Advertisement

Topics

Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous Leukemia

2014-08-27 03:59:46 | BioPortfolio

Summary

This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic myelogenous leukemia (CML).

Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) is a very effective treatment for CML. However, despite its success in a large number of patients, there is still a significant risk of death from the procedure. In addition, it results in sterility and leaves patients at increased risk for other cancers and for eye cataracts. These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells. In this study, radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure.

Patients with CML will be tested for matching with a donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, and others) to determine eligibility for the study. Participants will then undergo apheresis to collect lymphocytes (white blood cells important in the immune system). In apheresis, whole blood is drawn through a needle in the arm, similar to donating a unit of blood. The required component-in this case, lymphocytes-are separated and removed, and the rest of the blood is returned through a needle in the other arm.

Each day starting five days before the transplant, the donor will be given an injection of G-CSF, a drug that releases stem cells from the bone marrow into the blood stream. The cells will be collected after the fifth injection and again after a sixth injection the following day. Meanwhile, patients will be given cyclophosphamide and fludarabine, and perhaps anti-thymocyte globulin, to prevent rejection of the donated cells.

On the day of the transplant, patients will be given cyclosporin to prevent graft-versus-host-disease, a disease in which the donor cells react against the patient's cells. They may also be given lymphocytes after the transplant to boost the immune system and destroy leukemia cells. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests at least weekly for 3 months and then periodically for 5 years.

Description

CML is a disease which progresses to blast crisis within five years of onset despite medical intervention. Allogeneic transplantation has provided a definitive cure for a large number of patients. The International Bone Marrow transplant registry reports a 67% three-year disease free survival for CML patients receiving a matched sibling transplant. However there remains a 17-20% treatment-related mortality and significant long-term complications. Myeloablative regimens with total body irradiation (TBI) are associated with certain sterility, along with a significant incidence of cataracts and second malignancies. Efforts to ameliorate this toxicity have led to the development of regimens lacking total body irradiation. Although the follow-up period for patients receiving these regimens has not been long enough to answer the question of long-term toxicity, it appears that the response rate and the disease free survival are comparable to regimens containing TBI. In addition, transplantation experience with aplastic anemia where TBI is not part of the regimen indicates that treatment related mortality along with the risk of long-term sequela are significantly decreased.

Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated in phase I/II trials assessing engraftment efficacy and toxicity at a number of transplant centers. Preliminary data, including our own experience with 30 patients undergoing this type of procedure, has shown a high rate of complete donor engraftment with a low toxicity profile. Two recent studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant-related complications and mortality.

In this protocol we investigate non-myeloablative allogeneic PBSC transplantation in patients with CML. The patient group under study would include all patients with chronic phase CML having an HLA-identical sibling. In this protocol, eligible patients would be treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will add back lymphocytes in patients with less than 100% donor T-cell chimerism in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect.

The primary endpoint of this study is transplant related mortality (1 year survival). Other end points include engraftment, degree of donor-host chimerism, incidence of acute and chronic graft versus host disease (GVHD), transplant related morbidity, as well as disease-free and overall survival.

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Conditions

Chronic Myeloid Leukemia

Intervention

Modified bone marrow stem cell transplantation

Location

National Heart, Lung and Blood Institute (NHLBI)
Bethesda
Maryland
United States
20892

Status

Completed

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:59:46-0400

Clinical Trials [5982 Associated Clinical Trials listed on BioPortfolio]

Bone Marrow and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

RATIONALE: Bone marrow and peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. ...

Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

RATIONALE: Giving chemotherapy and colony-stimulating factors, such as G-CSF, may increase the number of stem cells in the blood. The stem cells are collected from the patient's blood and ...

Captopril in Treating Patients Undergoing Bone Marrow or Stem Cell Transplantation

RATIONALE: Captopril may protect the lungs from the side effects of bone marrow or stem cell transplantation. PURPOSE: Randomized phase III trial to determine the effectiveness of captopr...

Autologous Bone Marrow Mesenchymal Stem Cell Transplantation for Chronic Ischemic Stroke

Stroke is a frequently occurring and common diseases in nervous system,and most of the survivors will remain disorders of motor,sensory and cognition function.Stem cell transplantation pro...

Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell tran...

PubMed Articles [31111 Associated PubMed Articles listed on BioPortfolio]

Impact of pretransplant leukemic blast% in bone marrow and peripheral blood on transplantation outcomes of patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation in non-CR.

CC-486 Maintenance After Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes.

Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve p...

Dynamics of lymphocyte reconstitution following hematopoietic transplantation during chronic LCMV infection.

Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of cured a HIV infection involved the use of this clinical procedure, highlighting the potential ...

Saving Stem Cells after Stress.

Inflammatory signals can activate hematopoietic stem cells (HSCs), but how HSCs regain quiescence after stress is unclear. In this issue of Cell Stem Cell, Chen et al. (2017) delineate an elegant his...

Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy.

The secretome produced by cells within the bone marrow is significant to homeostasis. The bone marrow, a well-studied organ, has multiple niches with distinct roles for supporting stem cell functions....

Medical and Biotech [MESH] Definitions

Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.

The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.

Agents that destroy bone marrow activity. They are used to prepare patients for BONE MARROW TRANSPLANTATION or STEM CELL TRANSPLANTATION.

Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.

Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.

More From BioPortfolio on "Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous Leukemia"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topic

Transplantation
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...


Searches Linking to this Trial