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Patients Against Lymphoma

 

Harvesting Stem Cells

Last update: 10/14/2011

TOPICS
 
About | Agents that Mobilize Stem Cells | Q&A

What are adult stem cells? - Stem Cell Basics - stemcells.nih.gov 

"The history of research on adult stem cells began about 40 years ago. In the 1960s, researchers discovered that the bone marrow contains at least two kinds of stem cells. 

Hematopoietic stem cells form all the types of blood cells in the body. A second population of cells, called bone marrow stromal cells, was discovered a few years later. Stromal cells are a mixed cell population that generates bone, cartilage, fat, and fibrous connective tissue."

Stem cell image from lifeethics.org

 

Harvesting Stem Cells
from Donors

Harvesting Stem Cells
from Patients

Register to be a donor? 

call 1 800 MARROW2


A sample of your blood will be taken and typed. You will then be notified if a patient with the same HLA blood type has a need. 

In a Peripheral Blood Stem Cell Transplant (PBSCT), the donor  will receive medicine (Neupogen - G-CSF) a few days before collecting the stem cells. This forces the stem cells from the bone marrow into the general circulation. 

A catheter is placed (or an IV lines are placed into veins in each arm) and the donor's blood is "sucked out." The stems cells are removed and the blood is returned to the donor in a process called apheresis.

How long does it take? Typically it takes 1 day to collect the necessary number of stem cells from a healthy donor, unless the donor is of advanced age. 

If enough stem cells are captured, a bone marrow transplant will be done. If enough stem cells cannot be obtained from the peripheral circulation, the surgical bone marrow method can be used.

How are the stem cells mobilized? Usually following treatment with chemotherapy the patient will receive a growth factor medicine, such as G-CSF, a few days before collecting the stem cells. 

This forces the stem cells from the bone marrow into the general circulation (mobilization). 

A catheter is placed (or an IV lines are placed into veins in each arm) and the donor's blood is "sucked out." The stems cells are removed and the blood is returned to the donor in a process called apheresis.

How long does it take?  Typically it takes 3 to 5 days to collect the necessary number of stem cells - about  5 million CD34 expressing cells - per killogram of the patient's weight -  is the goal, but as few as 2 million cells have been used successfully in stem cell transplants.

Collection of stem cells from the patient is typically done in preparation for a stem cell transplant. 

This procedure can also be done following successful treatment (when few malignant cells are present) and the collected cells can be stored for future use when needed.  

Agents that mobilize stem cells
 - release these important cells into the peripheral blood

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Neupogen (colony-stimulating factor (G-CSF) / filgrastim) 

These data suggest that 'high-dose' filgrastim (12 ug/kg/day) has an acceptable short-term safety profile in normal PBSC donors and is reasonably well tolerated, although assessment of its long-term effects will require a longer follow-up.  Source:  ASCO.org
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AMD3100 (investigational) 

MOZOBIL is a new agent that aids in releasing stem cells into circulating blood where they can be collected by a process called apheresis."  Source: myeloma.org

Study:  http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_04-H-0078.html 
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High dose Cytoxan (a chemotherapy agent)

Both granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (CY) are employed in the clinic as mobilizing agents to stimulate the egress of haematopoietic stem/progenitor cells (HSPC) from bone marrow (BM) into peripheral blood (PB). 

However, although both compounds are effective, the simultaneous administration of G-CSF + CY allows for optimal mobilization [with additional anti-tumor effects].  Source: PMID 15679866 
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Peripheral blood stem cell mobilization with chemotherapy and granulocyte-colony stimulating factor in patients with hematological malignancies.  PMID:7570686 

Q&A  on stem cell harvesting

What to expect | How long can stem cells be stored?
What is portability?  | What about Insurance? | When to harvest stem cells? |
What about purging?

What to expect?

During the harvest, I think it's your calcium levels, can get out of whack. If they do you will start to feel tingling in your lips or possibly somewhere else. You tell your nurse and she will give you some Tums to chew on which quickly set things right. 

You will have a nurse with you constantly while harvesting cells. You're pretty much confined to the bed you're in for the duration because you are hooked up to the machine, so bring with you something to read, a computer or someone to chat with. Post harvest there really is nothing. Your cells will be either frozen there or sent somewhere to be frozen.  

~ source: Lay comment from Pooh-Bah

 
How long can stem cells be stored?
 

"After processing, PBSC are cryopreserved for later infusion. Controlled-rate freezing with temperature curve monitoring is required. Until required for infusion, products are stored in the vapor phase of liquid nitrogen. Usually the storage period is weeks to months; however, stem cell products have provided adequate engraftment when infused 10 years after cryopreservation

After thawing, PBSC again are checked for viability. Because granulocytes do not survive cryopreservation, loss of this cell fraction from the collection is expected. To allow survival during freezing and thawing, cells are placed in a medium containing 7.5-10% dimethyl sulfoxide. 

Because cells lose viability over a short period in this medium, infusing the cells immediately after thawing is important." 

Source: emedicine

 

What is portability?

Although preferred to be stored at the center of eventual transplant they are fully portable. It was not a consideration as they transport stored cells from center to center all the time as a standard practice. 

~ Source: RB (Lay comment)

 

Insurance coverage for harvesting?  

For stem cell transplant, the harvesting portion will be covered as part of the package. Otherwise your doctor will have to submit the rationale to the provider: that it is reasonable and/or there's a pressing need. Just banking for a relapse by itself probably will not be compelling enough with most insurance companies.  

Source: ~ KS & RB (lay comment)

When to harvest stem cells?

When it’s appropriate to harvest stem cells depends on many factors, such as one’s age and performance (the likelihood that the stem cells would be utilized) … but also the bone marrow status, and whether you have high or low risk lymphoma.

It can also be a judgment call – for example: could the cells be harvested later, when the decision to use them is made – instead of in advance for long term storage?

These are all questions that can only be addressed by a trained physician with first-hand information about your case. So you might consult an independent expert, ideally at a center that stores stem cells for future use – not every center does this.


=We propose, but only as a starting point for discussions with your doctors: 

A) You feel that you will require and be eligible for stem cell rescue
therapy in future (favoring younger age, good performance, higher-risk lymphoma)

Best timing?

B) A is true, and you've completed therapy and have minimal disease?

C) A is true, and just prior to therapy that is considered harsh on stem
cells (Fludarabine-based chemo / RIT)?

=A lymphoma expert commented: 

" [The proposal] sounds reasonable, however we don't typically harvest stem cells (without using them) in MCL or DLBCL in advance of immediately using."

=
Another expert wrote: 

"
To me, in fnhl stem cell harvest may take place after first CR (if any bad prognosis indicator is found), or after second CR. As for when to use them, to me, currently, second CR should almost always be consolidated with an autologous stem cell transplant (but this is only my opinion).

=A patient wrote: 

I completed CVP but did not achieve a persisting remission, so I was prescribed RCHOP. Before starting it, my oncologist suggested that on completion of that therapy, I should stockpile my stem cells in case of future transformation. His recommendation was that I take that opportunity before damaging my marrow/stem cells irrevocably with subsequent treatments (eg Fludara or RIT). Since my indolent follicular disease was not seen as appropriate for treatment with autologous stem cell transplantation, the stockpiling was solely to deal with the possibility of transformation to diffuse (aggressive) lymphoma for which autologous transplant might have some utility. The RCHOP cleared my marrow (at least in the area they biopsied) and was able to store stem cells in case I need them in future.

=Our experience (follicular):

Joanne had her stem cells harvested prior to Bexxar (RIT) in case an autoSCT was needed later. She had many prior treatments, including CHOP, and her marrow was clean (PCR testing) following low dose PEP-C. We felt the conditioning protocol for harvesting (high dose Cytoxan) would also debulk further, prior to RIT, giving her a better chance to get a durable CR from Bexxar. 

What about purging to remove lymphoma cells from harvested stem cells?

=We expect the answer of benefit from purging is dependent on clinical factors, including the lymphoma subtype and methods used to purge. 

"Purging of neoplastic cells for autologous stem cell transplantation is usually done in vivo by administering chemotherapy and/or other agents before harvesting. It is also possible to decrease malignant cells counts directly in the cell harvest."   http://www.ncbi.nlm.nih.gov/pubmed/15186735 

"In vitro purging is labour intensive, costly and, as yet, the effect on relapse is unclear." http://www.ncbi.nlm.nih.gov/pubmed/11840153 

Related report: Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation http://bit.ly/tk7sJ  

"Lymphoma contamination of transplanted apheresis products had no apparent impact on event-free and overall survival." Bone Marrow Transplantation (2001) 28, 207-212.

Topic Search:  ASCO | PubMed



Resources:

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About SCT emedicine.com 
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Blood Cancer Transplants: Peripheral Blood Cells Better Than Bone Marrow? cancer.gov 1-18-01
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Bone Marrow Donor
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National Marrow Donor Program marrow.org 
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Registering in various countries transweb.org 
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Steps of Marrow and PBSC Donation marrow.org
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Harvesting Stem cells 
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apheresis LymphomaInfo.Net
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What is apheresis? medlib.med.utah.edu

 

Research News:

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Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation http://bit.ly/tk7sJ  

"Lymphoma contamination of transplanted apheresis products had no apparent impact on event-free and overall survival." Bone Marrow Transplantation (2001) 28, 207-212.
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Chemotherapy time interval predicts NHL survival - 28/4/2006  - lymphoma-net.org 

The time interval between last chemotherapy and apheresis – the removal of whole blood – in patients with non-Hodgkin's lymphoma (NHL) due to undergo stem cell transplantation, appears to predict their likelihood of survival, US researchers have discovered.
  • Rituximab During PBSCT for Non-Hodgkin's Lymphoma - Immunotherapy With Rituximab During Peripheral Blood Stem Cell Transplantation for Non-Hodgkin's Lymphoma - Bloodline
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    Isolation and transplantation of highly purified autologous peripheral CD34(+) progenitor cells: purging efficacy, hematopoietic reconstitution in non-Hodgkin's lymphoma (NHL): results of Japanese phase II study. Bone Marrow Transplant. 2005 Jan 17; PMID: 15654349 | Related articles
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    [892] Increasing the Number of Apheresis Collections Increases Lymphocyte Collection and Affects Survival [+] after Autologous Stem Cell Transplantation for Non-Hodgkin Lymphoma. Session Type: Poster Session 46-I - ASH 2004
     
    "These data suggest that increasing the number of peripheral blood apheresis collections beyond the minimum number required to meet CD34+ collection targets may result in improved overall and progression-free survival mediated by an increase in autograft absolute lymphocyte count."
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    Time Interval from Last Chemotherapy to Stem Cell Collection Correlates with Peripheral Blood Absolute Lymphocyte Count at Apheresis and Survival Post-Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma. Session Type: Poster Session 197-III - ASH 2004
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    AMD3100 is a stem cell mobilizer. By blocking CXCR4, a specific cellular receptor, AMD3100 triggers the rapid movement of stem cells out of the bone marrow and into circulating blood. Once in the circulating blood, the stem cells can be collected for use in stem cell transplant. Stem cell transplant is a procedure used to restore the immune system of cancer patients who have had treatments that previously destroyed their immune cells. http://www.anormed.com/products/AMD3100/index.cfm 
     
    Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
    professional medical advice or to replace your relationship with a physician.
    For all medical concerns,  you should always consult your doctor. 
    Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.