T-Reg Cell Kinetics, Stem Cell Transplant, REGALE

Patients have a type of blood cell disorder that is very hard to cure. We are now suggesting a treatment that might help patients live longer without disease than other treatment plans would. This treatment is known as a stem cell transplant. We believe this may help patients as it allows us to give much stronger doses of drugs and radiation to kill the diseased cells than we could give without the transplant. We also think that the healthy cells may help fight any diseased cells left after the transplant. Stem Cells are special "mother" cells that are found in the bone marrow (the spongy tissue inside bones), although some are also found in the bloodstream (peripheral blood). As they grow, they become either white blood cells which fight infection, red blood cells which carry oxygen and remove waste products from the organs and tissues or platelets, which enable the blood to clot. For the transplant to take place, we will collect these stem cells from a "donor" (a person who agrees to donate these cells) and give them to recipient. Patients do not have a sibling that is a perfect match, so the stem cells will come from a donor who is the best match available. This person may be a close relative or an unrelated person whose stem cells best "matches" the patients, and who agrees to donate stem cells. Before the transplant, two very strong drugs plus total body irradiation will be given to the patient (pre-conditioning). This treatment will kill most of the blood-forming cells in the bone marrow. We will then give the patient the healthy stem cells. Once these healthy stem cells are in the bloodstream they will move to the bone marrow (graft) and begin producing blood cells that will eventually mature into healthy red blood cells, white blood cells and platelets. This research study will also use CAMPATH-1H as a pre-treatment. CAMPATH-1H is an antibody against certain types of blood cells. CAMPATH-1H is important because it stays active in the body for a long time after infusion, which means it may work longer at preventing GvHD symptoms. The stem cell transplant described above is considered to be "standard" treatment. We would like to collect additional blood as described below in order to evaluate how the immune system is recovering. We are asking permission to draw blood from the patient so that we can measure the number of certain blood cells called T regulatory cells. T regulatory cells are special immune cells that can control or regulate the body's immune response. We want to determine whether T regulatory cells are important participants in graft versus host disease (GVHD), infection and relapse. In GVHD, certain cells from the donated marrow or blood (the graft) attack the body of the transplant patient (the host). GVHD can affect many different parts of the body. The skin, eyes, stomach and intestines are affected most often. GVHD can range from mild to life-threatening. We do not know whether T regulatory cells can modify these conditions. We want to measure these T regulatory cells and learn if these cells do influence these conditions. If we learn that T regulatory cells do affect these conditions, then it may be possible to modify these cells for the benefit of transplant patients.

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All

INCLUSION CRITERIA:

* Patients with acute or chronic leukemia or advanced Hodgkin or non Hodgkin lymphoma or myelodysplastic/myeloproliferative disease who are unlikely to be cured by standard chemotherapy treatments. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostic features.
* Using the standard 6 HLA antigen profile (HLA class I, A and B, and HLA class II, DRB1) a patient must have either a one HLA antigen mismatched related donor or an HLA matched or one antigen mismatched unrelated donor.

EXCLUSION CRITERIA:

* Patients with a life expectancy (less than or equal to 6 weeks) limited by disease other than leukemia.
* Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction \<20%).
* Patients with severe renal disease (i.e., creatinine greater than 3 times normal for age).
* Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted).
* Patients with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST greater than 500 IU/L).
* Patients with severe personality disorder or mental illness.
* Patients with severe infection that in the estimation of the principal investigator prohibits the use of ablative chemotherapy.
* Patients who are documented HIV positive.
* Patients with a Karnofsky performance score \<70% or Lansky score \<50%.

NOTE: Patients who would be excluded from treatment on this protocol strictly for laboratory abnormalities can be included at the principal investigator's discretion after consultation with the members of the SCT Policy and Procedures Committee.

• DERIVEDCohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31. PMID 21454450