Doctors at Johns Hopkins say Pamela Newton is the first adult worldwide to be cured of sickle cell disease using an experimental bone marrow transplant.
Fifteen months ago, the pain from Pamela Newton's sickle cell disease was excruciating. She spent more time in the hospital than in her Capitol Heights apartment. She was on 15 pain pills a day, all heavy narcotics. She was bleeding regularly and needed daily transfusions of platelets.Today, doctors at Johns Hopkins Hospital say that Newton is one of the first adults in the world to be cured of sickle cell disease - and the first using an experimental bone marrow transplant that could cure thousands like her who have been told they will never get better.
Word of a breakthrough gives hope to the roughly 80,000 Americans - and millions around the world - who suffer from this debilitating and usually fatal disease, which is predominant among African-Americans and Hispanics.Bone marrow transplants have been used to treat sickle cell disease for 20 years - but almost all of the 200 cured have been children. The treatments - high doses of chemicals that knock out the patient's own marrow before the transplant - are so toxic that adults with sickle cell-induced organ damage would be unlikely to survive them.
Brodsky said his team's procedure, developed by Dr. Ephraim Fuchs and Dr. Leo Luznik, is less toxic. They say they no longer believe they have to destroy as much of the patient's marrow as they once did - so they administer just enough chemotherapy to suppress the immune system. That dose keeps patients from rejecting the new marrow without harming their organs.This change allows transplants for adults, as well as children. Because the procedure occurs later in life, it relieves parents of the burden of making the decision for their youngsters (even in children, the sickle-cell transplant mortality rate is 5 percent to 10 percent). Instead, it allows the adult patient to see how severe the disease is before deciding whether to have a transplant.
Another transplant obstacle has been finding a perfect bone marrow match - a full sibling's marrow provides the best chance. But there's only a 25 percent chance that even a full sibling will be a match. And since sickle cell is inherited, siblings may also have the disease. That leaves about a 10 percent chance that a patient will find a suitable donor. Brodsky's procedure requires just a half-match - meaning that children and parents of the patient could be suitable donors.
Three days after the transplant, the patient is given a high dose of a drug called cyclophosphamide. Just as the bone marrow is taking root, the drug kills off the donor's lymphocytes - blood cells that are part of the immune system.
The cyclophosphamide spares the donor's stem cells and allows them to establish new blood cells and a new immune system. The nascent immune system is re-trained to see the patient's body as friend, not foe. This prevents the patient from rejecting the transplanted bone marrow - and prevents the newly developing immune system from http://www.baltimoresun.com/news/health/bal-te.sickle30mar30,0,6112155.story
Adult Stem Cell Transplant Follow up by Natasha Dussard 7/2004 - Natasha is an adult with sickle cell disease who saved stem cells from the cord blood when her daughter was born. These cells were transplanted at the University of Chicago in 2002. Here is a follow up report:
I'm the one that had the bone marrow/stem cell transplant done at University of Chicago, but was looking into having in done at Grady or Emory a couple of years ago. As of of May, I am 2 years out of the transplant. :) I just recently had a bone marrow biopsy and it said that I am 60-70% donor marrow now and that's where it will probably stay. I'm still taking anti-rejection meds (like Prograf) for the time being because the doctor is still being ultra cautious. It didn't help that he went to a sickle cell conference a couple months back and heard that another doctor's patient rejected after well over a year. But better to be cautious than to blow the whole operation.
I still am going to doctors, although they are not hematologists, I need to have surgery done for my back. Due to the sickling for so many years, my bones have degeneration problems. One of my discs is totally gone and is causing alot of pain. That is one thing that I was not expecting. I thought that I would have pretty much home free after having the transplant, but the overall years of sickling left it's mark. Now I see the reason to have this procedure done the younger the better. But overall, what I go
through now is still better than having the full blown disease. I still have the trait because my daughter (who was my donor) has it, so I still feel some sickling once in awhile, but nothing like before.
First Unrelated Stem Cell Transplant Performed in Atlanta December 12, 1998 - 1 year update
Doctors from Emory University Department of Pediatrics, Hematology-Oncology-Bone Marrow Transplant in have completed the world's first "unrelated donor" cord blood stem transplant in a child with sickle cell anemia. Keone Penn of Snellville, Georgia, a 12-year-old with sickle cell disease and a stroke when he was 5 was the recipient.
Keon was followed by the Pediatric Sickle Cell Team at the Georgia Comprehensive Sickle Cell Center at Grady Health System receiving chronic monthly blood transfusions ever since he had the stroke. Currently the only methods of preventing future strokes is lifelong monthly transfusions or to have a bone marrow transplant that completely replaces the patients blood making factory with donor cells. Atlanta and the Emory - Grady Sickle Cell team lead the United Sates in the most children successfully transplanted with 10 children cured of sickle cell disease. Keon did not have a brother or sister match, so the next logical step was to use stem cells from umbilical cord blood from an unrelated donor. This should open the door for many more patients who do not have a close match but have enough complications to go through the risk of the procedure.
At the bone marrow transplantation for sickle cell anemia national collaborative study meeting in December of 1998 the following results were presented: At 47 participating centers, with 9198 total patients, 627 or 7% meet the criteria for transplantation. 188 patients were HLA typed and only 82 had HLA matched siblings identified as donors. 49 of these patients have been transplanted, 2 died of graft vs. host disease, and 4 patients have had return of sickle cell disease. The probability of event free survival is 84%. 1,2 The problem has the lack of HLA matched related donors. Using stem cells from cord blood samples from unrelated donors have the best promise of meeting this need. Keon Penn was the first patient to undergo this procedure.
- Walters MC, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med. 1996 Aug 8;335(6):369-76.
- Walters MC, Patience M, Leisenring W, Rogers ZR et al Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions. . Biol Blood Marrow Transplant 1997 Dec;3(6):310-5
'Gentler' treatment for sickle cell hailed
Patricia Guthrie - Staff
Friday, October 26, 2001 Atlanta Journal Constitution
A "kinder, gentler" new bone marrow transplant may lead to the cure of more
people with sickle cell disease.
Controlled studies of the therapy will begin in a few months at 25 hospitals
around the country, including Children's Healthcare of Atlanta and Grady/Hughes Spalding Children's Hospital.
Known as "partial chimerism," the procedure uses a mixture of the patient's
bone marrow and a donor's bone marrow that combine to form healthy new blood cells. It allows for a patient's bone marrow not to be destroyed.
Currently, bone marrow transplants are of limited use for people with sickle cell
disease, because adults and some children can't endure the procedure. Under
the new therapy, it will no longer be the goal to totally wipe out and replace bone
marrow, where red and white blood cells and platelets are made.
"The new protocol is let's go ahead and aim for the mixture so that it will allow
transplants to be open to more people," explained Dr. Lewis Hsu, a pediatric
sickle cell specialist at Emory University School of Medicine who is affiliated
with Children's Healthcare and Grady's Sickle Cell Center. "This could be the
start of a very big step in the treatment of the disease."
Sickle cell disease, a genetic condition, affects 70,000 Americans, 95 percent of
them African-American. Between 4,000 and 6,000 Georgians suffer from it.
For some children with sickle cell disease, standard bone marrow transplants
using a patient's sibling as a donor have provided a cure that long eluded
doctors. The treatment is no longer considered experimental and has a success
rate of 85 percent, doctors say. More than 100 children have undergone the
procedure nationally, and the doctors at Children's Healthcare of Atlanta have
performed more of the transplants than any other.
Eight-year-old Bryce Payton of Lithonia was given a new life from the bone
marrow of his big brother, Chase, earlier this year. "He's 100 percent free of
sickle cells," said his father, Terrence Payton.
Bryce and Chase underwent the bone marrow transplant March 1, the same day
President Bush toured the AFLAC Cancer Center and Blood Disorder Service at Egleston hospital.
"He was actually in the room when the new bone marrow was being infused into
Bryce," Terrence Payton said of Bush. "And he told his older brother what he did made him a hero."
In the past, procedures such as the one Bryce endured during a monthlong
hospital stay would have been considered a failure had his bone marrow not
been eliminated completely, or if it had come back with the crescent-shaped,
sticky, sickled red cells. It would have meant that the bone marrow graft did not
But doctors in Seattle, Atlanta and Oakland, Calif., discovered that not to be true in five young patients. They were deemed cured of the disease one year after transplantation, even though their blood contained some sickled cells. But they experienced none of the typical infections or pain of the disease.
The mixed-blood partial chimerism therapy has proven successful in other
diseases as well. Mixing the two bone marrows involves a delicate balance of
acceptance and tolerance.
"The host and donor blood tolerate each other, put up with other and not reject
each other," Hsu explained. "It's making it kinder and gentler, maybe less
There are, however, risks with the new therapy. The chances of graft rejection
could be higher. Rejection can be fatal or can lead to chronic graft-versus-host
disease that attacks skin, lungs and other organs.
Initially, only 30 children nationwide will receive the new therapy. The results
won't be known for at least a year.
Also see: "Mixed Chimerism Following Bone Marrow Transplantation-As Treatment For Sickle Cell Disease" Children's Hospital Oakland - http://hemonc.cho.org
Questions and Answers on Bone Marrow and Cord Blood Stem Cell Transplants
Question: How is the Cord Blood Stem Cell transplant like Bone Marrow transplant ?
Answer: The preparation considerations are similar. the Cord Blood Stem Cell donor is unrelated and is an alternative for patient without a brother or sister match. The cost , time, and follow-up are similar. However, the risks of graft versus host disease and graft rejection are higher, because the immunologic matching for an unrelated donor is never quite as perfect as with a matched relative donor.
Question: What is the cost and the steps to consider for bone marrow transplant?
Answer: Evaluation for Bone Marrow Transplantation is a long journey, because the risks and expenses are large. Here is an outline of what we would need to do to evaluate a child for possible bone marrow transplantation. We would certainly plan for many hours of discussion if you are interested in proceeding, but I wanted to make sure that you have a rough idea of the stepwise process:
1) SICKLE CELL ELIGIBILITY -- determine whether your son has had severe enough sickle cell disease to make the risks of bone marrow transplant worthwhile. A summary of his medical history would be very helpful, focusing on whether he has had stroke and chronic transfusion, or very frequent hospital stays for pain or for lung problems, or other major sickle cell problems. This can be done by fax or e-mail.
2) OTHER MEDICAL ISSUES --- You should make your doctor aware that your family is considering the bone marrow transplant (BMT) option. Ask the doctor to let us know whether there are any hidden medical problems that would influence the decision, such as chronic viral or other infections, problems with transfusion reactions, other medical problems unrelated to sickle cell, or anything else unusual. This does not have to be a lengthy or formal statement from the doctor at this point, more like a safety check to make sure that we are not missing any huge medical issues. A more complete medical record would be required later.
3) HLA-TYPING BLOOD TESTS --- Do immunologic typing (HLA typing) of your child and the relative with the highest probability of matching him - only brothers or sisters from the same parents are really potential donors, parents and half-siblings are very unlikely to match unless there was an unusual family tree. The HLA typing will cost several thousand dollars. If the sibling is not a full HLA match, then it is very unlikely that BMT can be done.
4) PRE-BMT EVALUATION -- after all of the above steps, then a formal evaluation by the BMT team can begin. This will include a very detailed look at his medical history and current medical condition from head to toe, plus your family's ability to cope with the BMT process. Parents will need to plan to stay in the Atlanta with the patient for a minimum of 8 months for the pre-transplant evaluation, transplant stay, and post-transplant follow-up. A financial arrangement will need to be made, with an estimated cost for the BMT process of $150,000 to $250,000. An outside expert panel will review the case on ethical grounds.
5) BMT & early follow-up period - This is a risky process, and the statistics are that there is a 5% to 8% chance of death. Death can be caused by infection, bleeding, toxic effects of the treatment, or the new bone marrow engrafting and then attacking the rest of the body. There is also a 10% to 12% chance that the child could go through the BMT process but reject the new bone marrow, ending up still having sickle cell disease. Therefore, the overall success rate of BMT for sickle cell disease is approximately 80% to 85%, of being cured of sickle cell. These require close medical followup, often in and out of the hospital and office daily, and many medications daily.
Question: How is the Cord Blood Stem Cell transplant like Bone Marrow transplant
Answer: The preparation considerations are similar. the Cord Blood Stem Cell donor is unrelated and is an alternative for patient with out a brother or sister match. The cost , time, and follow-up are similar.
Question: I have a daughter that have sickle cell. If she would have a step sibling. Could she receive a bone narrow transplant if they match? What risk would it be if they do match an her body rejects the transplant?
Answer: The main concerns with sickle cell bone marrow transplantation are (1) the immunologic match between donor and recipient (HLA types) and (2) the health status of your daughter.
1) A full HLA match between brothers or sisters will have the very best chances for successful bone marrow transplant (BMT). Lesser degrees of match means greater chances of two bad outcomes:
1a) Graft Rejection (your child goes through the BMT process but at the end her own bone marrow grows back and she still has sickle cell disease) or 1b) Graft Versus Host Disease (GVHD - the transplanted marrow attacks the rest of your child's body as foreign tissue and can cause great damage.
1c) very seldom will a person have a full HLA match with half-siblings or parents, unless the family tree is very inbred (for example, everyone is from the same isolated village or clan and all are related to each other's cousins. Therefore, your child's step-sister would not have a high chance of being an HLA-matched donor for BMT.
2) In addition to the chances of the two types of problems listed above (Graft Rejection and GVHD), there is a third set of bad problems that are side effects of the harsh BMT treatment process. Death may occur due to overwhelming infection,uncontrollable bleeding, and failure of organs such as liver or kidney or lungs. The chances that these bad side effects will occur are probably greater if your child is in worse health going into transplant. Therefore, the general feeling among sickle cell doctors in North and South America is that the only patients with severe sickle cell complications should be offered BMT (because only then are the high risks worthwhile), but that they be in relatively good physical condition. Your child may or may not meet these eligibility criteria.
HLA Matching for Bone Marrow Transplant
Question: What does HLA matched mean?
Answer:The short answer is: HLA match = immunologic match.
The HLA markers on the surface of cells are what allows the body to recognize that these cells are its own ("self") or somebody else ("non-self"). Usually we test for HLA in three classes: HLA-A, HLA-B, and HLA-DR, but there are additional surface markers which are not tested for. Each person has two possible inherited types in each of these classes, which are designated by numbers such as HLA-A4, A8 HLA-B27, B19 HLA- DR 1, 11. When all 6 of these are identical between a pair of siblings, they probably inherited all the same immunologic markers from their parents, and their cells cannot be distiguished as different by the immune system. This is the ideal set-up for a bone marrow donor and host: HLA-matched siblings.
Any mismatch in the HLA types of two siblings means that they inherited different types from their parents, and that would not be a good set-up for bone marrow transplant.
Finally, HLA-matching of unrelated people can be done, drawing from computerized registries of tens of thousands of people willing to be bone marrow donors (e.g. US National Marrow Donor Program, others in other countries). However, these unrelated people may match at all 6 of the markers for HLA-A, HLA-B,and HLA-DR but not match at some of the other surface markers because they are not from the same parents. The donor cells would have a fairly high chance of being recognized as foreign.
In each case of a mismatch, greater mismatch in HLA type means higher chances of two bad outcomes: (1) that donor cells would be attacked by the host immune system (graft rejection), or (2) the immune system that grows from the donor cells would attack the host (graft vs. host disease). Also, children have less risk of graft vs host disease than adults with BMT.
For this reason, essentially all of the sickle cell BMT have been from HLA-matched sibling donors, for a child as the transplant recipient. The graft vs host disease rate has been relatively low for sickle cell children, but the graft rejection rate is higher (10-12%) than that for BMT as cancer treatment. Why the graft rejection rate is high for sickle cell BMT is not understood. Matched unrelated donors from the National Marrow Registry have not been used for sickle cell BMT, although one matched unrelated cord blood stem cell from the New York Cord Blood Registry has been used (Atlanta, Dr. Andrew Yeager)
You might find additional information about bone marrow transplant in broad terms from the National Marrow Registry website. Info about HLA typing may be available from organ donation and organ transplant centers, since the same HLA matching is done for transplants of heart, lungs, liver, kidney, etc. to prevent rejection of the transplanted organ.
Question: How can I get a consultation about bone marrow transplant
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or call the Comprehensive Sickle Cell Center at 404-616-3572
Bone Marrow and Cord Blood Stem Cell Transplant Web Links
Bone Marrow Links
Cord Blood Links
At present, there is no coordinated nation-wide donor system for cord blood as there are for whole blood, bone marrow, kidneys and other organs for transplantation. The American Red Cross has cord blood collection programs in Portland, OR; San Diego, CA; St. Paul, MI; Columbus, OH; and Worchester, MA. Fifteen to 20 other programs will begin operations by 2002.
We offer free cord blood services to families who currently have a child
with sickle cell anemia or thalassemia and are having another child. In
the first two years of our program, we collected 732 cord bloods in 45
states. Our cord blood services are designed to help families who give
birth at community hospitals. Once the cord blood unit is collected, it is
sent to us for analysis, processing and storage. The family owns the
unit. Cord blood and affected child HLA typing are performed. All
results are sent to the physician and family. Informed consent is
required prior to enrollment. If a family decides to use the cord blood
for a transplant, the unit is shipped to a transplant center selected by
the family. We have personally released 9 units for children who have
sickle cell anemia or thalassemia for transplantation. All have been
cured of their disease. We feel that it is important for families not to
miss the chance to collect cord blood if they already have a child with
sickle cell anemia.
FamilyCord offers private cord blood storage and has over 30 years of cryopreservation experience. We also have programs that may be beneficial to sickle cell anemia patients including a public donation option and an immediate needs transplant program, which makes free cord blood banking available to families in need of treatment. Please refer to the following pages for more information: Home page: http://www.familycord.com
Immediate need transplant: http://www.familycord.com/immediateneeds.cfm
Public donation option: http://www.familycord.com/faq_publicdonation.cfm
Stem Cell Transplant Review by CIGNA Insurance Company at http://www.cigna.com/customer_care/healthcare_professional/coverage_positions/medical/mm_0464_coveragepositioncriteria_stem_cell_transplant_sickle_cell_disease.pdf
Adamkiewicz TV, Mehta PS, Boyer MW, Kedar A, Olson TA, Olson E, Chiang KY, Maurer D, Mogul MJ, Wingard JR, Yeager AM. Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease. Bone Marrow Transplant. 2004 Jul 12 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247929
"Bone Marrow Transplantation without Myeloablation for Sickle Cell Disease" L. Krishnamurti, M.D.; Bruce Blazar, M.D.; John Wagner, M.D. University of Minnesota. N Engl J Med, Vol. 344, No.1; page 68; January 4, 2001.
For questions regarding non-myeloablative BMT for SCD, Dr. Lakshmanan
Krishnamurti can be reached at (612) 626-2778 or E-mail:
Amado RG, Schiller GJNonmyeloablative approaches to the treatment of sickle
hemoglobinopathies.Semin Oncol 2000 Apr;27(2 Suppl 5):82-9
Blau CA,Current status of stem cell therapy and prospects for gene therapy for
the disorders of globin synthesis.Baillieres Clin Haematol 1998 Mar;11(1):257-75
Nietert PJ, Abboud MR, Silverstein MD, Jackson SMv, Bone marrow transplantation versus periodic prophylactic blood transfusion in sickle cell patients at high risk of ischemic stroke: a decision analysis. Blood 2000 May 15;95(10):3057-64
Walters MC, Storb R, Patience M, Leisenring W, Taylor T, Sanders JE, Buchanan GE, Rogers ZR, Dinndorf P, Davies SC, Roberts IA, Dickerhoff R, Yeager AM, Hsu L, Kurtzberg J, Ohene-Frempong K, Bunin N, Bernaudin F, Wong WY, Scott JP, Margolis D, Vichinsky E, Wall DA, Wayne AS, Pegelow C, Redding-Lallinger R, Wiley J, Klemperer M, Mentzer WC, Smith FO, Sullivan KM. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Blood. 2000 Mar 15;95(6):1918-24.
Bone Marrow Transplant Centers for Sickle Cell Patients
Atlanta, GA: Emory University and Grady Memorial Hospital
Augustin, GR: University of Bonn
Birmingham, UK: The Birmingham Children's Hospital NHS
Boston, MA: Dana Farber Cancer Institute, Children's Hospital, Harvard University,
Boston Comprehensive Sickle Center
Chapel Hill, NC: University of North Carolina
Chicago, IL: University of Illinois
Columbia, NC: Richland Memorial Hospital
Creteil FR: Hopital Henri Mondor
Dallas, TX: University of Texas, Southwestern Medical Center at Dallas
Denver, CO: University of Colorado, Sickle Cell Research & Treatment Center
Durham, NC: Duke University
Gainesville, FL: University of Florida; Shands Teaching Hospital
Hackensack, NY: Hackensack Medical Center
Houston, TX: MD Anderson Cancer, University of Texas
Indianapolis, IN: Indiana University
London, UK: Royal Postgraduate Medical School; Hammersmith Hospital
Los Angeles, CA: University of Southern California, Children's Hospital of LA
Memphis TN - Paul Woodard, MD Hematology/Oncology Division of Stem Cell Transplantation St. Jude Children's Research Hospital Memphis, TN 38105-2794
(901) 495-4239 Fax (901) 521-9005
Miami, FL: University of Southern Florida
Milwaukee, WI: Medical College of Wisconsin, Midwest Children's Cancer Center
New Haven, CT: Yale University
New Orleans, LA: Tulane University
New York, NY: Methodist Hospital
Oakland, CA: Children's Hospital of Oakland
Philadelphia, PA: Children's Hospital of Philadelphia, University of PA
St. Louis, MO: Cardinal Glennon Children's Hospital, University of St.Louis
St. Petersburg FL: University of South Florida, All Children's Hospital
Sao Paulo, BR: University of Campinas
San Francisco, CA: University of California at San Francisco, San Francisco General Hospital, Comprehensive Sickle Center
Seattle, WA: University of Washington, Fred Hutchinson Cancer Research Center
Stanford, CA: Stanford University
Toronto, ON: Hospital for Sick Children
Washington, DC: Children's Hospital National Medical Center, George Washington University, Howard University