Umbilical Cord Transplants Provide Same Outcomes as Related Allogeneic Stem Cell

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Umbilical Cord Blood

Human umbilical cord blood is a rich source of the stem and progenitor cells that are present in bone marrow. Cord blood from related donors has been successfully transplanted in many children worldwide. In addition, cord blood from unrelated donors has recently been successfully transplanted into children. However, there is still controversy over use in adults due to the relatively small number of cells infused per kilogram of body weight. Recent studies suggest that cord blood can be “expanded” in culture and can be used for adult transplants. In general, cord blood is utilized when no suitable family member or unrelated donor is available. Parents can also have the cord blood cryopreserved at the time of delivery of a child. This has been useful when a prior child has a disease treatable by marrow or blood tem cell transplantation and there is no other donor available.

Umbilical cord blood is cryopreserved in “cord blood banks”. HLA typing is performed and available for computer matching in the same way that the NMDP performs unrelated donor searches. Approved transplant centers are provided with the frozen cells when needed.

Currently the majority of units of cord blood has been provided by the New York Blood Center, which is funded by the National Heart Lung and Blood Institute (NHLBI). Participating Centers in the NHLBI study include the Dana Farber Cancer Research Center; the Fred Hutchinson Cancer Research Center, Seattle, WA; the University of California (UCLA) in Los Angeles; Children’s Hospital of Orange Co. Orange, CA; Indiana University, Indianapolis, IND; Duke University Medical Center, Durham NC; and the University of Minnesota, Minneapolis.

Umbilical Cord Blood an Acceptable Alternative for Stem Cell Transplantation

According to results from two studies recently published in The New England Journal of Medicine, hematopoietic stem cells from the umbilical cords of newborn infants provide an effective alternative to hematopoietic stem cells from the bone marrow of donors for an allogeneic stem cell transplant in patients with leukemia who cannot find a matched donor.

Stem cell transplantation is the only curative treatment option for some types of aggressive leukemias. Stem cell transplantation includes the use of high doses of chemotherapy and/or radiation. The higher doses of treatment tend to kill more cancer cells than moderate doses of treatment; however, the high-dose treatment regimens also tend to kill more healthy cells in the body, such as blood cells, leading to increased rates of severe side effects. Following the high doses of treatment, patients receive infusions of hematopoeitic stem cells, or immature blood cells that mature in the body, to replace the blood cells that are killed during treatment. In an allogeneic stem cell transplant, patients receive a donor’s hematopoietic stem cells following treatment. The donor’s cells must be “matched” to the patients, meaning that sequences of 6 specific proteins (HLA) found on the outside of the cells must be similar to that of the patients. If all HLA match between the donor and patient, it is referred to as a perfect match. Unfortunately, many patients in need of an allogeneic stem cell transplant cannot find a matched donor and are therefore denied treatment. Donor hematopoietic stem cells provide an added anti-cancer attack in that they attack the patients’ cancer cells. However, they also may attack the patients’ healthy tissues, resulting in a condition referred to as chronic or acute graft-versus-host disease (GVHD), which can lead to debilitating consequences.

Hematopoietic stem cells can be found in the bone marrow (spongy material inside large bones), circulating blood and the umbilical cord of infants at birth. Unfortunately, the rich source of stem cells within the umbilical cord is discarded in thousands of births that occur daily. Researchers have been evaluating the use of umbilical cord stem cells for the treatment of allogeneic stem cell transplants, in the hopes of utilizing them for patients who cannot find a donor match. Previous trials have indicated their effectiveness in transplants, as well as a reduction in GVHD with the use of mismatched hematopoietic stem cells. Trials are ongoing to determine the role of cord blood in allogeneic stem cell transplants.

The first study published in The New England Journal of Medicine included data obtained from the analyzed data from the International Bone Marrow Transplant Registry and the National Cord Blood Program.[1] The data included patients with leukemia who underwent an allogeneic stem cell transplant with either umbilical cord hematopoietic stem cells that had one (34 patients) or two mismatched proteins (116 patients), bone marrow hematopoietic stem cells with one mismatched protein (83 patients), or bone marrow stem cells that were a perfect match (367 patients). In this trial, patients who received cord blood tended to have more advanced disease and were a younger age than patients who received bone marrow. Overall mortality, treatment-related mortality and treatment failure rates were all superior among patients who were treated with matched bone marrow; however, these rates were similar among patients who were treated with mismatched cord blood or mismatched bone marrow. Treatment-related mortality was lowest among the patients who had matched bone marrow cells. At 3 years following treatment, cancer-free survival rates were 33% for patients who received matched bone marrow, 23% for patients who received cord blood, and 19% for patients who received mismatched marrow. Similarly, 3-year overall survival rates were highest for patients receiving matched bone marrow hematopoietic stem cells: 35% for those who received matched bone marrow cells, 26% for those who received cord blood, and 20% for those who received mismatched bone marrow cells. The rates of acute GVHD were similar among patients who received matched bone marrow and cord blood, while patients who received mismatched bone marrow had higher rates of GVHD. Chronic GVHD occurred more frequently among patients who received cord blood.

The second study published in the New England Journal of Medicine also compared results from patients with aggressive leukemia who received an allogeneic stem cell transplant with either cord blood (98 patients) or donor bone marrow (584 patients).[2] The data was reviewed from the Eurocord and the European Blood and Marrow Transplant Group in patients who received transplants between 1998 through 2002. All patients who received bone marrow had a perfect donor match, while only 6% of patients who received cord blood had a perfect match. Patients who received cord blood tended to have more advanced disease than those who received bone marrow. At 2 years, transplant-related mortality was 23% for both groups of patients. At 2 years, overall survival was 42% for those treated with bone marrow and 36% for those treated with cord blood. Cancer-free survival at 2 years was 38% for patients who received bone marrow and 33% for those who received cord blood. Upon analysis of several variables, there was no difference in survival between patients who received bone marrow or cord blood when patients were matched for the type of leukemia and stage of disease. Acute GVHD occurred in 26% of patients who received cord blood and 39% of patients who received bone marrow. Chronic GVHD occurred in 30% of patients who received cord blood and 46% of patients who received bone marrow.

The researchers from both studies concluded that cord blood represents a feasible option for a hematopoietic stem cell source in patients with aggressive leukemia undergoing an allogeneic stem cell transplant who are not able to find a matched donor. Patients who might benefit from an allogeneic stem cell transplant, but cannot find a matched donor may wish to speak with their physician about the risks and benefits of a transplant with the use of cord blood, or the participation in a clinical trial further evaluating transplants with cord blood. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.cancerconsultants.com. Personalized clinical trial searches are also performed on behalf of patients at cancerconsultants.com.

References:

[1] Laughlin M, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. New England Journal of Medicine . 2004; 351:2265-2275.

[2] Rocha V, Labopin M, Sanz G, et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. New England Journal of Medicine . 2004; 351:2276-2285.

According to an article recently published in Blood, using umbilical cord blood for stem cell transplants provides results that are similar to or better than results of an allogeneic stem cell transplant utilizing stem cells from a related donor.

Hematologic malignancies are cancers that originate in the cells of the blood. There are several different types of hematologic malignancies, many of which are treated with a stem cell transplant.

One type of stem cell transplant, an allogeneic stem cell transplant, involves the use of high-dose therapy to kill more cancer cells than standard doses. Unfortunately, the higher doses tend to destroy important hematopoietic stem cells (immature blood cells). These stem cells mature into red blood cells, which transport oxygen and nutrients to tissues in the body; white blood cells, which help the body fight infection; and platelets, which aid the blood in clotting.

Low levels of hematopoietic stem cells caused by high-dose treatment can result in life-threatening conditions. In an effort to prevent this condition, hematopoietic stem cells from a donor are infused into the patient following therapy. Hematopoietic stem cells may be obtained from umbilical cord blood immediately following the birth of a child (cells are then frozen and stored in a central facility), from peripheral (circulating) blood, or in the bone marrow (spongy material inside large bones).

In addition to restoring low levels of a patient’s stem cells following therapy, donor stem cells also attack the patient’s cancer cells. Unfortunately, they may also attack a patient’s healthy tissues, a condition referred to as graft-versus-host-disease (GVHD). Due to the potential severity of GVHD, researchers try to use stem cell donors who are related to the patient and have “matched” proteins, a practice that reduces the risk of GVHD. Unfortunately, many patients will die from their disease while waiting for a matched donor. Researchers continue to investigate ways to reduce GVHD without compromising the effectiveness of donor stem cells.

Researchers from Japan recently conducted a clinical trial including patients with leukemia or lymphoma who underwent umbilical cord blood transplants or peripheral or bone marrow allogeneic stem cell transplants.

  • At three years mortality related to treatment was 9% for those treated with umbilical cord transplants and 13% for those treated with bone marrow or peripheral blood transplants.
  • At three years relapses occurred in 17% for those treated with umbilical cord transplants and 26% for those treated with bone marrow or peripheral blood transplants.
  • At three years cancer-free survival was 70% for those treated with umbilical cord transplants and 60% for those treated with bone marrow or peripheral blood transplants.
  • For patients who were at a standard risk of developing a recurrence, cancer-free survival at three years was 93% for those treated with umbilical cord transplants and 85% for those treated with bone marrow or peripheral blood transplants.
  • For patients who were at a high risk of developing a recurrence, cancer-free survival at three years was 56% for those treated with umbilical cord transplants, compared with 45% for those treated with bone marrow or peripheral blood transplants.
  • GVHD was less frequent after umbilical cord transplants compared with bone marrow or peripheral blood transplants.

The researchers concluded that umbilical cord transplants provide results that are comparable to or better than those achieved with standard allogeneic stem cell transplants utilizing peripheral blood or bone marrow stem cells from a related donor. These results provide additional evidence that the use of umbilical cord stem cells may be an effective alternative to an allogeneic stem cell transplant from an unrelated donor.

Reference: Takahashi S, Ooi J, Tomonari A, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood. 2007;109:1322-1330.

There are several different types of hematologic malignancies, many of which are treated with a stem cell transplant.One type of stem cell transplant, an allogeneic stem cell transplant, involves the use of high-dose therapy to kill more cancer cells than standard doses. Unfortunately, the higher doses tend to destroy important hematopoietic stem cells (immature blood cells). These stem cells mature into red blood cells, which transport oxygen and nutrients to tissues in the body; white blood cells, which help the body fight infection; and platelets, which aid the blood in clotting.Low levels of hematopoietic stem cells caused by high-dose treatment can result in life-threatening conditions. In an effort to prevent this condition, donor hematopoietic stem cells are infused into the patient following therapy. Hematopoietic stem cells may be obtained from umbilical cord blood immediately following the birth of a child (cells are then frozen and stored in a central facility), from peripheral (circulating) blood, or in the bone marrow (spongy material inside large bones).In addition to restoring low levels of a patient’s stem cells following therapy, donor stem cells also attack the patient’s cancer cells.

Unfortunately, they may also attack a patient’s healthy tissues, a condition referred to as graft-versus-host-disease (GVHD). Research continues into ways to reduce GVHD without compromising the effectiveness of donor stem cells.Researchers from Japan recently analyzed data on outcomes of allogeneic stem cell transplants in which stem cells from different sources were used. This trial included 163 adults with hematologic malignancies who received stem cells from either cord blood from an unrelated donor or peripheral blood or bone marrow from a related donor. All transplants occurred between 1997 and 2005. Outcomes are as follows:

  • Treatment-related mortality at 1 year was 9% in those who received a cord blood transplant and 13% for those who received either peripheral blood or bone marrow transplant.
  • The rate of cancer relapse at 3 years was 18% for those who received a cord blood transplant, compared with 26% for those who received either peripheral blood or bone marrow transplant.
  • The rate of disease-free survival at 3 years was 71% for those who received a cord blood transplant, compared with 60% for those who received either a peripheral or bone marrow stem cell transplant.

The researchers concluded that stem cells from umbilical cord sources, even in unrelated donors, provide similar, if not superior results to stem cells derived from peripheral blood or bone marrow for the treatment of hematologic malignancies. Another advantage of stem cells from cord blood is that patients do not have to wait as long to undergo their transplant-this allows their cancer to be treated earlier. Further trials to continue evaluating the most appropriate use of cord blood in allogeneic stem cell transplants are ongoing.Patients who are to undergo an allogeneic stem cell transplant may wish to speak with their physician regarding their individual risks or benefits of the use of umbilical cord stem cells versus peripheral or bone marrow sources.

Reference: Takahashi S, Ooi J, Tomonari A, et al. Clinical Outcomes of Cord Blood Transplantation from Unrelated Donors Comparable with Marrow or Blood Transplantation from Related Donors in Adults: A Single Institute Analysis. Proceedings of the 47th annual meeting of the American Society of Hematology. Atlanta, Georgia. December 10-13, 2005.

Umbilical Cord Transplant May Be Effective Treatment Option for Some Patients with Myelodysplastic Syndromes

According to a recent article published in the journal Blood, an umbilical cord transplant may be an effective treatment option for patients with myelodysplastic syndrome that are not able to find a suitable donor for an allogeneic stem cell transplant.

Cancers are often treated with high doses of chemotherapy and/or radiation followed by a stem cell transplant. Although high-doses of therapy are more effective at killing cancer cells, many other cells in the body are also destroyed by the treatment procedure, including stem cells. Stem cells are immature blood cells produced in the bone marrow which mature into either red blood cells, white blood cells, or platelets. A stem cell transplant is a procedure that replaces the stem cells that are destroyed by high-dose chemotherapy and/or radiation therapy with healthy stem cells. In the case of an allogeneic stem cell transplant, stem cells are collected from the blood or bone marrow of a related or unrelated donor and infused into the patient after high-dose chemotherapy or chemotherapy plus total body irradiation. In addition to the anti-cancer effect of the high-dose therapy, an allogeneic stem cell transplant induces a second anti-cancer effect called the graft-versus-leukemia effect. This effect occurs after a transplant, whereby the presence of the foreign donor stem cells (ie, the graft) attacks the remaining cancer cells. However, the donor lymphocytes may also attack the patient’s healthy tissues, causing what is called graft-versus-host disease (GVHD). GVHD can be an acute or chronic disease and occurs in the majority of patients receiving allogeneic transplants.

In an effort to prevent or reduce GVHD, attempts are made to match 6 different proteins (HLA) found on stem cells between donors and patients. Many patients that could be cured with an allogeneic stem cell transplant do not have an appropriate stem cell donor. Over the past decade, researchers have learned that umbilical cord blood is a rich source of stem cells. Umbilical cord blood stem cells have been used to support high-dose chemotherapy treatment of infants and children. Now, there is a peaking interest in the use of umbilical cord blood as a source of stem cells for adult cancer patients who undergo allogeneic stem cell transplant. Recently, there has been a concerted government-funded effort to establish umbilical cord “banks” where umbilical cord blood is frozen and stored. These “banks” are now being integrated nationally and internationally with registries allowing patients to search for a stem cell donor. Thus, if a patient is unable to find a related donor, a search can be performed for an appropriate umbilical cord blood source of stem cells in various banks around the world.

The major disadvantage of using umbilical cord blood is the low number of stem cells collected. The lack of adequate numbers of stem cells in umbilical cord blood units has limited the use of this source of stem cells in adult patients, especially large adults who require more stem cells. Methods through which to expand the number of collected stem cells through laboratory processes are currently under investigation.

Researchers from Japan recently conducted a clinical trial to evaluate the effectiveness of umbilical cord transplants in 12 patients with advanced MDS. These patients were eligble for an allogeneic stem cell transplant, but an appropriate donor could not be found. Two years following therapy, 76% of patients were alive and cancer-free. Acute GVHD occurred in 75% of patients and chronic GVHD occurred in approximately 73% of patients.

The Researchers concluded that umbilical stem cell sources should be offered to patients with MDS who are eligible for an allogeneic stem cell transplant but are not able to find a suitable donor. Patients with MDS who are considering an allogeneic stem cell transplant but cannot find a donor may wish to speak with their physician about the risks and benefits of an umbilical cord transplant or the participation in a clinical trial evaluating this or other therapeutic options.

Reference: Ooi J, Iseki T, Takahashi S, et al. Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. Blood. Prepublished online February 23, 2003. Available at: http://www.bloodjournal.org/cgi/reprint/2002-12-3917v1.pdf. Accessed March 3, 2003.

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