Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Blood Cancer, Blood Cancer, Blood Cancer, Orthopedic, Hematology, Leukemia |
| Therapuetic Areas: | Hematology, Oncology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 55 - 71 |
| Updated: | 3/24/2019 |
| Start Date: | September 29, 1997 |
| End Date: | December 28, 2016 |
Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults
Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood
cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The
ability of BMT to cure these conditions has been credited to the use of high doses of
chemotherapy, radiation therapy, and the antileukemia effect of the transplant.
Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total
body irradiation (TBI), it is a therapy associated with toxic side effects. These side
effects are often deadly and have limited BMT for use in patients under the age of 55.
In this study researchers plan to treat older patients between the ages of 55 to 75 years
with blood cell transplants taken from donors who are genetically matched relatives of the
patient. In order to decrease the toxic side effects associated with the transplant,
researchers will not use chemoradiotherapy. Instead they plan to use intensive
immunosuppressive therapy and allow the transplanted cells to take effect....
cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The
ability of BMT to cure these conditions has been credited to the use of high doses of
chemotherapy, radiation therapy, and the antileukemia effect of the transplant.
Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total
body irradiation (TBI), it is a therapy associated with toxic side effects. These side
effects are often deadly and have limited BMT for use in patients under the age of 55.
In this study researchers plan to treat older patients between the ages of 55 to 75 years
with blood cell transplants taken from donors who are genetically matched relatives of the
patient. In order to decrease the toxic side effects associated with the transplant,
researchers will not use chemoradiotherapy. Instead they plan to use intensive
immunosuppressive therapy and allow the transplanted cells to take effect....
Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured
by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to
the use of high dose chemoradiotherapy and the antileukemia effect of the graft.
The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and
total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation
in adults to those under the age of 55 years. Toxicity related mortality increases
progressively with age and although some transplant centers carry out BMT in patients up to
the age of 60 years, it is generally accepted that treatment related mortality prohibits the
use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8
positive lymphocytes with specific reactivity for the patients leukemia and a potent graft
versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after
bone marrow transplantation where a single infusion of donor lymphocytes can induce complete
remission.
In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic
disorders with an allogeneic stem cell transplant from an HLA identical sibling, using
intensive immunosuppressive regimen without myeloablation in attempts to decrease the
transplant related toxicity while preserving the antileukemia effect of the graft. The low
intensity nonmyeloablative conditioning regimen will 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 immune reconstitution. We will add back lymphocytes in
patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of
acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to
the use of high dose chemoradiotherapy and the antileukemia effect of the graft.
The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and
total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation
in adults to those under the age of 55 years. Toxicity related mortality increases
progressively with age and although some transplant centers carry out BMT in patients up to
the age of 60 years, it is generally accepted that treatment related mortality prohibits the
use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8
positive lymphocytes with specific reactivity for the patients leukemia and a potent graft
versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after
bone marrow transplantation where a single infusion of donor lymphocytes can induce complete
remission.
In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic
disorders with an allogeneic stem cell transplant from an HLA identical sibling, using
intensive immunosuppressive regimen without myeloablation in attempts to decrease the
transplant related toxicity while preserving the antileukemia effect of the graft. The low
intensity nonmyeloablative conditioning regimen will 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 immune reconstitution. We will add back lymphocytes in
patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of
acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
- INCLUSION CRITERIA - PATIENT:
Ages 55-71 years.
Chronic myelogenous leukemia (CML): chronic phase.
Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.
Acute myelogenous leukemia (AML): AML in first complete or partial remission. Exceptions:
AML with good risk karyotypes: AML M3 t(5;17), AML M4Eo (inv. 16), AML t(8;21). All AML in
second or subsequent complete remission.
Myelodyplastic syndromes: refractory anemia with excess of blasts (less than 10%) or early
transformation to acute leukemia or Chronic myelomonocytic leukemia.
Chronic lymphocytic leukemia (CLL) with bulky or progressive disease despite prior
treatment with chemotherapy which includes purine analogs.
Mantle cell lymphoma.
Relapsed or progressive non-Hodgkins lymphoma, failing standard treatment approaches and
unsuitable for autologous stem cell transplantation.
No major organ dysfunction precluding transplantation.
DLCO greater than or equal to 40% predicted.
Left ventricular ejection fraction: greater than 30% predicted.
ECOG performance status of 0-2.
INCLUSION CRITERIA - DONOR:
HLA identical family donor, up to 75 years old.
Fit to receive G-CSF and give peripheral blood stem cells (normal blood count,
normotensive, no history of stroke, no history of severe heart disease).
Informed consent given.
EXCLUSION CRITERIA:
Patient or donor pregnant or lactating.
Patient age less than 55, greater than 71 years.
ECOG performance status of 3 or more. Psychiatric disorder or mental deficiency of the
patient or the donor sufficiently severe as to make compliance with the BMT treatment
unlikely, and making informed consent impossible.
Major anticipated illness or organ failure incompatible with survival from BMT.
DLCO less than 40% predicted.
Left ventricular ejection fraction less than 30% predicted.
Serum creatinine greater than 2.5 mg/dl.
Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of
normal.
HIV positive (donor or recipient). Donors who are positive for HBV, HCV, or HTLV will be
used at the discretion of the investigator.
Other malignant diseases liable to relapse or progress within 5 years.
Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of
heart failure or unstable angina, platelet count less than 90,000/cu mm).
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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