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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-01550 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2007 | |||
| 2007.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This phase II trial studies fludarabine phosphate and total-body irradiation with or without alemtuzumab followed by donor stem cell transplant to see how well it works in treating patients with immunodeficiency or other nonmalignant inherited disorders. Giving chemotherapy, such as fludarabine phosphate, a monoclonal antibody such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining abnormal cells.
PRIMARY OBJECTIVES:
I. Improve donor chimerism levels in patients with inherited nonmalignant disorders undergoing hematopoietic cell transplantation (HCT) using a reduced intensity conditioning regimen either through the addition of Campath (alemtuzumab) or a slightly higher dose of total-body irradiation (TBI).
SECONDARY OBJECTIVES:
I. Decrease the incidence and severity of acute and chronic graft-versus-host disease (GVHD) through use of marrow as the stem cell source and Campath.
II. Assess disease response following HCT.
III. Immune reconstitution following HCT.
IV. Incidence of infections.
V. Overall survival.
VI. Percent of patients with cluster of differentiation (CD)33/CD19 donor chimerism > 50%.
OUTLINE:
CONDITIONING REGIMEN: Patients with no life-threatening viral or fungal infections within 1 month before the planned hematopoietic cell transplantation (HCT) receive alemtuzumab intravenously (IV) over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with hemophagocytic lymphohistiocytosis (HLH), immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0.
HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or orally (PO) 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96.
After completion of HCT, patients are followed up at day 84, at 6, 12, 18 and 24 months post-transplantation, and then once a year for 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, low dose radiation) | Experimental | CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alemtuzumab | Biological | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism | The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism. | At 1 year post transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Number of patients alive at 1 year | 1 year |
| Immune Reconstitution by 1 Year Post Transplant | Number of patients with normal range CD3 at 1 year post transplant |
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Inclusion Criteria:
Primary immunodeficiency disorder or other nonmalignant inherited disease (except aplastic anemia and Fanconi anemia) treatable by allogeneic HCT
Patients with pre-existing medical conditions or other factors that renders them at high risk for regimen related toxicity or ineligible for a conventional myeloablative HCT
Donors: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, -C, and at the allele level for -DRB1 and -DQB1; related donors must be a match or a single allele mismatch at HLA-A, B, and C (at highest resolution available at the time of donor selection) and matched at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing
Donors: Unrelated donors who are prospectively:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lauri Burroughs | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital and Research Center at Oakland | Oakland | California | 94609-1809 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Chemotherapy, Low Dose Radiation) | CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Allogeneic Bone Marrow Transplantation | Procedure | Undergo HCT |
|
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| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo HCT |
|
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| Cyclosporine | Drug | Given PO or IV |
|
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| Fludarabine Phosphate | Drug | Given IV |
|
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| Laboratory Biomarker Analysis | Other | Correlative study |
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| Mycophenolate Mofetil | Drug | Given PO or IV |
|
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| Total-Body Irradiation | Radiation | Undergo low dose TBI |
|
|
| 1 year |
| Disease Response by 1 Year Post Transplant | Number of patients at 1 year with disease response (defined as no clinical evidence of active disease and/or sufficient level of donor chimerisms to prevent disease recurrence) | 1 year |
| Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant | Number of patients who achieve greater than 50% CD33+ donor chimerisms at 1 year post transplant. | 1 year |
| Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant | Number of Patients Who Achieve Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant | 1 year |
| Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant | Number of patients who experienced a clinical significant infection, requiring treatment, within 100 days post transplant. | 100 days |
| Number of Patients Diagnosed With Acute GVHD | Number of patients diagnosed with acute GVHD by Day 100 post transplant | Day 100 |
| Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD | Number of patients diagnosed with overall grade I or grade II acute GVHD by Day 100 post transplant | Day 100 |
| Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD | Number of patients diagnosed with overall Grade III or Grade IV Acute GVHD by Day 100 post transplant | Day 100 |
| Number of Patients Diagnosed With Chronic GVHD | Number of patients diagnosed with chronic GVHD within 1 year post transplant | 1 year |
| Cleveland Clinic Foundation |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53201 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Chemotherapy, Low Dose Radiation) | CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| 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 Patients Who Achieve Greater Than 50% Donor T-cell Chimerism | The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism. | Excludes 9 patients who expired prior to 1 year | Posted | Count of Participants | Participants | At 1 year post transplant |
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| Secondary | Overall Survival | Number of patients alive at 1 year | Excludes 3 patients with graft rejection and second transplant prior to 1 year. | Posted | Count of Participants | Participants | 1 year |
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| |||||||||||||||||||||||||||
| Secondary | Immune Reconstitution by 1 Year Post Transplant | Number of patients with normal range CD3 at 1 year post transplant | Excludes 16 patients: 13 patients who did not achieve 1 year time point (9 expired, 4 went to second transplant) and 3 patients for whom no data was sent at 1 year from external site | Posted | Count of Participants | Participants | 1 year |
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| |||||||||||||||||||||||||||
| Secondary | Disease Response by 1 Year Post Transplant | Number of patients at 1 year with disease response (defined as no clinical evidence of active disease and/or sufficient level of donor chimerisms to prevent disease recurrence) | Excludes 9 patients who expired prior to 1 year time point. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant | Number of patients who achieve greater than 50% CD33+ donor chimerisms at 1 year post transplant. | Excludes 9 patients who expired prior to 1 year time point | Posted | Count of Participants | Participants | 1 year |
|
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| Secondary | Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant | Number of Patients Who Achieve Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant | Excludes 9 patients who expired prior to 1 year time point | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant | Number of patients who experienced a clinical significant infection, requiring treatment, within 100 days post transplant. | Posted | Count of Participants | Participants | 100 days |
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| Secondary | Number of Patients Diagnosed With Acute GVHD | Number of patients diagnosed with acute GVHD by Day 100 post transplant | Posted | Count of Participants | Participants | Day 100 |
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| Secondary | Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD | Number of patients diagnosed with overall grade I or grade II acute GVHD by Day 100 post transplant | Excludes 10 patients who were not diagnosed with acute GVHD | Posted | Count of Participants | Participants | Day 100 |
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| Secondary | Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD | Number of patients diagnosed with overall Grade III or Grade IV Acute GVHD by Day 100 post transplant | Excludes 10 patients who were not diagnosed with acute GVHD | Posted | Count of Participants | Participants | Day 100 |
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| Secondary | Number of Patients Diagnosed With Chronic GVHD | Number of patients diagnosed with chronic GVHD within 1 year post transplant | Excludes 6 patients who expired prior to Day 100 | Posted | Count of Participants | Participants | 1 year |
|
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Day 200 post initiation of conditioning therapy
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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 | Treatment (Chemotherapy, Low Dose Radiation) | CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab IV over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with HLH, IPEX syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0. HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96. Alemtuzumab: Given IV Allogeneic Bone Marrow Transplantation: Undergo HCT Allogeneic Hematopoiet | 9 | 28 | 10 | 28 | 13 | 28 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericardial Effusion | Cardiac disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hyperbilirubinemia | Hepatobiliary disorders | Systematic Assessment |
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| Sepsis | Infections and infestations | Systematic Assessment |
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| Cardiorspiratory Failure | Cardiac disorders | Systematic Assessment |
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| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperbilirubinemia | Hepatobiliary disorders | Systematic Assessment |
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| Hypertension | Cardiac disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fever of Unknown Origin | Infections and infestations | Systematic Assessment |
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| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Secondary Malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Renal Insufficiency | Renal and urinary disorders | Systematic Assessment |
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| Renal Failure, requiring dialysis | Renal and urinary disorders | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
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| Mucositis | Gastrointestinal disorders | Systematic Assessment |
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| Hemolysis | Blood and lymphatic system disorders | Systematic Assessment |
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| Cardiovascular, not otherwise specified | Cardiac disorders | Systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bleeding - Vaginal | Blood and lymphatic system disorders | Systematic Assessment |
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| Bleeding - Lung | Blood and lymphatic system disorders | Systematic Assessment |
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| Bleeding - GI | Blood and lymphatic system disorders | Systematic Assessment |
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| Bleeding - CNS | Blood and lymphatic system disorders | Systematic Assessment |
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| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Lauri Burroughs | Fred Hutch Cancer Research | 206-667-2396 | lburroug@fredhutch.org |
| ID | Term |
|---|---|
| D007153 | Immunologic Deficiency Syndromes |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000074323 | Alemtuzumab |
| D016572 | Cyclosporine |
| D003524 | Cyclosporins |
| C042382 | fludarabine phosphate |
| D009173 | Mycophenolic Acid |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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