Infections

All Conditions

Neoplasms

Blood and Lymph Conditions

Symptoms and General Pathology

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Communicable Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Acquired Immunodeficiency Syndrome

HIV Infections

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Graft vs Host Disease

HIV Seropositivity

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Homologous Wasting Disease

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

GCSF Mobilized Allogeneic PBSC Cultured w/Cytokines; Transduced w/RV

This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients.

HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure. This study uses a modified procedure, transplanting stem cells instead of bone marrow, designed to be less dangerous for such patients. Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection. The procedure in this study differs from standard bone marrow transplantation in three ways:

Stem cells will be transplanted instead of bone marrow. (Stem cells, which are produced by the bone marrow, mature into the different blood components-white and red cells and platelets.) The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream. The cells will then be collected from the donor by apheresis, a procedure in which whole blood is drawn, the stem cells separated and removed, and the rest of the blood returned to the donor.);

The procedure will use lower doses of chemotherapy than the conventional method, and will not use radiation therapy; or

A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells, rendering future cells that develop from resistance to the virus.

Prospective patients will be tested for matching with an HIV-negative donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, etc.) to determine eligibility for the study. Study participants will then undergo apheresis to collect white blood cells called lymphocytes. Stem cells will be collected from the donor. Half the donated cells will have the HIV-resistant gene inserted; the other half will have a "control" gene inserted. Additional stem cells collected a second day will not be manipulated. All the donor cells will be frozen until transplantation.

Patients will be given drugs (cyclophosphamide, fludarabine and cyclosporin) to prevent the donated cells from being rejected and to prevent them from damaging the patient's organs. The thawed stem cells will then be infused through a vein. 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 once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years.

Adult patients with myelodysplasia, leukemia, and non-Hodgkin's lymphoma can be cured by allogeneic bone marrow transplantation (BMT). This curative effect has until now been ascribed to the intense chemoradiotherapy used to condition the recipient for transplantation. The assumption that the curative effect of allogeneic transplantation rests in the ability to deliver very high doses of chemoradiotherapy has led to the restriction of allogeneic transplantation to those recipient patients whose overall status would permit the use of such intense conditioning. As a result, HIV positivity has generally appeared as an exclusion criteria to allogeneic transplantation for hematologic malignancies. Additionally, early studies of allogeneic BMT in HIV patients suggested no benefit in controlling the progression to AIDS.

Several in vitro studies have demonstrated the existence of donor derived CD4 and CD8 positive lymphocytes with specific reactivity to recipient leukemia providing a potent graft versus leukemia (GVL) effect, and this GVL effect is area of intense interest both at the NIH and elsewhere. In fact, early attempts to decrease treatment related mortality in chronic myelogenous leukemia (CML) patients undergoing allogeneic BMT by T-cell depletion of the graft resulted in an unacceptably high rate of relapse suggesting that alloreactivity in the donor graft accounted for a significant portion of the cure rate in this disease. This GVL effect is most dramatically demonstrated among relapsed allogeneic bone marrow transplant recipients transplanted for CML in whom a simple infusion of donor lymphocytes can induce a complete and durable remission.

Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being investigated for engraftment efficacy and toxicity in a number of transplant centers. Preliminary data including our own experience with 13 patients undergoing this type of procedure have shown a high rate of complete donor engraftment, low toxicity, and preservation of the GVL effect. Two recent published studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant related complications and mortality.

The decreased risk of transplant related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates and may allow successful application in patients infected with HIV. In this study, we will assess the safety and efficacy of nonmyeloablative transplantation in patients with HIV infection. Moreover, the introduction of an HIV resistance vector into a portion of the allogeneic graft provides a unique opportunity to test the in vivo efficacy of introducing resistance to HIV through the self renewing stem cell.

The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality, disease free survival, as well as overall survival, and overall level and persistence of progeny of gene modified cells.

Stem Cell (Modified Bone Marrow) Transplantation in HIV-Infected Patients With Blood Cancer

Low Intensity Non-Myeloablative Preparative Conditioning Followed by Transplantation of Genetically Modified HLA-Matched Peripheral Blood Hematopoietic Precursor Cells (PBPC) for Hematologic Malignancies in HIV Positive Adults

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lymphoma

Neoplasms by Histologic Type

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Myeloproliferative Disorders

Allogeneic bone marrow transplantation (BMT) is a curative treatment for patients with chronic myelogenous leukemia (CML) and other lymphoid/hematologic malignancies but is available as a treatment option to only a minority of patients. Autologous BMT, coupled with high dose chemotherapy, is a treatment open to more patients and is a promising strategy for the treatment of advanced solid malignancies. However, the development of potentially curative marrow transplant alternatives requires an ability to provide a nonmalignant hematopoietic stem cell population. In addition, the generation of hematopoietic stem cells (HSC), and the determination of whether or not such HSC repopulate all of the cell lineage subtypes following reinfusion are critical to understanding the biology and immunological consequences of stem cell transplantation. An increased understanding of the kinetics of HSC and lymphocyte repopulation post-BMT and the identification of donor cell populations that mediate a graft versus leukemia (GVL) effect or graft versus host (GVHD) is critical to therapeutic efficacy. In order to address these currently unmet objectives, normal volunteers and volunteers with malignancies will undergo venipuncture and bone marrow aspiration with or without prior \[6,6-(2)H(2)\] or \[U-(13)C(9)\]-glucose, infusion to provide cell populations which will then be utilized for specific pre-clinical studies aimed at developing new therapeutic alternatives for patients with CML and other lymphoid/hematologic malignancies. An infusion of \[6,6-(2)H(2)\] or \[U-(13)C(9)\]-glucose prior to bone marrow and/or leukocyte harvest, in some volunteers, will allow direct examination of the genesis and biology of stem cells and leukocyte subpopulations. \[6,6-(2)H(2)\] or \[U-(13)C(9)\]-glucose, are nonradioactive, stable isotopes of glucose which will label dividing cells during the time of administration and is chemically identical to glucose, with no adverse side effects other than those known for glucose.

Allogeneic bone marrow transplantation (BMT) is a curative treatment for patients with chronic myelogenous leukemia (CML) and other lymphoid/hematologic malignancies but is available as a treatment option to only a minority of patients. Autologous BMT, coupled with high dose chemotherapy, is a treatment open to more patients and is a promising strategy for the treatment of advanced solid malignancies. However, the development of potentially curative marrow transplant alternatives requires an ability to provide a nonmalignant hematopoietic stem cell population. In addition, the generation of hematopoietic stem cells (HSC), and the determination of whether or not such HSC repopulate all of the cell lineage subtypes following reinfusion are critical to understanding the biology and immunological consequences of stem cell transplantation. An increased understanding of the kinetics of HSC and lymphocyte repopulation post-BMT and the identification of donor cell populations that mediate a graft versus leukemia (GVL) effect or graft versus host (GVHD) is critical to therapeutic efficacy. In order to address these currently unmet objectives, normal volunteers and volunteers with malignancies will undergo venipuncture and bone marrow aspiration with or without prior \[6,6-(2)H2\] or \[U-(13)C9\]-glucose, infusion to provide cell populations which will then be utilized for specific pre-clinical studies aimed at developing new therapeutic alternatives for patients with CML and other lymphoid/hematologic malignancies. An infusion of \[6,6-(2)H2\] or \[U-(13)C9\]-glucose prior to bone marrow and/or leukocyte harvest, in some volunteers, will allow direct examination of the genesis and biology of stem cells and leukocyte subpopulations. \[6,6-(2)H2\] or \[U-(13)C9\]-glucose, are nonradioactive, stable isotopes of glucose which will label dividing cells during the time of administration and is chemically identical to glucose, with no adverse side effects other than those known for glucose.

The Collection of Peripheral Blood Lymphocytes and Marrow Progenitor Cells From Normal Volunteers and Volunteers With Lymphoid or Hematologic Malignancies

National Cancer Institute (NCI)

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Preleukemia

Myelodysplastic Syndromes

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Precancerous Conditions

Lymphatic Diseases

Leukemia, B-Cell

Anti-Infective Agents

Dermatologic Agents

Cyclosporine

Cyclosporins

Isolex 300i plus MoAbs

A. John Barrett, M.D.

Cancers of the blood, sometimes referred to as hematologic malignancies, are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow. These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms. The disease is life threatening because it blocks the normal function of the marrow, which is to produce red cells (preventing anemia), white cells (preventing infection), and platelets (preventing progression).

Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies. However, BMT is a complicated procedure and can be associated with dangerous side effects.

In this study researchers are attempting to find ways to reduce the complications of BMT, so that it would be possible to use it more safely and can be offered more patients. In order to do this, researchers are developing new techniques to make BMT safer. It requires making small changes to the standard procedure, which may improve the outcome.

The experimental procedures researchers are evaluating are:

1. \<TAB\>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation
2. \<TAB\> Cyclosporine given immediately after the transplant
3. \<TAB\>Add-back of donor lymphocytes

Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur. Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies.

Bone marrow stem cell transplant studies carried out by the NHLBI BMT Unit have focused on approaches to optimize the stem cell and lymphocyte dose in order to improve transplant survival and increase the graft-vs.-leukemia effect. A CD34 stem cell dose of greater than 3 x 10(6)/kg was found to increase survival and reduce relapse, while a CD3+ lymphocyte dose of less than 1 x 10(5)/kg was associated with a very low incidence of GVHD. Although processing of 2 peripheral blood progenitor cell (PBPC) collections with the CellPro immunoabsorption method (combined CD34-positive selection and CD2-negative selection) provided an improvement over previous methods, the system did not always achieve these optimal cell doses. A recent preclinical evaluation by the Department of Transfusion Medicine of a new immunomagnetic cell selection system available from Nexell, Inc. has demonstrated improved recovery of CD34+ cells and increased depletion of T lymphocytes, compared to the CellPro method. Incorporation of the Nexell system (Isolex 300i) into this clinical protocol will allow us to more consistently achieve CD34+ cell doses above the threshold of 3 x 10(6)/kg and CD3+ lymphocyte dosing in the region of 0.5 x 10(5)/kg. This will make it possible to test (1) the potential benefit of optimized transplant cell doses, (2) elimination of post transplant immunosuppression to enhance immune recovery.

In this study, we will use the Nexell Isolex 300i system to obtain more data on the relationship between CD34+ stem cell dose and outcome. In recipients who receive a T cell dose less than 0.5 x 10(5) CD3+ cells/kg the effect of withdrawing cyclosporine on development of GVHD will be evaluated in a cohort study: 20 patients will receive low dose cyclosporine. If the incidence of grade II or worse GVHD is 10% or less, no post transplant immunosuppression will be given to the next cohort and the incidence and severity of acute GVHD again assessed. Stopping rules for unacceptable GVHD severity will be applied. Two match groups HLA 6/6 and 5/6 donor-recipient pairs will be separately studied using this approach.

In a second phase of the study we will continue to accumulate data on T lymphocyte add-back given on day 45 and day 100 after transplant. For this phase, cyclosporine will be reintroduced on day 44 and continued until day 120 to accelerate immune recovery.

Up to 70 patients aged between 10 and 55 years will be studied in each subset (HLA 6/6 and 5/6 matched cohorts). The major endpoint of the study is acute GVHD after transplant. We will also measure engraftment, acute and chronic GVHD, leukemic relapse, transplant-related and all causes of mortality, cytomegalovirus reactivation and leukemia-free survival. Patients will be followed for a minimum of 5 years.

The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers

Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies - Role of Cyclosporine

National Heart, Lung, and Blood Institute (NHLBI)

Thromboembolism

Venous Thromboembolism

Thrombosis

Embolism

Embolism and Thrombosis

Observation

Valerio De Stefano

The primary objective of the study is to assess efficacy and safety of different prophylactic or therapeutic antithrombotic approaches in patients with hematologic neoplasms and platelet count \<50 x109/L, including unfractionated or low molecular weight heparin, fondaparinux, anti-vitamin K agents, antiplatelet agents, novel oral anticoagulants, fibrinolytic agents, with or without a policy of platelet transfusion. Cases with arterial or venous thromboembolism managed with observation or use of vena cava filters in patients with venous thromboembolism will be included too.

Illness treatment overview The incidence of venous thromboembolism (VTE) among patients with haematological malignancies has been recently reviewed (1). For patients with lymphoma, the incidence of VTE ranged from 1.5 to 14.6% and is 59% in patients with central nervous system lymphoma. The incidence of VTE in patients with acute leukaemia varies with time, being between 1.4 and 9.6% at diagnosis and between 1.7 and 12% during induction therapy. Notably, the highest rates of VTE were reported in patients with acute promyelocytic leukaemia, with values between 6 and 16% in the largest series. In patients with multiple myeloma who did not receive antithrombotic prophylaxis, the rate of VTE increased to 26% in those undergoing treatment regimens including immumodulatory drugs (thalidomide and lenalidomide) (1). Moreover, in patients who have undergone autologous or allogeneic haematopoietic stem cell transplantation (HSCT), the rate of VTE is between 2.9 to 9.9%, and was central venous catheter (CVC)-associated in the majority of cases (2-4). VTE has been shown to occur even during periods of severe thrombocytopenia; one-third of the events from a patient series occurred when the platelet count was \<50 x109/L (3). Patients with acute leukaemia have a high risk of haemorrhage, mostly related to thrombocytopenia as a result of haematological disease and/or chemotherapy, such that the administration of anticoagulant drugs in this setting is problematic. No randomised controlled trials have addressed the issue of VTE treatment in patients with acute leukaemia, and the management of these cases is based only on small groups of patient series or experts' opinion. Five reports have described in detail cases of paediatric or adult patients with malignancies and thrombocytopenia who have been treated with heparin as a result of a VTE (5-9). Out of a total of 54 cases, 32 had haematological malignancies and a platelet nadir \<50 x109/L (reviewed in ref. 10). The majority of patients (22 of 32) had CVC-related thrombosis. A full dose of low molecular weight heparin (LMWH) bid was administered to the majority of the patients with CVC-related thrombosis and to the totality of patients for whom the thrombosis was not CVC-related. All patients received platelet transfusions if the platelet count fell below \<20-40 x109/L, and the dose of LMWH was halved when the platelet count was \<20 x109/L in one report. None of the patients had major bleeding. Rethrombosis occurred in three of 32 (9.3%) patients (6,7). In a large series of 379 patients with acute leukaemia, treatment for 20 patients who had one (n=16) or two (n= 4) VTE events was essentially based on the administration of enoxaparin 100 U/kg bid; in the case of a platelet count \<50 x109/L or in the clinical suspicion of bleeding risk the dose was reduced to 100 U/kg qd or 50 U/kg bid. Alternatively, the patients received a continuous i.v. infusion of unfractionated heparin (UFH) to obtain aPTTs in the lower therapeutic range (1.5 times greater than the basal value). Secondary prophylaxis after acute VTE was based on the administration of enoxaparin 100 U/kg qd in the case of ongoing chemotherapy or vitamin K-antagonists (VKA) (INR between 2 and 3) otherwise. In general, the length of secondary prophylaxis was reported to be not longer than six months (11). The safety of therapeutic anticoagulation treatment for the management of thrombocytopenic patients was also evaluated in two series of patients receiving HSCT (12,13). In 10 patients with multiple myeloma who had received autologous HSCT, anticoagulation was required following pre-transplant CVC-related subclavian vein thrombosis (n= 8), pulmonary embolism two months prior to transplant (n= 1), or a history of acute intermittent atrial fibrillation that was complicated by an arterial embolus to the leg (n= 1). Beginning on the first day of high-dose chemotherapy, the 10 patients received therapeutic UFH (a 5,000 U i.v. bolus followed by 1,000 U per h) to maintain aPTTs between 50 and 70 seconds and were switched to VKA treatment when their conditions stabilised. UFH treatment was interrupted once the VKA administration produced a therapeutic INR \>2 for two consecutive days. Heparinised patients received platelet transfusions to maintain counts \>30 x109/L. Three patients developed bleeding (haematuria, haematemesis, mucosal bleeding) that did not not require transfusion, and no thrombotic events occurred (12). In another series of 26 patients with HSCT who were given enoxaparin for the treatment of VTE, 21 patients had haematological malignancies. There were 25 VTE events recorded (four patients had two events at different sites) and 11 cases had upper extremity CVC-related deep venous thrombosis. During periods of thrombocytopenia (\<55 x109/L), enoxaparin administration was reduced to a median value of 49 U/kg/day (range 34-75) and was withdrawn in some instances when the platelet count fell below 20 x109/L. Two major bleeding events (8%) occurred, in one case fatal (13). The aforementioned data are insufficient for the production of evidence-based guidelines. Experts and the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) have suggested that the first two weeks of treatment should consist of the administration of full-dose LMWH (anti-factor Xa level 0.5-1 U/ml), maintaining the platelet count above 50 x109/L. After the first two weeks, halving the dose is recommended if the platelet count is between 20 and 50 x109/L. If the platelet count is below 20 x109/L, it is advised that the LMWH therapy be discontinued until the platelet count recovers to greater than 20 x109/L (14-16). Recent guidelines of the SISET (Società Italiana per lo Studio dell'Emostasi e della Trombosi) also suggested that in patients with haematological malignancies and VTE LMWH should be preferred over VKA either for the first six months or a longer time (17). Arterial thrombosis has been rarely reported in patients with acute leukemia as heralding manifestation or complicating the course of disease (18-21). However, details concerning antithrombotic treatment and the platelet count at the time of the event are lacking in the majority of the reported cases. There have been no published studies concerning the use of novel antithrombotic agents such fondaparinux, direct thrombin or factor Xa inhibitors, in patients with haematological malignancies or thrombocytopaenia. However, in vitro experiments that have been performed on plasma from children with ALL and antithrombin deficiency as a result of the administration of asparaginase have demonstrated that the direct thrombin inhibitor melagatran generates a consistent anticoagulant response that is independent of the antithrombin level. Therefore, this drug class may have important potential for use in this field (22).

Rationale Data about treatment of arterial or venous thromboembolism in patients with haematological malignancies and thrombocytopenia are mainly anecdotal. The very limited knowledge in this setting does not allow to plan a randomized controlled trial, lacking a standard of care and being quite uncertain the benefits and risks of different strategies. Therefore we planned an observational study either retrospective and prospective to gain information about efficacy and safety of different therapeutic strategies in patients with hematologic neoplasms and platelet count \<50 x109/L having had diagnosis of arterial or venous thromboembolism.

PENELOPE Observational Study: Prophylaxis and Treatment of Arterial and Venous Thromboembolism

Clinical Practice in the Prophylaxis and Treatment of Arterial and Venous Thromboembolism in Patients With hEmatological NEoplasms and LOw PlatElets (PENELOPE Observational Study)

In patients with hematologic neoplasms and platelet count \<50 x109/L having had diagnosis of arterial or venous thromboembolism and undergoing different therapeutic approaches the following events will be recorded:

* Progression of thrombosis during 3 months from diagnosis;
* Novel thrombotic events in other sites during 3 months from diagnosis;
* Major bleeding during 3 months from diagnosis;
* Fatal thrombosis or bleeding;
* Non-vascular death.

In patients with hematologic neoplasms and platelet count \<50 x109/L undergoing antithrombotic prophylaxis the following events will be recorded:

* Thrombotic events during 3 months from the start of prophylaxis;
* Major bleeding during 3 months from the start of prophylaxis;
* Fatal thrombosis or bleeding;
* Non-vascular death.

Gruppo Italiano Malattie EMatologiche dell'Adulto

Allogeneic Bone Marrow Transplant

Bone marrow transplants (BMT) are one of the accepted therapies used to treat leukemia. However, BMT have risks of complications. One potentially life-threatening complication is known as graft-versus-host disease (GVHD).

The GVHD is a reaction caused by an incompatibility between donor cells and recipient cells. Antigens found on the recipient s cells are recognized by the donor s transplanted white blood cell lymphocytes. These lymphocytes begin attacking the recipient s cells and tissues and may lead to death.

One of the most effective ways to prevent this reaction is to remove the lymphocytes from the transplanted marrow. Unfortunately, without lymphocytes the recipient s immune system will be lowered and may result in a relapse of leukemia or an infection.

Researchers have shown they can perform effective BMT by removing the lymphocytes prior to the transplant and then later adding the lymphocytes back. This technique can reduce the potential for GVHD and preserve the graft-versus-leukemia (GVL) effect of the transplant.

In this study researchers plan to use peripheral blood with lymphocytes removed rather than bone marrow. In order to increase the number of progenitor cells, the cells responsible for correcting the leukemia, donors will receive doses of G-CSF prior to the transplant. G-CSF (granulocyte colony stimulating factor) is a growth factor that increases the production of progenitor cells in the donor s blood stream.

The study will be broken into two parts. The first part of the study will attempt to determine if peripheral blood with lymphocytes removed can prevent GVHD while preserving the GVL effect of the transplant.

In the second part of the study, patients that received the transplant will have the lymphocytes added-back on two separate occasions in order reduce the chances of relapse and infection.

The study is designed to treat up to 55 patients ages 10 to 60 years and follow their progress for 5 years.

One of the most effective ways of preventing lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) for leukemia is to remove T-lymphocytes from the transplanted marrow. The reduced early mortality from T cell depletion is however offset by an increased risk of leukemic relapse and infection. We have shown that bone marrow transplants for leukemia depleted of T cells by elutriation and followed by delayed add-back of donor T cells reduces GVHD while preserving an immune response to the hematologic malignancy (the so-called graft-versus-leukemia (GVL) or graft-versus-myeloma effect). The study highlighted a possible benefit of large doses of marrow progenitor cells on transplant outcome. GVHD was reduced but not prevented by T cell depletion of the marrow. The first objective of our BMT studies is to prevent GVHD from the transplant while conserving GVL reactivity. This is a prerequisite to our second objective of determining the risk of GVHD and the benefit from GVL from add-back of donor lymphocytes. These studies will provide the basis for a planned trial adding back donor lymphocytes selected in vitro to confer immunity against infectious agents and residual leukemia without causing GVHD.

In this study we will evaluate the use of T cell depleted peripheral blood progenitor cells (PBPC) (instead of bone marrow) to optimize the stem cell and lymphocyte dose. Donors will be given G-CSF and their mobilized PBPC harvested by leukapheresis. To minimize acute GVHD, the transplant will be T cell depleted, using a new technique developed in normal volunteers which improves T cell depletion and reduces stem cell loss (protocol 96-H-0049). The study has two phases: The first phase evaluates engraftment and GVHD following T cell depleted PBPC transplants. Stopping rules will be used to make modifications to the protocol in the event of graft failure. Cyclosporine will be withdrawn from the protocol if the incidence of acute GVHD is low or absent. In the second phase patients will receive add-back of donor lymphocytes on day 45 and day 100 post transplant to prevent relapse and confer donor-immune function. The risk of acute GVHD following this procedure will be determined. It is planned to treat up to 55 patients aged between 10 and 60 years. The end points of the study are graft take; acute and chronic GVHD, leukemic relapse, transplant-related and all causes of mortality, cytomegalovirus reactivation and leukemia-free survival. Patients will be followed for 5 years.

Bone Marrow Transplant Studies for Safe and Effective Treatment of Leukemia

HLA-Matched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T Cell Add-Back for Hematological Malignancies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stem Cell (Modified Bone Marrow) Transplantation in HIV-Infected Patients With Blood Cancer	NCT00005785	Hematologic Neo... HIV Infection	GCSF Mobilized ...	-	National Institutes of Health Clinical Center (CC)
The Collection of Peripheral Blood Lymphocytes and Marrow Progenitor Cells From Normal Volunteers and Volunteers With Lymphoid or Hematologic Malignancies	NCT00001432	Chronic Myeloid... Healthy Hematologic Neo... Lymphoma		-	National Institutes of Health Clinical Center (CC)
The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers	NCT00001873	Chronic Lymphoc... Graft vs Host D... Hematologic Neo... Multiple Myelom... Myelodysplastic...	Isolex 300i plu...	10 Years - 55 Years	National Institutes of Health Clinical Center (CC)
PENELOPE Observational Study: Prophylaxis and Treatment of Arterial and Venous Thromboembolism	NCT01855698	Hematologic Neo... Acute Leukemia Myelodysplastic... Lymphoma Multiple Myelom...	Observation	18 Years -	Gruppo Italiano Malattie EMatologiche dell'Adulto
Bone Marrow Transplant Studies for Safe and Effective Treatment of Leukemia	NCT00001623	Graft vs Host D... Hematologic Neo... Leukemia Multiple Myelom... Myelodysplastic...	Allogeneic Bone...	10 Years - 55 Years	National Institutes of Health Clinical Center (CC)
PENELOPE Observational Study: Prophylaxis and Treatment of Arterial and Venous Thromboembolism	NCT01855698	Hematologic Neo... Acute Leukemia Myelodysplastic... Lymphoma Multiple Myelom...	Observation	18 Years -	Gruppo Italiano Malattie EMatologiche dell'Adulto

Spots Global Cancer Trial Database for hematologic neoplasm