Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers 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.
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.
-  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).