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| ID | Type | Description | Link |
|---|---|---|---|
| 0207M29448 | Other Identifier | IRB, University of Minnesota |
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This study tests the clinical outcomes of a preparative regimen of fludarabine (FLU), anti-thymocyte globulin (ATG)/or Campath, and melphalan; followed by hematopoietic stem cell transplant, and a post transplant regimen of Cyclosporin A (CsA) in patients with immunologic or histiocytic disorders. The researchers hypothesize that this regimen will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease (GVHD).
Patients will be randomized biologically into one of 3 arms based upon donor availability: (a) human leukocyte antigen (HLA) genotypic matched sibling donor, (b) HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, (c) two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).
Prior to transplantation, subjects will receive Melphalan, Fludarabine and Anti-Thymocyte Globulin (ATG) or Campath. These three drugs are being given to subjects to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.
After stem cell transplantation, subjects will be given Cyclosporin A (CsA) and mycophenolate mofetil (MMF) to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 - Matched sibling donor | Active Comparator | Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG) |
|
| Arm 2 - Matched unrelated donor | Active Comparator | Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG) |
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| Arm 3 - Mismatched double cord donors | Active Comparator | Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stem Cell Transplant | Procedure | IV on Day 0 |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Mixed Chimerism | >10% Donor Cells at Day 100 | Day 100 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Donor Chimerism at 100 Days | The percent of recipient bone marrow and blood cells that are of donor origin. | Day 100 |
| Percentage of Donor Chimerism at 180 Days | The percent of recipient bone marrow and blood cells that are of donor origin. |
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Inclusion Criteria:
Patients with immunodeficiencies or histiocytic disorders 0-35 years of age with an acceptable stem cell donor and disease characteristic defined by the following:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Angela Smith, MD | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 - Matched Sibling Donor | human leukocyte antigen (HLA) genotypic matched sibling donor Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Fludarabine | Drug | 30mg/m^2 IV Day -7 through Day -3 |
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| Melphalan | Drug | 140 mg/m^2 IV Day -1 |
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| Anti-thymocyte globulin (ATG) | Drug | 30 mg/kg IV Day -5 through Day -1 |
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| Campath 1H | Drug | 0.2 mg/kg IV X 5 days (used as an alternative to Anti-thymocyte globulin (ATG) if unable to tolerate ATG) Day -10 through Day -6 |
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| Cyclosporin A | Drug | 2.5 mg/kg IV every 12 hours (adults) or every 8 hours (children <40 kg) maintaining a level of >200mg/L Day -3 until Day +180 when, if no GVHD, the dose will be tapered 10% per week beginning on day 181 |
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| Mycophenolate mofetil | Drug | 15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present |
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| Intravenous immunoglobulin (IVIG) | Drug | 500 mg/kg IV weekly beginning on Day +7 until Day +100 |
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| Day 180 |
| Percentage of Donor Chimerism at 365 Days | The percent of recipient bone marrow and blood cells that are of donor origin. | Day 365 |
| Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD) | Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease. | Day 100 |
| Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD) | Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease. | Day 100 |
| Incidence of Chronic Graft Versus Host Disease (cGVHD) | Chronic graft versus host disease (cGVHD) is a reaction which typically develops 3 to 6 months after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. | 6 months and 1 year |
| Number of Subjects Alive at 100 Days | Day 100 |
| Number of Subjects Alive at One Year | Day 365 |
| Compare Quality of Life (QOL) | Pretransplant, 1 year, 2 years and 5 years |
| Arm 2 - Matched Unrelated Donor |
HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| FG002 | Arm 3 - Mismatched Double Cord Donors | two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord). Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 - Matched Sibling Donor | human leukocyte antigen (HLA) genotypic matched sibling donor Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| BG001 | Arm 2 - Matched Unrelated Donor | HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| BG002 | Arm 3 - Mismatched Double Cord Donors | two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord). Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Mixed Chimerism | >10% Donor Cells at Day 100 | Arm 2: 2 of 10 patients not evaluable due to failure to return to clinic for the Day 100 evaluation. Arm 3: 2 of 6 patients not evaluable due to early death. | Posted | Number | participants | Day 100 |
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| Secondary | Percentage of Donor Chimerism at 100 Days | The percent of recipient bone marrow and blood cells that are of donor origin. | Arm 2: 2 of 10 patients not evaluable due to failure to return to clinic for the Day 100 evaluation. Arm 3: 2 of 6 patients not evaluable due to early death. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 100 |
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| Secondary | Percentage of Donor Chimerism at 180 Days | The percent of recipient bone marrow and blood cells that are of donor origin. | Arm 2: 2 of 10 patients not evaluable due to failure to return to clinic for the Day 100 evaluation. Arm 3: 2 of 6 patients not evaluable due to early death. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 180 |
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| Secondary | Percentage of Donor Chimerism at 365 Days | The percent of recipient bone marrow and blood cells that are of donor origin. | Arm 2: 2 of 10 patients not evaluable due to failure to return to clinic for the Day 100 evaluation. Arm 3: 2 of 6 patients not evaluable due to early death. | Posted | Mean | Standard Deviation | percentage of donor cells | Day 365 |
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| Secondary | Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD) | Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease. | Posted | Number | participants | Day 100 |
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| Secondary | Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD) | Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease. | Posted | Number | participants | Day 100 |
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| Secondary | Incidence of Chronic Graft Versus Host Disease (cGVHD) | Chronic graft versus host disease (cGVHD) is a reaction which typically develops 3 to 6 months after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. | Posted | Number | participants | 6 months and 1 year |
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| Secondary | Number of Subjects Alive at 100 Days | Posted | Number | participants | Day 100 |
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| Secondary | Number of Subjects Alive at One Year | Posted | Number | participants | Day 365 |
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| Secondary | Compare Quality of Life (QOL) | PI made decision after IRB approval, but before opening the study to accrual, to not collect QOL data . | Posted | Pretransplant, 1 year, 2 years and 5 years |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 - Matched Sibling Donor | human leukocyte antigen (HLA) genotypic matched sibling donor Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day | 0 | 3 | 2 | 3 | ||
| EG001 | Arm 2 - Matched Unrelated Donor | HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day | 1 | 10 | 10 | 10 | ||
| EG002 | Arm 3 - Mismatched Double Cord Donors | two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord). Stem Cell Transplant: Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Fludarabine, melphalan, ATG or Campath: all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day | 0 | 6 | 6 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Multi-organ failure | General disorders |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Cardiac disorders |
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| Delayed growth | Endocrine disorders |
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| Infection, GI | Infections and infestations |
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| Cystitis | Renal and urinary disorders |
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| Infection, blood | Infections and infestations |
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| Delirious | Psychiatric disorders |
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| Anxiety | Psychiatric disorders |
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| Hallucinations | Psychiatric disorders |
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| Psychosis | Psychiatric disorders |
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| Incipient cataracts, bilateral | Eye disorders |
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| Hearing loss | Ear and labyrinth disorders |
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| Infection, respiratory | Infections and infestations |
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| Pulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders |
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| Infection, skin | Infections and infestations |
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| Acute renal failure | Renal and urinary disorders |
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| GI bleed | Gastrointestinal disorders |
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| Capillary leak | Vascular disorders |
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| Coagulopathy | Blood and lymphatic system disorders |
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| Colonic pneumatosis | Gastrointestinal disorders |
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| Erythrodermic dermatitis | Skin and subcutaneous tissue disorders |
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| Hemolytic anemia | Blood and lymphatic system disorders |
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| Hemorrhagic cystitis | Renal and urinary disorders |
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| Hemorrhagic gastritis | Gastrointestinal disorders |
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| Hyperbilirubinemia | Investigations |
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| Hyperglycemia | Metabolism and nutrition disorders |
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| Hypothyroidism | Endocrine disorders |
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| ICU dementia | Psychiatric disorders |
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| Infection, GU | Infections and infestations |
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| Liver failure | Hepatobiliary disorders |
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| Malnutrition | Metabolism and nutrition disorders |
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| Mucositis | Gastrointestinal disorders |
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| Otitis | Infections and infestations |
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| Pancreatitis | Gastrointestinal disorders |
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| Pericardial effusion | Cardiac disorders |
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| Prerenal azotemia | Metabolism and nutrition disorders |
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| Prolonged QTC interval | Cardiac disorders |
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| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders |
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| Seizure | Nervous system disorders |
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| Skin breakdown | Skin and subcutaneous tissue disorders |
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| Subclavian thrombosis | Vascular disorders |
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| Veno-occlusive disease | Hepatobiliary disorders |
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| Cardiomegaly | Cardiac disorders |
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| Cholestasis portal fibrosis and bile duct proliferation | Hepatobiliary disorders |
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| Ear drainage | Ear and labyrinth disorders |
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| Elevated liver function tests | Investigations |
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| Infection, NOS | Infections and infestations |
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| Intraparenchymal hemorrhage, left frontal lobe | Nervous system disorders |
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| Learning dysfunction | Nervous system disorders |
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| Respiratory distress and apnea | Respiratory, thoracic and mediastinal disorders |
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| Syndrome of inappropriate antidiuretic hormone secretion | Endocrine disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Angela Smith | Masonic Cancer Center, University of Minnesota | 612-626-2778 | smith719@umn.edu |
| ID | Term |
|---|---|
| D051359 | Lymphohistiocytosis, Hemophagocytic |
| D008232 | Lymphoproliferative Disorders |
| D002609 | Chediak-Higashi Syndrome |
| D007153 | Immunologic Deficiency Syndromes |
| D006646 | Histiocytosis, Langerhans-Cell |
| ID | Term |
|---|---|
| D015616 | Histiocytosis, Non-Langerhans-Cell |
| D015614 | Histiocytosis |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000417 | Albinism |
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D010585 | Phagocyte Bactericidal Dysfunction |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D033581 | Stem Cell Transplantation |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D008558 | Melphalan |
| D000961 | Antilymphocyte Serum |
| D000074323 | Alemtuzumab |
| D016572 | Cyclosporine |
| D009173 | Mycophenolic Acid |
| D016756 | Immunoglobulins, Intravenous |
| ID | Term |
|---|---|
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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