem cell transplant; "a high survival
rate was observed in HDCT-treated patients who were in complete
remission after conventional chemotherapy."
9. Blay JY et al.; "High-dose
chemotherapy with autologous hematopoietic stem-cell transplantation
for advanced soft tissue sarcoma in adults"; J. Clin. Oncol. 18,
3643-3650; Nov 1 2000
"The prognosis of metastatic malignant
mesenchymal tumors (MMT) remains poor." Used high-dose chemotherapy
with bone marrow or peripheral blood stem cell transplant. "A response
exceeding 50% was observed in 6/18 patients (response rate 33%)."
10. Lafay-Cousin L et al.;
"High-dose thiotepa and hematopoietic stem cell transplantation
in pediatric malignant mesenchymal tumors: a phase II study"; Bone
Marrow Transplant 26, 627-632; Sept. 2000
High-dose chemotherapy followed by autologous
haematopoietic rescue is widely used in the treatment of patients
with paediatric malignancies. It is now well established as a major
component for the treatment of children with metastatic neuroblastoma
over the age of one at diagnosis. Its place for other tumours, such
as metastatic Ewing and rhabdomyosarcoma, needs to be better established."
11. Michon, J and Schleiermacher,
G. "Autologous haematopoietic stem cell transplantation for paediatric
solid tumors", Baillieres Best Practice Research in Clinical Haematology
12, 247-259, March-June, 1999..Updated June 25, 2001 Cancer Treatments
with Adult Stem Cells David A. Prentice 3
Used for malignant solid tumors. Overall
response rate 96%, complete clinical response rate 67%. Treatment
described as safe, feasible, and active.
12. Schilder, RJ et al.;
"Phase I trial of multiple cycles of high-dose chemotherapy supported
by autologous peripheral-blood stem cells"; J. Clin. Oncol. 17,
2198-2207; July 1999
"Thirty-seven (57%) of the 65 patients
are continuously disease-free. Three additional patients are disease-free
with subsequent surgery. High-dose chemotherapy was associated with
significant morbidity but no treatment-related mortality. High-dose
chemotherapy as initial salvage chemotherapy achieved impressive
long-term survival with acceptable toxicity in patients with relapsed
13. Bhatia S et al.; "High-dose
chemotherapy as initial salvage chemotherapy in patients with relapsed
testicular cancer"; J. Clin. Oncol. 18, 3346-3351; Oct. 19, 2000
"High-dose chemotherapy with the transplantation
of peripheral blood stem cells (PBSC) has been performed for the
treatment of advanced testicular cancer patients." "After mobilization
of peripheral blood stem cells with G-CSF alone, sufficient amounts
of MNC were obtained from testicular cancer patients who had undergone
chemotherapy several times."
14. Hanazawa, K et al.;
"Collection of peripheral blood stem cells with granulocyte-colony-stimulating
factor alone in testicular cancer patients"; Int. J. Urol. 7, 77-82;
UMBILICAL CORD BLOOD EFFECTIVE
AT TREATING ADULT BLOOD DISORDERS
A new report shows that umbilical cord
blood can provide effective treatment of various blood disorders
in adults. It had previously been assumed that there were too few
stem cells in cord blood to treat adults, and only children were
treated. The results of this study show that cord blood stem cells
can proliferate extensively and provide sufficient numbers of cells
for adult treatments.
15. Laughlin MJ et al.;
"Hematopoietic engraftment and survival in adult recipients of umbilical-cord
blood from unrelated donors", New England Journal of Medicine 344,
1815-1822; June 14, 2001
This retrospective study included 21
children with acute lymphoblastic leukaemia, 15 with acute myelogenous
leukaemia and one each with chronic myelogenous leukaemia, refractory
anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic
leukaemia (JMML). These data confirm that HLA-mismatched, unrelated
CBT is a feasible procedure to cure a significant proportion of
children with leukaemia, especially if conducted in a favourable
phase of the disease.
16. Ohnuma K et al.; "Cord
blood transplantation from HLA-mismatched unrelated donors as a
treatment for children with haematological malignancies"; Br J Haematol
112(4), 981-987; March 2001.Updated June 25, 2001 David A. Prentice
a lymphoproliferative disorder with
abnormalities characteristic of malignant T cell lymphoma (angioimmunoblastic
T cell lymphoma -- -year old male patient with unusually aggressive
AILD, At relapse, treatment with high dose chemotherapy shown to
be successful. The patient is alive and disease-after APSCT. Considering
the poor prognosis of the majority of patients with AILD, intensive
17. Lindahl J ; "High-hemolysing
AILD"; Leuk Res 25(3), 267- 1 Patients given high-blood stem cells
rather than bone marrow results in higher rates of overall and disease-and
restores blood counts faster. Patients in whom the benefit of peripheral
blood cells was most apparent were those with advanced hematologic
cancer. Other studies have also shown that the use -blood cells
is associated with fewer days of hospitalization and lower overall
. Bensinger WI ; "Transplantation
of bone marrow as compared with peripheral-from HLA-Medicine
344, 175-ng stem cell transplantation.
The authors note that "Stem cell transplantation has been successfully
used to treat a wide variety of hematologic malignancies. Newul
inovercoming tumor resistance."
Margolis J et al.Semin. Oncol.
27, 524-apeutic approach in patients with acute myelocytic leukemia
over 60 years of age."
Gorin NC et al. acut myelocytic
leukaemia in patients over 60 years of age: importance of the source
of stem -893; Sept 2000
"Infants with acute leukemia have a
poor prognosis when treated with conventional chemotherapy." -year
overall survival 64%. "SCT is a valid option in the treatment of
inf may overcome the high risk of relapse with conventional chemotherapy
showing very reduced toxicity."
Marco F et al. -Dose -C -3261;
Sept. 15 2000.Updated June 25, 2001 Cancer Treatments with Adult
Stem Cells David A. Prentice 5
"Actuarial survival and disease-free
survival at 34 months are 56% and 50% respectively, with 95% confidence
interval (25-78%).These results suggest that nonmyeloablative conditioning
significantly reduces transplant-related toxicity, thus making a
second transplant feasible."
22. Nagler A et al.; "Second
allogeneic stem cell transplantation using nonmyeloablative conditioning
for patients who relapsed or developed secondary malignancies following
autologous transplantation"; Exp. Hematol. 28, 1096-1104, Sept.
Review of autologous stem cell treatment
strategies. "Controlled clinical trials have demonstrated a long-term
disease-free survival of 40%-50% for patients treated with at least
two courses of HIDAC.
Other studies have demonstrated that
postremission autologous bone marrow transplantation results in
a disease-free survival equal to or better than conventional chemotherapy.
However, autotransplantation with mobilized peripheral blood stem
cells (PBSC) would now be preferred instead of autologous bone marrow,
due to the shorter hematopoietic reconstitution period."
23. Bruserud O et al.;
"New strategies in the treatment of acute myelogenous leukemia:
mobilization and transplantation of autologous peripheral blood
stem cells in adult patients"; Stem Cells 18, 343-351; 2000
Study to evaluate high-dose melphalan
followed by autologous stem-cell transplantation in patients with
refractory multiple myeloma. High-dose therapy with melphalan 200
mg/m(2) is feasible with high response rates (58% overall) and an
OS of 19 months in patients with refractory multiple myeloma."
24. Vesole, DH et al.;
"High-Dose Melphalan With Autotransplantation for Refractory Multiple
Myeloma: Results of a Southwest Oncology Group Phase II Trial";
J Clin Oncol 17, 2173-2179; July 1999.
**The "data suggest that high-dose chemotherapy
with hematopoietic stem cell rescue is safe and can be beneficial
to patients with high-risk primary breast cancer and for those with
metastatic breast cancer achieving complete response/no evidence
25. Damon LE et al.; "High-dose
chemotherapy and hematopoietic stem cell rescue for breast cancer:
experience in California"; Biol. Blood
Marrow Transplant 6, 496-505; 2000 Stem cells in circulating blood
can be isolated, expanded in number in culture, and provide better
26. Paquette, RL et al.,
"Ex vivo expanded unselected peripheral blood: progenitor cells
reduce posttransplantation neutropenia, thrombocytopenia, and anemia
in patients with breast cancer", Blood 96, 2385-2390; October, 2000..Updated
June 25, 2001 Cancer Treatments with Adult Stem Cells David A. Prentice
"The collection of small aliquots of
bone marrow (BM), followed by ex vivo expansion for autologous transplantation
may be less morbid, and more cost-effective, than typical BM or
blood stem cell harvesting. Passive elimination of contaminating
tumor cells during expansion could reduce reinoculation risks."
"It is feasible to perform autotransplants solely with BM cells
grown ex vivo in perfusion bioreactors from a small aliquot." this
procedure could reduce the risk of tumor cell reinoculation with
autotransplants and may be valuable in settings in which small stem
cell doses are available, eg, cord blood transplants."
27. Stiff P et al.; "Autologous
transplantation of ex vivo expanded bone marrow cells grown from
small aliquots after high-dose chemotherapy for breast cancer";
Blood 95, 2169-2174; March 15, 2000
"This report is the first describing
infusion of autologous MSCs with therapeutic intent. We found that
autologous MSC infusion at the time of PBPC transplantation is feasible
and safe. The observed rapid hematopoietic recovery suggests that
MSC infusion after myeloablative therapy may have a positive impact
on hematopoiesis and should be tested in randomized trials."
28. Koc, ON et al.; "Rapid
Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem
Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced
Breast Cancer Patients Receiving High-Dose Chemotherapy"; J Clin
Oncol 18, 307-316; January 2000
"According to initial reports, stage
4 neuroblastoma patients with amplification of the MYCN proto-oncogene
developed progressive disease within 8 months. The prognosis for
such patients, however, should now be reevaluated in light of recent
results achieved with up-to-date combination chemotherapy. Not all
patients with advanced neuroblastoma who have more than 10 copies
of MYCN will die. The requisites for survival in such patients seem
to be intensive induction chemotherapy, effective surgery, irradiation,
and the use of SCT" (stem cell transplant).
29. Kawa, K et al.; "Long-Term
Survivors of Advanced Neuroblastoma With MYCN Amplification: A Report
of 19 Patients Surviving Disease-Free for More Than 66 Months";
J Clin Oncol 17:3216-3220; October 1999
"To determine differences in prognosis
between primary progressive Hodgkin's disease (HD) and aggressive
non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients
with progressive lymphoma who were treated with different salvage
chemotherapy regimens including high-dose chemotherapy (HDCT) followed
by autologous stem-cell support (ASCT). There are striking differences
in the prognosis of patients with progressive HD and aggressive
NHL. The prognosis of progressive NHL patients is dismal. Most patients
have rapidly progressive disease after salvage treatment and are,
therefore, excluded from HDCT programs. In contrast, progressive
HD patients can achieve long-term survival after HDCT."
30. Josting, A; "Treatment of
Primary Progressive Hodgkins and Aggressive Non-Hodgkins
Lymphoma: Is There a Chance for Cure?"; J Clin Oncol 18, 332-339;
"Patient achieved complete remission
and has survived in continuous complete remission for more than
72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT
is thought to be useful as part of the primary therapy for patients
with NHL who have poorer prognoses."
Reference:.Updated June 25, 2001
Cancer Treatments with Adult Stem Cells David A. Prentice7
31. Kirita T et al.; "Primary
non-Hodgkins lymphoma of the mandible treated with radiotherapy,
chemotherapy, and autologous peripheral blood stem cell transplantation";
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 90, 450-455; Oct.
"These results suggest first that ex
vivo expansion of hematopoietic stem cells in patients with non-Hodgkin's
lymphoma is feasible without incurring the parallel risk of amplifying
tumor cells; second, that Flt3-L did not stimulate the growth of
tumor cells while it clearly favored the growth of normal progenitors."
32. Yao M et al.; "Ex
vivo expansion of CD34-positive peripheral blood progenitor cells
from patients with non-Hodgkins lymphoma: no evidence of concomitant
expansion of contaminating bcl2/JH-positive lymphoma cells"; Bone
Marrow Transplant 26, 497-503; Sept. 2000
RENAL CELL CARCINOMA
"Nonmyeloablative allogeneic stem-cell
transplantation can induce sustained regression of metastatic renal-cell
carcinoma in patients who have had no response to conventional immunotherapy."
33. Childs R et al., "Regression
of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic
Peripheral-Blood Stem-Cell Transplantation", New England Journal
of Medicine 343, 750-758; Sept. 14, 2000
"The complete regression of metastatic
disease, which has now been maintained for more than 1 year, is
compatible with a graft-versus-tumor effect."
34. Childs, RW; "Successful Treatment
of Metastatic Renal Cell Carcinoma With a Nonmyeloablative Allogeneic
Peripheral-Blood Progenitor-Cell Transplant: Evidence for a Graft-Versus-Tumor
Effect:; J Clin Oncol 17, 2044-2049; July 1999.Updated June 25,
2001 Autoimmune Disease Treatments with Adult Stem Cells David A.
multiple sclerosis, systemic lupus erythematosus, juvenile rheumatoid
arthritis, rheumatoid arthritis
High-dose chemotherapy followed by autologous
HSCT is feasible and safe, and can result in long-term improvement
of disease activity in patients whose condition previously did not
respond to conventional antirheumatic drugs or TNF blocking agents.
The persistence of active disease in some patients may reflect the
heterogeneity of the underlying disease process.
35. Verburg RJ et al.;
"High-dose chemotherapy and autologous hematopoietic stem cell transplantation
in patients with rheumatoid arthritis: results of an open study
to assess feasibility, safety, and efficacy"; Arthritis Rheum 44(4),
754-760; April 2001
36. Wulffraat NM et al.;
"Prolonged remission without treatment after autologous stem cell
transplantation for refractory childhood systemic lupus erythematosus";
Arthritis Rheum 44(3), 728-731; March 2001
** "Autoimmune diseases that are resistant
to conventional treatment cause severe morbidity and even mortality.
In the present study we demonstrate that complete remissions can
be achieved in refractory polychondritis and systemic lupus erythematosus
(SLE), even at advanced stage, with the use of autologous stem-cell
transplantation (SCT). Remissions persisted after reconstitution
of the immune system. In the treatment of advanced systemic sclerosis
(SSc), stable disease may be achieved with autologous SCT."
37. Rosen O et al.; "Autologous
stem-cell transplantation in refractory autoimmune diseases after
in vivo immunoablation and ex vivo depletion of mononuclear cells";
Arthritis res. 2, 327-336; 2000
Nineteen patients (14 female, 5 male)
with severe autoimmune diseases were treated. Nine had a rheumatologic
disorder (5 juvenile chronic arthritis, 1 rheumatoid arthritis,
1 systemic vasculitis, 1 Sjogren's syndrome, 1 Behct's disease),
4 a neurologic disorder (3 multiple sclerosis, 1 myasthenia), 3
a haematologic disease (2 pure red cell aplasia, 1 autoimmune thrombocytopenia),
2 had a gastrointestinal disease (1 Crohn's disease, 1 autoimmune
enteropathy) and 1 had a multiple autoimmune disorder. There was
no regimen-related toxicity and no opportunistic infections occurred.
Ninety percent of the patients improved and/or had a complete remission
after the procedure. Fifty percent of the subjects went into complete
or partial remission after a median follow-up of 15 months. A non-myeloablative
conditioning regimen was able to induce persistent remission in
some patients with severe autoimmune diseases. There was no mortality
or morbidity related to the procedure. The extent of remission remains
to be established.
38. Rabusin M et al.;
"Immunoablation followed by autologous hematopoietic stem cell infusion
for the treatment of severe autoimmune disease"; Haematologica 85(11
Suppl), 81-85; Nov. 2000.Updated June 25, 2001 Autoimmune Disease
Treatments with Adult Stem Cells David A. Prentice 9
**Study that supports the concept that
patients with autoimmune cytopenias with severe resistant disease
might be appropriate candidates for autologous stem cell transplantation.
39. Papadaki HA et al.;
"Assessment of bone marrow stem cell reserve and function and stromal
cell function in patients with autoimmune cytopenias"; Blood 96,
3272-3275; Nov 1 2000
Patients (including several children)
with severe lupus were treated with their own bone marrow stemcells,
and had relief of symptoms, with little or no need for medication
40. Traynor AE et al.;
"Treatment of severe systemic lupus erythematosus with high-dose
chemotherapy and haemopoietic stem-cell transplantation: a phase
I study"; Lancet 356, 701-707; August 26, 2000
Numerous studies showing efficacy of
adult stem cell transplants in the successful treatment of autoimmune
41. Burt, RK and Traynor, AE;
"Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune
Disease"; Stem Cells17, 366-372; 1999
Overviewjuvenile rheumatoid arthritis;
multiple sclerosis; rheumatoid arthritis; systemic lupus erythematosus.
42. Burt RK et al.; "Hematopoietic
stem cell transplantation of multiple sclerosis, rheumatoid arthritis,
and systemic lupus erythematosus"; Cancer Treat. Res. 101, 157-184;
43. Traynor A and Burt RK; "Haematopoietic
stem cell transplantation for active systemic lupus erythematosus";
Rheumatology 38, 767-772; August 1999
44. Martini A et al.;
"Marked and sustained improvement 2 years after autologous stem
cell transplant in a girl with system sclerosis"; Rheumatology 38,
773; August 1999
45. Hawkey CJ et al.;
"Stem cell transplantation for inflammatory bowel disease: practical
and ethical issues"; Gut 46, 869-872; June 2000
46. Burt, RK et al., "Autologous
hematopoietic stem cell transplantation in refractory rheumatoid
arthritis: sustained response in two of four patients", Arthritis
& Rheumatology 42, 2281-2285,
47. Burt, R.K. et al.,
"Gene-marked autologous hematopoietic stem cell transplantation
autoimmune disease", Journal of Clinical
Immunology 20, 1-9; January 2000..Updated June 25, 2001 Other Clinical
Uses of Adult Stem Cells David A. Prentice 10
A cultured stem cell line (originally
derived from an adult tumor; a "teratocarcinoma", sometimes called
an "embryonal carcinoma" because it mimics some of the characteristics
of embryonic cells.)
The cultured and adapted cell line was
used in successful treatment of several stroke patients.
48. Kondziolka D et al.;
"Transplantation of cultured human neuronal cells for patients with
stroke"; Neurology 55, 565-569; August 2000
Banked unrelated umbilical cord blood
was used to reconstitute the immune system in 2 brothers with X-linked
lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M
syndrome. Two years after transplantation, all 3 patients have normal
immune systems. These reports support the wider use of banked partially
matched cord blood for transplantation in primary immunodeficiencies.
49. Ziegner UH et al.;
"Unrelated umbilical cord stem cell transplantation for X-linked
immunodeficiencies"; J Pediatr 138(4), 570-573; April 2001
Eight children with severe immunodeficiencies
treated by adult bone marrow stem cell transplants.
Six of 8 showed relatively normal immune
systems after 1 year.
50. Amrolia, P. et al.,
"Nonmyeloablative stem cell transplantation for congenital immunodeficiencies",
Blood 96, 1239-1246, Aug. 15, 2000.
Allogeneic peripheral blood stem cell
transplantation (PBSCT) is rarely applied for the treatment of severe
aplastic anemia (SAA) because of questionable durability of engraftment
and increased risk of graft versus host disease (GVHD). We performed
allogeneic PBSCT in 3 SAA patients from their human leukocyte antigen
(HLA)-identical siblings. In 2 cases, no graft failure has been
observed, and a successful and complete hematological recovery was
achieved and maintained for 28 and 25 months, respectively. In conclusion,
PBSCT provides a quick and complete hematological recovery in SAA
51. Gurman G et al.; "Allogeneic
peripheral blood stem cell transplantation for severe aplastic anemia";
Ther Apher 5(1), 54-57; Feb. 2001
Results suggest that treatment can reverse
progression of vasculopathy. Bone marrow transplantation may enable
stenoses to heal and can substantially reduce cranial blood velocity,
suggesting that allogeneic bone marrow transplantation may prevent
infarction or brain damage.
52. Steen RG et al.; "Improved
cerebrovascular patency following therapy in patients with sickle
cell disease: initial results in 4 patients who received HLA-identical
hematopoietic stem cell allografts"; Ann Neurol 49(2), 222-229;
Feb. 2001.Updated June 25, 2001 Other Clinical Uses of Adult Stem
Cells David A. Prentice 11
Able to treat severe anemias using transplants
of adult bone marrow stem cells.
53. Gonzalez MI et al.;
"Allogeneic peripheral stem cell transplantation in a case of hereditary
sideroblastic anaemia"; British Journal of Haematology 109, 658-660;
54. Kook H et al.; "Rubella-associated
aplastic anemia treated by syngeneic stem cell transplantations";
Am. J. Hematol. 64, 303-305; August 2000
Possibility of using adult stem cell
transplantation as cure for sickle cell anemia.
55. Wethers DL; "Sickle cell
disease in childhood: Part II. Diagnosis and treatment of major
complications and recent advances in treatment"; Am. Fam. Physician
62, 1309-1314; Sept. 15, 2000
Successful treatment of a congenital
thrombocytopenia using allogeneic peripheral blood stem cell transplantation.
56. Yesilipek et al.;
"Peripheral stem cell transplantation in a child with amegakaryocytic
thrombocytopenia"; Bone Marrow Transplant 26, 571-572; Sept. 2000
Chronic Viral Infection With Complications
57. Fujii N et al.; "Allogeneic
peripheral blood stem cell transplantation for the treatment of
chronic active epstein-barr virus infection"; Bone Marrow Transplant
26, 805-808; Oct. 2000
58. Okamura T et al.;
"Blood stem-cell transplantation for chronic active Epstein-Barr
virus with lymphoproliferation"; Lancet 356, 223-224; July 2000
and Bone Diseases>
59. Biopsies removed from 57
patients considered for cartilage transplantation were grown. Explant
cultures allowed cell number expansion. Fifty-four out of 57 biopsies
grew cells. Fanning out of the cells began after 5-15 days in culture.
Two passages later, cell numbers in the 10(7) range were achieved.
Explants of articular chondrocytes cultured in vitro consistently
yield monolayer cultures. The cells appear to revert to dedifferentiated
chondrocytes, expressing a mesenchymal stem cell protein profile.
Simultaneously, these cells regained their capacity to proliferate.
60. Robinson D et al.;
"Characteristics of cartilage biopsies used for autologous chondrocytes
transplantation"; Cell Transplant 10(2), 203-208; 2001 Mar-Apr
61. Horwitz, EM et al.;
"Transplantability and therapeutic effects of bone marrow-derived
mesenchymal cells in children with osteogenesis imperfecta"; Nat.
Med. 5, 309-313; March 1999..Updated June 25, 2001 Other Clinical
Uses of Adult Stem Cells David A. Prentice 12
Fifteen of 16 eyes (93.7%) achieved
epithelialization with a mean time to epithelial healing of 15.2
days. The only eye that failed to heal was subsequently diagnosed
with total limbal stem cell deficiency. Visual acuity improved in
five of nine (44%) sighted eyes. No patient experienced any major
surgical or medical complication after the procedure. Amniotic membrane
transplantation represents a safe and effective method to restore
a stable corneal epithelium in eyes after primary surgical removal
of band keratopathy arising from ocular causes.
62. Adnerson DF et al.;
"Amniotic Membrane Transplantation After the Primary Surgical Management
of Band Keratopathy"; Cornea 20(4), 354-361; May 2001
Amniotic membrane transplantation appears
to be a safe and effective method of restoring a stable corneal
epithelium for cases of partial limbal stem cell deficiency and
can be considered as an alternative to limbal autograft or allograft.
17 eyes of 15 patients; All eyes exhibited a stable, intact corneal
epithelial surface after a mean follow up period of 25.8 months
with no eyes developing recurrent erosion or persistent epithelial
defect. The mean time to re-epithelialisation was 22.8 days.
Overall improvement in visual acuity
was observed in 92.9% of 14 eyes with visual potential.
63. Anderson DF et al.;
"Amniotic membrane transplantation for partial limbal stem cell
deficiency"; Br J Ophthalmol 85(5), 567-575; May 2001
An objective long term benefit from
the procedure (improved Snellen acuity, reduced frequency of epithelial
defects, reduced vascularisation, and scarring) was recorded for
four out of five patients.
Some subjective benefit was also reported.
However, in no instances were donor cells recovered from the ocular
surface at 3-5 years post-graft. Initial experiments to examine
sensitivity indicated that any surviving donor cells must have constituted
less than 2.5% of cells sampled. Limbal stem cell allotransplantation
can provide long term benefits, as measured by objective criteria.
However, such benefits do not necessarily correlate with survival
of measurable numbers of donor cells on the ocular surface.
64. Henderson TR et al.;
"The long term outcome of limbal allografts: the search for surviving
cells"; Br J Ophthalmol 85(5), 604-609; May 2001
**Adult stem cells from relatives used
to restore vision Nine living related donors, 8 recipients (10 eyes,
various conditions). Restoration of corneal epithelium, opacification
reduced, visual improvement; 2 initial failures.
65. Daya SM, Ilari FA; "Living
related conjuctival limbal allograft for the treatment of stem cell
deficiency"; Opthalmology 180, 126-133;
January 2001.Updated June 25, 2001 Other Clinical Uses of Adult
Stem Cells David A. Prentice13
Adult Stem Cells Used to Grow New Corneas
Researchers in the United States and Taiwan have used corneal adult
stem cells to grow new corneas for patients with previously untreatable
eye damage. Adult stem cells were taken from the patients themselves
in 16 cases, or a family member for 4 other patients. The cells
were then grown in culture before transplantation onto the damaged
eyes. Sixteen of the 20 patients had improved vision. Dr. Ivan Schwab,
professor of ophthalmology at the University of California at Davis
Medical School,leader of the U.S. team, said "We think this is the
beginning of a very exciting change in terms of how we manage surface
disease of many kinds, not just in the eye."
66. Schwab IR et al.;
"Successful transplantation of bioengineered tissue replacements
in patients with ocular surface disease"; Cornea 19, 421-426; July
67. Tsai et al.; "Reconstruction
of damaged corneas by transplantation of autologous limbal epithelial
cells."; New England Journal of Medicine 343, 86-93, 2000.
68. Tsubota K et al.;
"Treatment of severe ocular-surface disorders with corneal epithelial
stem-celltransplantation"; New England Journal of Medicine 340,
1697-1703; June 3, 1999
and Liver Disease>
**4-month-old girl received stem cell
transplant after receiving living-related liver transplant from
same donor (mother). Four months after stem cell transplant the
patient was disease-free, complete donor chimerism in bone marrow
and stable hepatic function without any immunosuppressive therapy.
69. Matthes-Martin S et al.;
"Successful stem cell transplantation following orthotopic liver
transplantation from the same haploidentical family donor in a girl
with hemophagocytic lymphohistiocytosis"; Blood 96, 3997-3999; Dec
**Primary amyloidosis is a plasma cell
disorder in which deposits of amyloid protein cause progressive
organ failure; most common target is the kidney, although heart,
liver, and nervous tissue effects are also seen. Compared to standard
treatments, high-dose chemotherapy with autologous peripheral blood
stem cell transplantation is shown to be much more effective in
the clinical condition of patients.
70. Sezer O et al.; "Novel
approaches to the treatment of primary amyloidosis"; Exper Opin.
Investig. Drugs 9, 2343-2350; Oct 2000
*First successful trial of human therapy,
re-injecting the infants own bone marrow stem cells containing
a normal copy of the gene that they lacked.
71. Cavazzana-Calvo M et al.;
"Gene therapy of human severe combined immunodeficiency (SCID)-X1
disease"; Science 288, 669-672; April 28, 2000.Updated June 25,
2001 Other Clinical Uses of Adult Stem Cells David A. Prentice 14
First successful human stem cell
treatment for heart disease uses adult stem cells
The first reports of successful treatment
for heart disease using the patients own adult muscle stem
cells are encouraging news regarding therapy after heart attack.
French physicians implanted skeletal muscle stem cells back into
the patient; the encouraging result after eight months follow-up
underlines the potential of this new approach using adult stem cells.
Further clinical trials are now underway in Europe and the U.S.
for other patients with heart disease. No embryonic stem cells have
ever been reported to be used in human trials.
A review of potential heart treatments
notes that cell transplantation is a potential therapeutic approach
for patients with chronic heart failure. Experimental transplantation
of muscle cells showed that the grafted cells can functionally integrate
with and augment the function of the recipient heart.
The scientists note that skeletal stem
cells are abundant and can be grafted successfully into the animals
own heart even after genetic manipulation in vitro.
72. Menasché P et al.
"Myoblast transplantation for heart failure." Lancet 357,
279-280; Jan 27, 2001
73. Menasché P et al.
["Autologous skeletal myoblast transplantation for cardiac insufficiency.
First clinical case."] [article in French] Arch Mal Coeur Vaiss
94(3), 180-182; March 2001
74. "Doctor Puts Arm Muscle Cells
Into Patient's Heart", Associated Press, May 30, 2001
75. "First Percutaneous Endovascular
Case of Heart Muscle Regeneration Completed with Bioheart's MyoCell(TM)
Product", PRNewswire, May 30, 2001.
76. El Oakley RM et al.;
"Myocyte transplantation for cardiac repair: A few good cells can
mend abroken heart"; Annals of Thoracic Surgery 71, 1724
1733; 2001.Updated June 25, 2001 Other Clinical Uses of Adult
Stem Cells David A. Prentice15
References Related to Clinical Uses of Adult Stem
Recent studies have revealed that much
of this remarkable developmental potential of embryonic stem cells
is retained by small populations of cells within most tissues in
the adult. Intercellular signals that control the proliferation,
differentiation and survival of stem cells are being identified
and include a diverse array of growth factors, cytokines and cell
adhesion molecules. Intracellular mechanisms that regulate stem
cell fate are also emerging and include established second messenger
pathways, novel transcription factors and telomerase. The possibility
that a decline in the numbers or plasticity of stem cell populations
contributes to aging and age-related disease is suggested by recent
The remarkable plasticity of stem cells
suggests that endogenous or transplanted stem cells can be 'tweaked'
in ways that will allow them to replace lost or dysfunctional cell
populations in diseases ranging from neurodegenerative and hematopoietic
disorders to diabetes and cardiovascular disease.
77. Rao MS and Mattson MP; "Stem
cells and aging: expanding the possibilities"; Mech Ageing Dev 122(7),
713-734; May 31, 2001
Mesenchymal stem cells (MSCs) are the
first non-hematopoietic progenitors to be isolated from the bone
marrow and extensively characterized. In addition to their ability
to support hematopoiesis, MSCs can differentiate into osteocytes,
chondrocytes, tenocytes, adipocytes and smooth muscle cells. This
article will review our current understanding of bone marrow stroma
and MSCs and their potential therapeutic role in the setting of
hematopoietic stem cell transplantation.
78. Koc ON and Lazarus HM; "Mesenchymal
stem cells: heading into the clinic"; Bone Marrow Transplant 27(3),
235-239; Feb. 2001 It appears that basal haematopoiesis is maintained
throughout life, yet, the capacity to cope with haematological stress
is decreased in advanced age. In principle, stem cells derived from
aged donors can be used for autologous transplantation, when needed
to recover basic haematopoiesis. Current methods for expansion and
maintenance of stem cells in vitro enable examination of stem cell
potential for long-term expansion and function. Understanding of
the mechanisms underlying these processes will enable the fidelity
of stem cell expansion and maintenance of their potential for long-term
79. Globerson A; "Haematopoietic
stem cell ageing"; Novartis Found Symp 235, 85-96; discussion 96-100,
This study examined whether cryopreservation
following expansion has a detrimental effect on the ability of cells
to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34(+)
cells were incubated for 7 days with stem cell factor (SCF), flt-3
ligand (FL), and megakaryocyte growth and development factor (MGDF).
Expanded CD34(+) cells were transplanted into NOD-SCID mice either
fresh or following cryopreservation
and thawing. Thawed expanded CD34(+)
cells had significantly higher SCID Engrafting.Updated June 25,
2001 Other Clinical Uses of Adult Stem Cells David A. Prentice 16
Potential (SEP) than freshly expanded
CD34(+) cells. Results suggest that priorcryopreservation does not
prevent expanded cells engrafting in NOD-SCID mice.
80. Rice AM et al.; "Prior
cryopreservation of ex vivo-expanded cord blood cells is notdetrimental
to engraftment as measured in the nod-scid mouse model"; J Hematother
Stem Cell Res 0(1), 157-165; Feb. 2001.Updated June 25, 2001 Other
Clinical Uses of Adult Stem Cells David A. Prentice 17
Represents the first case of successful
transplantation of PBSC, cryopreserved twice and purged after cryopreservation.
Indicates that purging procedures can successfully be carried out
with cryopreserved cell material and that purified CD34+ cells can
be cryopreserved a second time before transplantation, without affecting
their hematopoietic capacity.
81. Humpe A et al.; "Successful
transplantation and engraftment of peripheral blood stem cells after
cryopreservation, positive and negative purging procedures, and
a second cryopreservation cycle"; Ann Hematol 80(2), 109-112; Feb.
General review of growth factors using
in hematopoietic stem cell transplants. Recently, EPO has been shown
to significantly accelerate hematopoietic reconstitution after peripheral
blood stem cell transplantation (PBSCT) resulting in reduced infection
Both, G-CSF and GM-CSF have been shown,
in numerous trials, to shorten the period of chemotherapy-induced
neutropenia, with reduction in attendant morbidity and to mobilize
PBSC. In addition, administration of both cytokines after PBSCT
significantly reduced the use of antibiotics and duration of hospitalization
suggesting an economic benefit.
82. Dempke W et al.; "Human
hematopoietic growth factors: old lessons and new perspectives";
Anticancer Res 20(6D), 5155-5164; 2000 Nov-Dec Review of increasing
use of umbilical cord blood for transplants; banking of cells, etc.
83. Surbek DV and Holzgreve W;
"Fetal cells from cord blood as stem cell source: current status
and possible implications in gynaecologic oncology"; Eur J Gynaecol
Oncol 22(1), 6-12; 2001
Mobilized peripheral blood progenitor
cells (PBSC) are increasingly being used instead of bone marrow
for allogeneic transplantation. This article gives a concise and
clinically oriented overview on current results and perspectives
of allogeneic peripheral blood stem cell transplantation, with particular
focus on reconstitution of hematopoiesis and the immune system,
graft-versus-host disease, graft-versus-leukemia effects, intensity-reduced
conditioning, and graft engineering.
84. Dreger P and Schmitz N; "Allogeneic
transplantation of blood stem cells: coming of age?"; Ann Hematol
80(3), 127-136; March 2001
**Previously reported human stem cell
frequencies and their in vivo self-renewal activity have been markedly
85. Cashman JD and Eaves CJ;
"High marrow seeding efficiency of human lymphomyeloid repopulating
cells in irradiated NOD/SCID mice"; Blood 96, 3979-3981; Dec. 1
2000.Updated June 25, 2001 Other Clinical Uses of Adult Stem Cells
David A. Prentice 18
**Evidence for expansion protocol to
maintain cord blood stem cells for clinical applications.
86. Kobari L et al.; "In
vitro and in vivo evidence for the long-term multilineage (myeloid,
B, NK, and T) reconstitution capacity of ex vivo expanded human
CD34(+) cord blood cells"; Exp Hematol 28, 1470-1480, December 2000.Updated
June 25, 2001 Other Clinical Uses of Adult Stem Cells David A. Prentice
**Study notes that disease recurrence
is lower after peripheral blood stem cell transplants than with
bone marrow; "The general opinion is that peripheral blood grafts
are indicated for patients with advanced disease, whereas for patients
with early-phase disease the two sources may give comparable results."
87. Bacigalupo A et al.;
"Bone marrow or peripheral blood as a source of stem cells for allogeneic
transplants"; Curr. Opin. Hematol. 7, 343-347; Nov 2000
**Quality of life for 415 adult patients
who received hematopoietic stem cell transplants was measured; typical
patients can look forward to a quality of life after transplantation
that is broadly comparable to that of the normal population.
88. Bush NE et al.; "Conditional
and unconditional estimation of multidimensional quality of life
after hematopoietic stem cell transplantation: a longitudinal follow-up
of 415 patients"; Biol. Blood Marrow Transplant 6, 576-591; 2000
**Review of techniques to mobilize hematopoietic
bone marrow stem cells into peripheral blood.
89. Fu S, Liesveld J; "Mobilization
of hematopoietic stem cells"; Blood Rev 14, 205-218;
**Technique to expand numbers of human
hematopoietic stem cells in culture. Cells from umbilical cord blood
and adult patient peripheral blood were expanded with 2 factors,
flt-3 ligand and thrombopoietin/c-mpl ligand, and maintained for
prolonged periods (up to 16 weeks), and sufficient numbers were
generated for adult transplantation.
90. Gilmore GL et al.;
"Ex vivo expansion of human umbilical cord blood and peripheral
blood CD34(+) hematopoietic stem cells";
Exp. Hematol. 28, 1297-1305; Nov 1 2000
**Review of records for cord blood stem
cell transplants. Results showed survival comparable to bone marrow
transplants. "This large registry study confirms the potential benefit
of using umbilical cord blood hematopoietic stem cells for allogeneic
91. Gluckman E; "Current status
of umbilical cord blood hematopoietic stem cell transplantation";
Exp. Hematol. 28, 1197-1205; Nov 1 2000
Review of potentials for stem cell transplantation.
92. Steward CG; "Stem cell transplantation
for non-malignant disorders"; Baillieres Best Pract. Res. Clin.
Haematol. 13, 343-363; Sept. 2000
93. Slavin S; "new strategies
for bone marrow transplantation"; Curr. Opin. Immunol. 12,
542-551; Oct. 2000.Updated June 25,
2001 Other Clinical Uses of Adult Stem Cells David A. Prentice 20
Improved technique to quickly expand
numbers of cord blood cells in culture, allowing adequate numbers
for treatment of adult patients.
94. McNiece I et al.;
"Increased expansion and differentiation of cord blood products
using a two-step expansion culture";
Exp. Hematol. 28, 1181-1186; Oct. 2000.Updated June 25, 2001 Other
Clinical Uses of Adult Stem Cells David A. Prentice 21
"Can expand primitive hematopoietic
progenitors from Cord Blood and Peripheral Blood and expanded cells
retain the capacity for myeloid and lymphoid differentiation. These
findings emphasize the importance of assessing multi-lineage differentiation
capacity following ex-vivo expansion.
95. Lewis ID, Verfaillie CM;
"Multi-lineage expansion potential of primitive hematopoietic progenitors.
Superiority of umbilical cord blood compared to mobilized peripheral
blood"; Exp. Hematol. 28, 1087-1095; Sept. 1, 2000
Generating a high frequency of clonally
repopulating stem cells from blood.
96. Cho RH, Muller-Sieburg CE;
"High frequency of long-term culture-initiating cells retain in
vivo repopulation and self-renewal capacity"; Exp. Hematol. 28,
1080-1086; Sept. 1, 2000
97. Jacobs P et al.; "Allogeneic
stem cell transplantation. An economic comparison of bone marrow,
peripheral blood, and cord blood technologies"; Int. J. Technol.
Assess Health Care 16, 874-884; Summer
Autologous (same patient) circulating
blood stem cell transplants show faster recovery, less transplant
problems, shorter hospital stay, and reduced cost compared to bone
98. "Overview of autologous stem
cell transplantation", Saba, N et al., Critical Reviews of
Oncology and Hematology 36, 27-48, October 2000.
Allogeneic peripheral blood stem cell
transplants as good or better than bone marrow
99. Ringden O et al.,
"Peripheral blood stem cell transplantation from unrelated donors:
a comparison with marrow transplantation", Blood 94, 455; July 15,
Reviews of current protocols allowing
better methods for collection of stem cells from peripheral blood.
100. Hester J; "Peripheral blood
stem cell collection: the interaction of technology, procedure,
and biological factors"; Transfus. Sci. 23, 125-132; Oct. 2000
101. Kessinger A; "Collection
of autologous peripheral blood stem cells in steady state"; Baillieres
Best Pract. Res. Clin. Haematol. 12, 19-26; Mar-Jun, 1999
102. Korbling M; "In vivo expansion
of the circulating stem cell pool"; Stem Cells 16 Suppl 1, 131-138;
103. Kessinger A, Sharp JG; "Mobilization
of blood stem cells"; Stem Cells 16 Suppl 1, 139-143; 1998. Review
of cord blood stem cell transplants
Reference.Updated June 25, 2001
Other Clinical Uses of Adult Stem Cells David A. Prentice 22
104. Huhn RD; "Umbilical cord
blood stem cell transplantation and banking"; N J Med 97, 53-57;
105. **"Bibliography. Current
world literature. Hematopoietic stem cell transplantation"; Curr.
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