Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Immunologic Deficiency Syndromes

Lymphoproliferative Disorders

Myeloproliferative Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Lymphatic Diseases

Immunoproliferative Disorders

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Busulfan

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Evaluate the Pharmacokinetics of orally busulfan

Evaluate the Pharmacokinetics of intravenously busulfan

Evaluate the Bu pharmacokinetics (PK) when the drug will be received by P.O or I.V and we will establish the target "Area Under Curve- AUC" based on a single daily dose (test dose) before HSCT. The test dose of orally Bu is 1 mg/Kg and the blood samples are collected and processed in time: 0h, 30 min, 1h, 1,5h, 2h, 3h, 4h, 5h and 6h after drug intake. After extraction of the plasma samples busulfan, quantitative analyzes of busulfan on human plasma will be performed by the liquid chromatograph. For the patients that will receive intravenously busulfan, the test dose is 32 mg/m2 and blood samples are collected in time: 0h, 30', 45', 1h, 2h, 3h, 4h, 5h, 6h and 8h after drug intake. The dose during the conditioning will depend on the test dose and the AUC target.

Analyze the pharmacokinetics of busulfan for transplantation

Iracema Esteves, investigator

Sandra Nakashima, nurse

Iracema Esteves, Doctor

Sandra Saemi Nakashima, Nurse

Fabio R Kerbauy, Doctor

Nelson Hamerschlak, Doctor

The purpose of this prospective study is evaluate the best dose of busulfan for each patient undergoing Haematopoietic Stem Cell Transplantation

* Busulfan is an alkylating antineoplastic agent used commonly during the conditioning regimen in patients undergoing Haematopoietic Stem Cell Transplantation (HSCT). Due to the fact that this drug has a variable metabolism in different individuals, the investigators performed the plasmatic dosage of chemotherapy before starting the conditioning regimen (test dose) as a way to predict the best dose to them during the conditioning. Busulfan toxicities depends on the "Area Under Curve" and Concentration Steady State (CSS).
* The investigators randomized in groups according to the route of drug administration: per oral and intravenously. Dose test will be performed before conditioning and othe pharmacokinetics (Pk) study will be made in the first day of conditioning. The test dose of P.O busulfan will be 1 mg/Kg/dose and 32 mg/m2 for I.V busulfan. The target dose of busulfan during the conditioning will depends on the Pk obtained during the test dose. In the first day of regimen, other samples will be analysed and the new AUC will be adjusted. We will have a control group who have never performed monitoring before (retrospective group)
* Test Dose for oral busulfan will be performed with peripheral blood samples at the time: 0h (before taking busulfan), 30', 1h, 1,5h, 2h, 3h, 4h, 5h and 6h. In the first day of conditioning other samples will be collected again in the same moments.
* Test dose for I.V busulfan will be performed on time 0h, 30', 45', 1h, 2h, 3h, 4h, 5h, 6h and 8h after receiving I.V busulfan. If the patients will receive I.V busulfan during conditioning, the blood samples should be collected on time 0h, 30', 1h, 2h, 3h, 4h, 5h, 6h, 7h and 8h after taking busulfan. The blood samples will be centrifuged (4º C/ 3200 rpm/10 minutes) and analysed.
* Patients will be monitored with pharmacokinetic's drug and clinical outcomes. The investigators will evaluate acute and chronic toxicities after Stem Cell Transplantation.

Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation

To study the effectiveness dosing of busulfan plasma levels during the administration of orally busulfan or intravenous prior to HSCT (test dose) and correlate with the respective plasma measurements in the first days of conditioning

Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation

Evaluate 5-years cumulative incidence of relapse and non relapse mortality in patients that underwent stem cell transplantation with busulfan in conditioning regimen

Evaluate 1-year Disease Free Survival in patients that underwent stem cell transplantation with busulfan in conditioning regimen who enter complete remission after

Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen

Hospital Israelita Albert Einstein

Heart and Blood Diseases

Symptoms and General Pathology

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Anemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Anemia, Aplastic

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Chronic Disease

Disease Attributes

Bone Marrow Failure Disorders

Pancytopenia

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Aplastic Anemia

Chronic Myeloid Leukemia

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Tacrolimus

Fludarabine

Fludarabine phosphate

Methotrexate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Calcineurin Inhibitors

Folinic Acid

Folate

Vitamin B9

Day Preparative Regimen for GVHD Prophylaxis

* 7 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV
* 6 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV
* 5 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV
* 4 Busulfan 0.8 mg/kg IV Q6 hurs, Fludarabine 30 mg/m(2)IV
* 3 Fludarabine 30 mg/m(2)IV
* 2 REST Tacrolimus 0.01 mg/kg CIVI
* 1 REST 0 Unrelated Stem Cell/Bone Marrow Infusion

  * 1 Methotrexate 5mg/m(2)IV
  * 3 Methotrexate 5mg/m(2)IV
  * 6 Methotrexate 5mg/m(2)IV
  * 7 G-CSF 5mcg/kg SQ daily
  * 11 Methotrexate 5mg/m(2)IV
  * 90 Evaluate Response

Busulfan/Fludarabine phosphate/Tacrolimus/Methotrexate/G-CSF

Thomas G. Martin, M.D.

The primary objective of this study is to assess the safety and efficacy of performing unrelated stem cell transplants using intravenous busulfan and fludarabine as preparative therapy and tacrolimus plus methotrexate as the GVHD prophylaxis regimen. The goal is to demonstrate safety, aiming for a transplant related mortality rate (TRM) of \< or equal to 40% at 100 days. A TRM of \> or equal to 60% will be considered unacceptable. Another goal is to demonstrate efficacy by showing and overall survival of \>40% at 1-year following transplant.

Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT

Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation

University of California, San Francisco

Beth Davis

Infections

Skin and Connective Tissue Diseases

Communicable Diseases

Herpes Simplex

Epstein-Barr Virus Infections

Virus Diseases

Infectious Mononucleosis

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Chronic Active Epstein-Barr Virus Infection

Patients with chronic active Epstein-Barr virus.

Jeffrey I Cohen, M.D.

Epstein-Barr virus (EBV) is a member of the human herpes virus family that infects more than 95 percent of the U.S. population. Most infections occur in childhood and cause no symptoms; in adolescents and adults, EBV often causes infectious mononucleosis. It has also been associated with certain forms of cancer. Chronic Epstein-Barr virus (CAEBV) is a rare disease, primarily of children and young adults, that leads to life-threatening infections.

This study seeks to identify genetic mutations responsible for CAEBV. A secondary goal is to learn more about the natural history of CAEBV.

The study will examine blood and tissue samples from up to 50 patients (age 3 and above) with CAEBV and up to 150 of their relatives (age 1 and above). Autopsy samples may be included in the study. Up to 300 anonymous blood samples from the NIH Clinical Center Blood Transfusion Medicine will also be examined for comparison.

No more than 450 milligrams (30 tablespoons) of blood per 8 weeks will be drawn from adult patients, and no more than 7 milliliters per kilogram of blood per 8 weeks will be drawn from patients under age 18. Local health care providers will refer patients to the study and will obtain the samples. Some patients may also be seen at the NIH Clinical Center. Those patients will have a full medical history and physical examination, along with chest X-ray, blood counts, blood chemistry, EBV serologies, and viral load. Other tests, such as CT scan or MRI, may be performed if medically indicated. Patients will be asked to undergo leukapheresis.

In vitro tests on the blood or tissue samples will include analysis for proteins or genes that are involved in the immune response; cloning of portions of patient DNA; transformation of B cells with EBV; measurement of the ability of patient blood cells to kill EBV-infected cells; determination of lymphocyte subsets; and determination of antibodies to EBV or other herpes viruses.

If a genetic cause for CAEBV is found, the investigators will be available to discuss the results with patients in person or by telephone. Genetic indications of risk for other diseases will also be discussed with patients.

Patients with chronic active Epstein-Barr virus (CAEBV) have (a) an illness that began as a primary infection with EBV or markedly elevated titers of antibodies to EBV, (b) histological evidence of organ disease, and (c) elevated EBV DNA levels in the blood or EBV DNA or proteins in affected tissues. This is primarily a disease of children and young adults. Many of these patients develop hypogammaglobulinemia or pancytopenia and death is frequently due to opportunistic infections or B or T cell lymphoproliferative disease. The primary goal of this study is to identify genetic mutations responsible for CAEBV. The secondary goal of this study is to learn more about the natural history of CAEBV. Blood samples or available tissues (e.g. previous biopsy or autopsy material) from patients with CAEBV and their relatives will be analyzed to identify disease genes that are mutated in this population. In addition, some of the patients will be invited to come for evaluation at the NIH Clinical Center. At that time medically indicated studies of disease progression will be performed. Serial virologic and immunologic studies will be performed. Eligible relatives of patients will be studied to compare the gene(s) associated with CAEBV in patients with the gene(s) in their relatives. Knowledge gained from this study has the potential of providing insights into the immunologic control of EBV infections. In addition, identification of the molecular mechanisms for CAEBV may provide insights leading to improved treatments for this disease.

Genetic Studies of Chronic Active Epstein-Barr Disease

Genetic Studies of Chronic Active Epstein-Barr Virus Infection

Provide insights into the immunologic control of EBV infections.

Identification of the molecular mechanisms fro CAEBV.

National Institute of Allergy and Infectious Diseases (NIAID)

Lymphoma, Follicular

Lymphoma, Non-Hodgkin

Follicular Lymphoma

Samples obtained from patients with :

LF: Follicular lymphoma MCL: Mantle cell lymphoma CLL/SLL: chronic lymphocytic leukemia/small lymphocytic leukemia MZL : splenic marginal zone Clt :control B-cells

Background:Altered Toll-like receptor (TLR) expression levels and/or mutations in its signaling pathway (such as MyD88 mutation) contribute to the pathogenesis of lymphoproliferative disorders (LPD). CD180 is an orphan member of the TLR family that modulates the signaling of several TLRs, but only limited studies have evaluated its expression by flow cytometry (FCM) in LPD.

Methods: Using a multiparameter FCM approach, biologists have assessed CD180 mean fluorescence intensity (MFI) in lymph nodes (LNs) and peripheral blood (PB) samples obtained from patients with follicular lymphoma (FL; LN/PB, n=44/n=15), chronic lymphocytic leukemia (CLL, n=26/n=21), mantle cell lymphoma (MCL, n=13/n=17), and marginal zone lymphoma (MZL, n=16/n=12). Specimens from non-tumoral PB and LN (n=8/n=12) were used as controls.

Using a multiparameter FCM approach, biologists have assessed CD180 mean fluorescence intensity (MFI) in lymph nodes (LNs) and peripheral blood (PB) samples obtained from patients with follicular lymphoma (FL; LN/PB, n544/n515), chronic lymphocytic leukemia (CLL, n526/n521), mantle cell lymphoma (MCL, n513/n517), and marginal zone lymphoma (MZL, n516/n512). Specimens from non-tumoral PB and LN (n58/n512) were used as controls.

CD180 Overexpression in Follicular Lymphoma

CD180 Overexpression in Follicular Lymphoma Is Restricted to the Lymph Node Compartment

Using a multiparameter FCM approach, biologists assessed the CD180 expression by our routine antigen panel in LN suspensions as well as in PB samples. Samples were analyzed on a BD FACSCanto II cytometer (BD FACS DIVA software; Becton Dickinson, San Jose, CA).

Hospices Civils de Lyon

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation	NCT01800643	Acute Leukemia Chronic Leukemi... Lymphoprolifera... Myeloproliferat... Immunodeficienc...	Analyze the pha...	-	Hospital Israelita Albert Einstein
Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation	NCT01800643	Acute Leukemia Chronic Leukemi... Lymphoprolifera... Myeloproliferat... Immunodeficienc...	Analyze the pha...	-	Hospital Israelita Albert Einstein
Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT	NCT00516152	Chronic Myeloid... Acute Myelogeno... Myelodysplasia Acute Lymphocyt... Severe Aplastic... Non-Hodgkin's L... Lymphoprolifera... Multiple Myelom... Advanced Myelop...	Busulfan/Fludar...	15 Years - 61 Years	University of California, San Francisco
Genetic Studies of Chronic Active Epstein-Barr Disease	NCT00032513	Chronic Active ...		1 Year - 120 Years	National Institutes of Health Clinical Center (CC)
CD180 Overexpression in Follicular Lymphoma	NCT02978898	Follicular Lymp...		18 Years -	Hospices Civils de Lyon
Genetic Studies of Chronic Active Epstein-Barr Disease	NCT00032513	Chronic Active ...		1 Year - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for lymphoproliferative disease