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Autologous Transplant

  

Main  | Allogeneic | Autologous | Cord Blood | Mini | Harvesting Stem Cells | Graft vs Host Disease

Treatments > Stem Cell Transplants > Autologous

Last update: 05/15/2008

PubMed TOPIC SEARCH: Review | Therapies | ASCO | Medscape (free login req.)

Q&A | Resources | Research News

Background:  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:
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

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, one study comparing SCT types 

About Autologous  Stem Cell Transplant (AutoSCT)  

In an autologous stem cell transplant, stem cells from the patient's own marrow are "harvested," stored and then returned to the body (engrafted) after the patient receives high doses of chemotherapy and/or radiotherapy conditioning therapy. 

Sometimes, the portion of marrow is also purged of cancer cells before being returned to the patient.  Click the illustration to the right (Source: makna.org.my/bonemarrow.asp)

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 autologous transplants are done in four phases:
 

  1. Induction phase - conventional doses of chemo are used to reduce disease.

  2. Mobilization/harvesting phase - use of growth factors or other treatments that leads to the proliferation and mobilization of stem cells from the bone marrow into the bloodstream. These cells are then harvested using a process called apheresis in order to replace the stem cells that will be ablated (killed) during the conditioning phase of treatment.  

    What is apheresis?  medlib.med.utah.edu
    "The process of apheresis involves removal of whole blood from a patient or donor. Within an instrument that is essentially designed as a centrifuge, the components of whole blood are separated. One of the separated portions is then withdrawn and the remaining components are retransfused into the patient or donor."

  3. Conditioning phase - high-dose therapy that wipes out or "conditions" the immune system and bone marrow in preparation for the stem cells harvested previously.  This phase might include Total Body Irradiation (TBI), and more recently, high dose bexxar - an investigational alternative to TBI.

  4. Engraftment phase - the stem cells 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." -      cancer.med.umich.edu 

    Treatment for delayed engraftment? 

    GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.
    Exp Hematol. 1991 Mar;19(3):191-5. PMID: 1995310 

    The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis (production of granulocytes), but the effect is transient in some patients.

Potential Advantages of Auto Transplants:

High dose therapies made possible by prior harvesting and subsequent engraftment may:
 

decrease risk of disease recurrence and/or curing aggressive component of the disease. 

produce a durable remission.

Avoid Graft versus Host disease 
(compared to allogeneic SCT)

Potential Problems with Auto Transplants:

Engrafted cells can be contaminated with disease (compared to allogeneic SCT)

Increases risk of MDS/secondary AML 

High Treatment Related Mortality (TRM)
 

Regimen related toxicity

Infection during and following conditioning therapy until engraftment takes.

 

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

BMTinfoNet  bmtinfonet.org
 
Highly recommended.  A nonprofit that specializes in SCT information and support.
About transplants  bmtinfonet.org 
Search for Stem cell Transplant Centers  BMTinfoNet 
 
Also provides: background, Number of Transplants done, 
Minimum Donor Match Criteria, Contacts, Support Groups Available
  
Bone Marrow Transplant (BMT)  makna.org 
Understanding your Transplant  cancer.med.umich.edu
Managing Indolent Lymphomas in Relapse  asheducation.org  
Working Our Way Through a Plethora of Options (includes SCT guidance)
Blood and Marrow Transplant Resources  www.bmtresources.org
7 Phases of the Transplant Process  bmtresources.org
High-Dose Therapy and Autologous Hematopoietic-Cell Transplantation for Follicular Lymphoma Beyond First Remission: The Stanford University Experience - Biology of Blood and Marrow Transplantation 7:294-301 (2001)  PDF | PDF-Help
SCT for Low grade Lymphoma  asheducationbook.org /2004 full text | PAL's readable version
"In Section III, Dr. Koen Van Besien provides a well-documented update on outcomes associated with autologous and allogeneic stem cell transplantation for FL. The results of trials of autologous stem cell transplantation in first remission and recent data supporting a role for graft purging are discussed. Based on the premise that a graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic transplantation is the preferred approach in many cases, and recently reported results are summarized. Criteria for patient selection and the optimal role of transplantation in the overall therapeutic plan for the patient with FL are presented."
Support group for SCT
ACOR BMT-Talk  Support Groups
Types of Transplants & Diseases Transplanted  MSKCC
Survivorship & Support  MSKCC  
Patient SCT Stories  Cyberfamily  | What to take to Hospital  Cyberfamily
The Role of Autologous Transplantation in the Management of Mantle Cell Lymphoma: 
A Study From the EBMT E. Vandenberghe, C. Ruiz de Elvira, P. Isaacson, E. Lopez-Guillermo, E. Conde, 
C. Gisselbrecht, F. Guilhot, A. Goldstone, N. Schmitz  PDF | PDF-Help 

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Research News

Outcome: Radioimmunotherapy with 131-I tositumomab (Bexxar) enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation.   ASCO 2007

Conclusions: The addition of 131-I tositumomab to BEAM and autologous stem cell transplant for relapsed or high-risk chemosensitive DLBCL produces a 3-yr OS of 81% without excess toxicity. This compares favorably to historical controls. This regimen is currently being tested in a phase III trial in the BMT/CTN of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with relapsed chemosensitive DLBCL.
Outcomes: High-Dose Therapy (HDT) and Autologous Stem-Cell Transplantation (ASCT) in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome  J Clin Oncol. 2007 Dec 10;   PMID: 18071187 

This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.
Pilot study: High activity [escalating doses of] Zevalin® with peripheral blood progenitor cells support [followed by ASCT]  in patients with refractory/resistant B-cell non-Hodgkin lymphomas  blackwell-synergy.com

... high-activity Zevalin® with ASCT is feasible and could be safely delivered in elderly and heavily pretreated NHL patients, including those who previously received high-dose chemotherapy and ASCT.
Expert review Autologous transplantation for follicular lymphoma? Not too soon! - bloodjournal.hematologylibrary.org

The overall role of ASCT in follicular lymphoma continues to be debated. It is an excellent treatment option for the management of younger patients with recurrent disease.4 In advanced newly diagnosed lymphoma, a survival advantage has yet to be shown; with more prolonged follow-up it may still emerge in the GLSG study.
Harvesting stem cells: Intermediate dose etoposide plus G-CSF 16 g/kg is more effective than cyclophosphamide 4 g/m(2) plus G-CSF 10 g/kg in PBSC mobilization of lymphoma patients.
Leuk Lymphoma. 2007 Oct;48(10):1950-60. PMID: 17917963 

Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.
Prognostic factors & auto SCT: The pre-transplant FLIPI Index is associated with survival of follicular lymphoma patients undergoing autologous stem cell transplantation.
Leuk Lymphoma. 2007 Oct;48(10):1961-7. PMID: 17917964 

The association of FLIPI with survival appeared to be more relevant for patients who received standard conditioning regimens compared to those that were treated with high-dose radioimmunotherapy (p = 0.004). 

Among all patients, mortality was also associated with chemosensitive disease (HR = 0.47, p = 0.01) or untreated relapse (HR = 0.20, p = 0.0002) vs. chemoresistant disease, and >/=2 extranodal sites (HR = 2.82, p = 0.03) after adjusting for FLIPI. 

These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT.
The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma  nature.com 
High-Dose Bexxar®  with Stem Cell Support Effective in Elderly B-Cell NHL   professional.cancerconsultants.com 

"In the current study, 24 patients older than 60 years with refractory or relapsed B-cell lymphoma were treated with myeloablative doses of Bexxar followed by autologous stem cell infusions. Patients in this study were a mixture of high and low-grade NHL. This was a heavily pretreated group of patients and over half were deemed resistant to treatment. These authors reported a 3 year overall survival of 59% and a progression-free survival of 51%. There were no treatment-related deaths and toxicities were generally mild."
Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning [mini alloSCT] after failed [conventional] myeloablative hematopoietic cell transplantation.
J Clin Oncol. 2006 Sep 1;24(25):4150-7. Epub 2006 Aug 8. PMID: 16896000 

Factors associated with better overall survival were PR or CR (P = .01) and lack of comorbidity (P = .03) at HCT and absence of acute GVHD after HCT (P = .06). CONCLUSION: Encouraging outcomes were seen with allogeneic HCT after nonmyeloablative conditioning in selected patients who had experienced relapse after a high-dose HCT, particularly in patients with non-Hodgkin's lymphoma. Results with unrelated grafts were comparable with results with related grafts.
A long-lasting third complete remission after second autologous transplant followed by maintenance treatment with rituximab in a patient with diffuse large cell non-Hodgkin's lymphoma. 
Am J Hematol. 2006 Aug 2: No abstract available. PMID: 16886214
A Phase I/II Trial of High-Dose Yttrium 90 ibritumomab tiuxetan in Combination with High-Dose Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Patients with Poor-Risk or Relapsed Non-Hodgkins Lymphoma (NHL). Blood. 2005 Jul 7; PMID: 16002426 

No outcome data, but ... "We conclude that high-dose (90)Y ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without increase in transplant-related toxicity or delayed engraftment."
Radioactive Anti-CD 20 Antibody (Bexxar®) May Improve Outcome of Autologous Transplants for Follicular Lymphomas  cancerconsultants.com
Phase I Trial of Iodine-131 Tositumomab (Bexxar) With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Relapsed Non-Hodgkin's Lymphoma  jco.org
High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma.  [BEAM is the winner.]
Bone Marrow Transplant. 2004 Jul 26 PMID: 15273714 | Related abstracts
Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma - results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Blood. 2004 Jul PMID: 15238420
Rituxan® Prior to Autologous Stem Cell Transplantation may Improve Outcomes in non-Hodgkin's Lymphoma  www.ufscc.ufl.edu 
Autologous bone marrow transplantation for marginal zone non-Hodgkin's lymphoma.
Leuk Lymphoma. 2004 Feb;45(2):315-20. PMID: 15101717 | Related abstracts
[872] Long Term Results of Radioimmunotherapy with Bexxar/BEAM and Autologous Stem Cell Transplantation (ASCT) for Chemotherapy Resistant Aggressive  ASH 2003
Auto SCT - treatment-related mortality: Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitor-cell transplantation for lymphoma. Bone Marrow Transplant. 2004 Jan 19 PMID: 14730338
Auto SCT: Rituximab and ICE (RICE) as second-line therapy prior to autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 Jan 22 PMID: 14739217
ASH 2003  Long Term Relapse Free Survival Is Possible after Auto SCT for fNHL
Immunotherapy w/ autoBMT  medscape (free login req.) 
CD34+-Enriched Peripheral Blood Progenitor Cell Collections in Lymphoma Autotransplants Are Associated With Increased Morbidity,  Hillard M. Lazarus et al.  PDF
Involved-Field Radiation Therapy as an Adjunct to the Autotransplant Preparative Regimen for Lymphoma
David P. Schenkein, et al.  PDF mmserver.cjp.com
COMPARING WITH SALVAGE TREATMENT: Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of  chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. PMID: 7477169  PubMed
FRONT LINE TREATMENT: Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study. Bone Marrow Transplant. 2000 Nov;26(9):971-7. PMID: 11100276  PubMed
EFFICACY DATA: Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood. 1999 Nov 15;94(10):3325-33. PMID: 10552941 PubMed abstract
EFFICACY DATA: High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol. 2000 Feb;18(3):527-36. PMID: 10653868 PubMed abstract
OPTIMIZING: Improve the Outcome of Autologous Hematopoietic Cell Transplantation!  Karl G. Blume Stanford University School of Medicine, Stanford, California  WEB | Full-PDF | PDF-Help 
OPTIMIZING: Bcl-2 clearance: optimizing outcomes in follicular non-Hodgkin?s lymphoma  Bone Marrow Transplant
2002 Feb;29 Suppl 1:S14-S17. PMID: 11840156
REVIEW: Graft purging in autologous bone marrow transplantation: a promise not quite fulfilled.
Oncology (Huntingt). 2004 Jun;18(7):867-76; discussion 876-8, 881, 884. Review. PMID: 15255171 | Related articles
REVIEW: Role of autologous bone marrow transplantation in non-Hodgkin's lymphoma. Hematol Oncol Clin North Am. 1993 Jun;7(3):577-90. Review. PMID: 8102135  PubMed abstract
REVIEW: Bone marrow transplantation for non-Hodgkin's lymphoma: a review. Am J Med Sci. 1997 Apr;313(4):228-35. Review. PMID: 9099153 abstract
REVIEW: Biology of Blood and Marrow Transplantation (abstracts for Lymphoma)  www.bbmt.org  
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