Stem Cell Transplant for Hematological Malignancy

The purpose of this study is to develop a standard of care treatment using allogeneic stem cells for patients with cancers of the blood. The protocol was revised to reflect that this study is considered "treatment guidelines", rather than a research study.

Preparative regimen using total body irradiation (TBI) and cyclophosphamide: on day -6 and -5: cyclophosphamide is given, on day -4, -3, -2, and -1: TBI is given, on day 0: stem cell or bone marrow is infused. Alternate preparative therapy for patients not able to receive TBI The chemotherapy (cyclophosphamide and busulfan) is given with the intent of destroying the bone marrow, eliminating any cancerous and preparing for the transplant of the donor's blood stem cells by suppressing the immune system. l. Ten days before the transplant (Day 10), subjects will be admitted to the bone marrow transplant unit and placed in isolation to reduce exposure to infections. Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. 2. On day -9, -8, -7, -6 busulfan is given. 3. On day -5, -4, -3, -2 cyclophosphamide is given. 4. On day -1 no therapy is given (day of rest). 5. On day 0 the donor stem cells are given intravenously. Additional cells may be given on day +1 or 2 as needed. Transplant: Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents. During this time, they will receive the preparative treatment outlined above. Once they have received the preparative regimen, stem cells will be obtained from the donor and given intravenously. The new stem cells will replace the bone marrow that was damaged by the treatment for the cancer. Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will then be transferred from the bone marrow transplant unit and discharged from the hospital when medically ready. Subjects will be expected to return for follow-up to the bone marrow transplant clinic at specific dates as determined by their physician.

Leukemia, Myeloid, Chronic, AML, Leukemia, Lymphocytic, Acute, MDS, Leukemia, Lymphocytic, Chronic, JMML, Hodgkin's Disease, Non-hodgkin's Lymphoma, Multiple Myeloma

Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Peripheral Blood Stem Cells (PBSC) as a source of transplant

Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Bone Marrow as a source of stem cell transplant

Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Umbilical Cord Blood (UCB) as a source of stem cell transplant

Patients who receives Umbilical Cord Blood (UCB) as a source of transplant and who have not had chemotherapy in the prior 3 months receives ATG in addition to cyclophosphamide, Busulfan preparative regimen

Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Peripheral blood stem cells as a source of transplant

Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Bone Marrow as a source of stem cell transplant

Patients receiving cyclophosphamide, Total Body Irradiation (TBI), and Umbilical Cord Blood (UCB) as a source of stem cell transplant

Patients receiving cyclophosphamide, Total Body Irradiation (TBI) , CD4+CD25+ and Peripheral Blood Stem Cells (PBSC) as a source of transplant. These patients are co-enrolled on the MT2004-03 trial (NCT00725062)

Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover. (Allowable sources of stem cells = related or unrelated bone marrow or peripheral blood, for Busulfan/cyclophosphamide/ATG preparative chemo only, umbilical cord blood is also permitted.)

When not receiving total body irradiation, administered Days -9 through -6, 0.8 mg/kg/dose by intravenous dosing every 6 hours.

UCB recipients who have not had chemotherapy in the preceding 3 months will also receive Equine ATG (ATGAM) 15 mg/kg IV will be administered every 12 hours for 6 doses beginning on day -3 per institutional guidelines

Disease-Free Survival is the length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. It is sometimes used as a metric to study the health of a person with a disease to try to determine how well a new treatment is working.

Disease-Free Survival is the length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. It is sometimes used as a metric to study the health of a person with a disease to try to determine how well a new treatment is working.

Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm^3 (0.5 x 10^9/L) or greater.

Acute Graft-Versus-Host Disease (aGVHD) is a severe short-term complication created by infusion of donor cells into a foreign host. Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 post transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Determine the incidence of chronic GVHD 1 year post transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

Defined as the return of disease after its apparent recovery/cessation. Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.

Defined as the return of disease after its apparent recovery/cessation. Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.

Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.

Inclusion Criteria: Donor will be <75 years of age and in good health. Recipients will be < or = 55 years, will have normal organ function (excluding bone marrow) and will have a Karnofsky activity assessment > or = 90%. Recipients with related or unrelated donor matched at the HLA A, B, DRB1 loci, or mismatched related or unrelated (if < 35 years old) at a single HLA A, B, DRB1 locus. Recipients will be eligible in one of the following disease categories Chronic myelogenous leukemia in accelerated phase or in post blast crisis second or greater chronic phase; or in chronic phase but intolerant of or resistant to tyrosine kinase inhibitors. Acute myelocytic leukemia in first or greater remission, or first, second or third relapse. Acute lymphocytic leukemia in the 2nd or greater bone marrow remission. High risk children will be transplanted in first remission if they meet criteria Myelodysplastic syndrome. Myeloproliferative Diseases - (i.e. myelofibrosis, chronic myelomonocytic leukemia (CMML)) Juvenile myelomonocytic leukemia Chronic lymphocytic leukemia Advanced non-Hodgkin's (NHL). Advanced Hodgkin's disease beyond PR2 (> CR3, > PR3). Multiple Myeloma after initial therapy. Donors and recipients signed informed consent Exclusion Criteria donors and recipients should meet the following test criteria. required for donors: anti-HIV, Hepatitis B, surface antigen, anti-HCV, CMV, HSV, EBV serologies, pre-priming. CBC, platelet count each day of apheresis, day 0 (or 1 or 2 as needed) required for recipients: anti-HIV, Hepatitis B, surface antigen, anti-HCV, CMV, HSV, EBV serologies, pre-transplant.