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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00025589 | Other Identifier | Johns Hopkins Medicine Institutional Review Board |
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Funding was unavailable to complete the study as originally planned.
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This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.
This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transplant | Experimental | Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine | Drug | Days -6 through -2: 30 mg/m^2 IV daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival | Percentage of participants alive and without relapse or disease progression. | 1 year post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival | Percentage of participants alive with and without relapse. | 2 years post-intervention |
| Overall Survival | Percentage of participants alive. |
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Inclusion Criteria:
Poor-risk CD20+, B-cell lymphoma, as follows:
Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion (if histologic conversion, PR or CR is required):
Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR is required)
Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:
Must have a related donor who is at least HLA haploidentical
Any previous BMT must have occurred at least 3 months prior
Left ventricular ejection fraction at least 35%
Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of normal
FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least 40% of predicted
Absence of uncontrolled infection
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yvette L Kasamon, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26183076 | Result | Kanakry JA, Gocke CD, Bolanos-Meade J, Gladstone DE, Swinnen LJ, Blackford AL, Fuchs EJ, Huff CA, Borrello I, Matsui WH, Brodsky RA, Rosner GL, Shanbhag S, Luznik L, Jones RJ, Ambinder RF, Kasamon YL. Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors. Biol Blood Marrow Transplant. 2015 Dec;21(12):2115-2122. doi: 10.1016/j.bbmt.2015.07.012. Epub 2015 Jul 14. |
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52 participants were screen failures and did not proceed on the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Transplant | Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Cyclophosphamide | Drug | Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily |
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| Total body irradiation | Radiation | Day -1: 200 centigray (cGy) in a single fraction |
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| Tacrolimus | Drug | Start on Day 5 through Day 180 |
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| Mycophenolate Mofetil | Drug | Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) |
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| Rituximab | Drug | Day 30 and every week after for 8 total doses: 375 mg/m^2 IV |
|
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| Allogeneic Bone Marrow Transplant (BMT) | Biological | Day 0: Donor bone marrow infusion |
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| 1 year post intervention |
| Overall Survival | Percentage of participants alive. | 2 years post intervention |
| Relapse | Percentage of participants alive with relapse or disease progression. | 1 year post intervention |
| Relapse | Percentage of participants alive with relapse or disease progression. | 2 years post intervention |
| Non-relapse Mortality | Percentage of participants who died due to BMT-related reasons. | 1 year post intervention |
| Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD) | Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria. | 1 year post intervention |
| Incidence of Grades III-IV Acute GVHD | Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria. | 1 year post intervention |
| Incidence of Chronic GVHD | Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. | 1 year post intervention |
| Engraftment | Percentage of patients who engrafted neutrophils and platelets. | Day 60 |
| Graft Failure | Percentage of participants who failed to engraft. | Day 60 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Transplant | Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV |
| 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, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | 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 | Progression-free Survival | Percentage of participants alive and without relapse or disease progression. | Populations were analyzed as follows:
| Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post-intervention |
|
|
| |||||||||||||||||||||||||||
| Secondary | Progression-free Survival | Percentage of participants alive with and without relapse. | Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants) | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years post-intervention |
|
| ||||||||||||||||||||||||||||
| Secondary | Overall Survival | Percentage of participants alive. | Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants) | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
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| Secondary | Overall Survival | Percentage of participants alive. | Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants) | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years post intervention |
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| Secondary | Relapse | Percentage of participants alive with relapse or disease progression. | Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants) | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
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| ||||||||||||||||||||||||||||
| Secondary | Relapse | Percentage of participants alive with relapse or disease progression. | Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants) | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years post intervention |
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| Secondary | Non-relapse Mortality | Percentage of participants who died due to BMT-related reasons. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
|
| |||||||||||||||||||||||||||||
| Secondary | Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD) | Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
|
| |||||||||||||||||||||||||||||
| Secondary | Incidence of Grades III-IV Acute GVHD | Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
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| |||||||||||||||||||||||||||||
| Secondary | Incidence of Chronic GVHD | Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post intervention |
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| Secondary | Engraftment | Percentage of patients who engrafted neutrophils and platelets. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 60 |
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| Secondary | Graft Failure | Percentage of participants who failed to engraft. | Two participants were not analyzed because they died prior to Day 60. | Posted | Count of Participants | Participants | Day 60 |
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1 year
Adverse events were assessed by the investigator and by labwork at each study visit as per protocol.
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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 | Transplant | Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV | 34 | 83 | 56 | 83 | 62 | 83 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic reaction | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Pancytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Chest pain | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Left ventricular systolic dysfunction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Rigors/chills | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Failure to thrive | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Fever | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Volume overload | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Cholelithiasis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Bleeding | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Liver failure | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
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| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Hyperkalemia | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Hypogammaglobulinemia | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Metabolic acidosis | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hip fracture | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Altered consciousness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Optic neuritis | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Knee pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Respiratory acidosis | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Bronchitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
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| Hemophagocytic syndrome | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
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| Sinusitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Deep vein thrombosis | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Neutropenic fever | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Sinusitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rich Ambinder, MD | Johns Hopkins University | 4109558839 | rambind1@jhmi.edu |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003520 | Cyclophosphamide |
| D014916 | Whole-Body Irradiation |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D018942 | Macrolides |
| D007783 | Lactones |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| 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 |
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| VV donor |
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| VF donor |
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| FF donor |
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